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1. Exosomal MALAT1 from macrophages treated with high levels of glucose upregulates LC3B expression via miR-204-5p downregulation

Author: Kou-Gi, Shyu, primary, Wang, Bao-Wei, additional, Pan, Chun-Ming, additional, Fang, Wei-Jen, additional, and Lin, Chiu-Mei, additional
Published: 2024
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2. 2021 Consensus Pathway of the Taiwan Society of Cardiology on Novel Therapy for Type 2 Diabetes

Author: Chern-En Chiang, MD, PhD, Kwo-Chang Ueng, MD, Ting-Hsing Chao, MD, Tsung-Hsien Lin, MD, PhD, Yih-Jer Wu, MD, PhD, Kang-Ling Wang, MD, Shih-Hsien Sung, MD, PhD, Hung-I Yeh, MD, PhD, Yi-Heng Li, MD, PhD, Ping-Yen Liu, MD, PhD, Kuan-Cheng Chang, MD, PhD, Kou-Gi Shyu, MD, PhD, Jin-Long Huang, MD, PhD, Cheng-Dao Tsai, MD, Huei-Fong Hung, MD, Ming-En Liu, MD, Tze-Fan Chao, MD, PhD, Shu-Meng Cheng, MD, PhD, Hao-Min Cheng, MD, PhD, Pao-Hsien Chu, MD, Wei-Hsian Yin, MD, PhD, Yen-Wen Wu, MD, PhD, Wen-Jone Chen, MD, PhD, Wen-Ter Lai, MD, Shing-Jong Lin, MD, PhD, San-Jou Yeh, MD, Juey-Jen Hwang, MD, PhD, and Charles Jia-Yin Hou, MD
Subjects: antidiabetic agents, chronic kidney disease, heart failure, Taiwan Society of Cardiology, type 2 diabetes, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Type 2 diabetes is a major threat to human health in the 21st century. More than half a billion people may suffer from this pandemic disease in 2030, leading to a huge burden of cardiovascular complications. Recently, 2 novel antidiabetic agents, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, reduced cardiovascular complications in a number of randomized control trials. To integrate new information and to achieve a streamlined process for better patient care, a working group was appointed by the Taiwan Society of Cardiology to formulate a stepwise consensus pathway for these therapies to reduce cardiovascular events in patients with type 2 diabetes. This consensus pathway is complementary to clinical guidelines, acting as a reference to improve patient care.
Published: 2021
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3. Cost-effectiveness of statin therapy for secondary prevention among patients with coronary artery disease and baseline LDL-C 70–100 mg/dL in Taiwan

Author: Fang-Ju Lin, Kou-Gi Shyu, I-Chang Hsieh, Wayne Huey-Herng Sheu, Shih-Te Tu, Shoou-Jeng Yeh, Chin-I Chen, Kuo-Cheng Lu, Chia-Chao Wu, Wen-Yi Shau, Timothy J. Inocencio, Yao-Chun Wen, and Hung-I Yeh
Subjects: Statin, Secondary prevention, Low-density lipoprotein cholesterol, Coronary artery disease, Cost-effectiveness analysis, Medicine (General), R5-920
Abstract: Background: The recommended target low-density lipoprotein cholesterol (LDL-C) level for coronary artery disease (CAD) patients has been lowered from 100 to 70 mg/dL in several clinical guidelines for secondary prevention. We aimed to assess whether initiating statin treatment in CAD patients with baseline LDL-C 70–100 mg/dL in Taiwan could be cost-effective. Methods: A Markov model was developed to simulate a hypothetical cohort of CAD patients with a baseline LDL-C level of 90 mg/dL. The incidence and recurrence of MI and stroke related to specific LDL-C levels as well as the statin effect, mortality rate, and health state utilities were obtained from the literature. The direct medical costs and rate of fatal events were derived from the national claims database. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) was calculated, and sensitivity analyses were performed. Results: Moderate-intensity statin use, a treatment regimen expected to achieve LDL
Published: 2020
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4. Observational study of dronedarone in Taiwanese patients with atrial fibrillation

Author: Jiunn-Lee Lin, Tsu-Juey Wu, Ching-Pei Chen, Jung-Cheng Hsu, Kwo-Chang Ueng, Jen-Yuan Kuo, Mien-Cheng Chen, Kuan-Hung Yeh, Kuan-Cheng Chang, Yen-Yu Lu, Kou-Gi Shyu, Ming-Shien Wen, Shih-Ann Chen, Ming-Hsiung Hsieh, Wei-Kung Tseng, An-Ning Feng, Teng-Yao Yang, Wen-Chin Ko, Chi-Wen Cheng, Ju-Chi Liu, and Wen-Ter Lai
Subjects: Medicine (General), R5-920
Abstract: Background/Purpose: Currently, data on the real-world use of dronedarone, an antiarrhythmic drug for atrial fibrillation (AF), are contradictory and often based on patient populations comprised of Caucasians. We prospectively investigated the efficacy and safety of dronedarone and risk factors related to treatment outcomes in a real-world use setting. Methods: The prospective, observational, single-arm, multi-center study included a total of 824 Taiwanese patients with a diagnosis of paroxysmal or persistent AF and receiving dronedarone treatment. Risk factors analysis, efficacy, and safety of dronedarone were assessed with a follow-up of six months. Results: Of the 824 patients enrolled (mean age, 75.3 ± 7.2 years), 95.2% had at least one cardiovascular risk factor. An increase in the proportion of patients with sinus rhythm following treatment was seen (52.1% at baseline vs. 67.4% at 6 months). A decrease in the mean duration of AF episodes (388.4 min vs. 62.3 min) and an increase in total AFEQT (65.4 ± 16.2 vs. 74.0 ± 11.8) were also observed after 6 months of treatment. Females, those under the age of 75, and those with symptomatic AF had higher odds of treatment success. At 6 months, 10.5% of patients reported treatment-related AEs. However, only 0.2% of the AEs were both severe in nature and causally related to dronedarone. Conclusion: This six-month study showed dronedarone to be relatively safe and efficacious and to improve quality-of-life in Taiwanese patients with atrial fibrillation. Odds of treatment success were related to the patient's gender, age, and AF type. Keywords: Atrial fibrillation, Dronedarone, Observational, Safety, Quality of life
Published: 2020
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5. 36-month clinical outcomes of patients with venous thromboembolism

Author: Alexander G.G. Turpie, Alfredo E. Farjat, Sylvia Haas, Walter Ageno, Jeffrey I. Weitz, Samuel Z. Goldhaber, Shinya Goto, Pantep Angchaisuksiri, Gloria Kayani, Renato D. Lopes, Chern-En Chiang, Harry Gibbs, Eric Tse, Peter Verhamme, Hugo ten Cate, Juan Muntaner, Sebastian Schellong, Henri Bounameaux, Paolo Prandoni, Uma Maheshwari, Ajay K. Kakkar, Ab Loualidi, Abdurrahim Colak, Abraham Bezuidenhout, Abu Abdool-Carrim, Addala Azeddine, Adriaan Beyers, Adriaan Dees, Ahmed Mohamed, Ahmet Aksoy, Akihiko Abiko, Akinori Watanabe, Alan Krichell, Alberto Alfredo Fernandez, Alberto Tosetto, Alexey Khotuntsov, Alisha Oropallo, Alison Slocombe, Allan Kelly, Amanda Clark, Amr Gad, Amy Arouni, Andor Schmidt, Andrea Berni, Andres Javier Kleiban, Andrew Machowski, Andrey Kazakov, Angel Galvez, Ann Lockman, Anna Falanga, Anoop Chauhan, Antoni Riera-Mestre, Antonino Mazzone, Armando D'Angelo, Artur Herdy, Atsushi Kato, Ayman Abd Elhamid Ebrahim Mahmoud Salem, Azlan Husin, Barbara Erdelyi, Barry Jacobson, Beatrice Amann-Vesti, Bektas Battaloglu, Benedicte Wilson, Benilde Cosmi, Bergmann Jean Francois, Berremeli Toufek, Beverley Hunt, Bhavesh Natha, Bisher Mustafa, Bonnie Chi Shan Kho, Boulon Carine, Brian Zidel, Brisot Dominique, Brousse Christophe, Bruno Trimarco, Canhua Luo, Carlos Alberto Cuneo, Carlos Jerjes Sanchez Diaz, Carsten Schwencke, Cas Cader, Celal Yavuz, Cesar Javier Zaidman, Charles Lunn, Chau-Chung Wu, Cheng Hock Toh, Chevrier Elisa, Chien-Hsun Hsia, Chien-Lung Huang, Chi-Hang Kevin Kwok, Chih-Cheng Wu, Chi-Hung Huang, Chris Ward, Christian Opitz, Christina Jeanneret-Gris, Chung Yin Ha, Chun-Yao Huang, Claude Luyeye Bidi, Clifford Smith, Cornelia Brauer, Corrado Lodigiani, Couturaud Francis, Cynthia Wu, Daniel Staub, Daniel Theodoro, Daniela Poli, David - Riesco Acevedo, David Adler, David Jimenez, David Keeling, David Scott, Davide Imberti, Desmond Creagh, Desmurs-Clavel Helene, Dirk Hagemann, Dirk Le Roux, Dirk Skowasch, Dmitry Belenky, Dmitry Dorokhov, Dmitry Petrov, Dmitry Zateyshchikov, Domenico Prisco, Dorthe Møller, Dusan Kucera, Ehab M. Esheiba, Elizaveta Panchenko, Elkouri Dominique, Emre Dogan, Emre Kubat, Enrique Diaz Diaz, Eric Wai Choi Tse, Erik Yeo, Erman Hashas, Ernst Grochenig, Eros Tiraferri, Erwin Blessing, Escande Orthlieb Michèle, Esther Usandizaga, Ettore Porreca, Fabian Ferroni, Falvo Nicolas, Félix Ayala-Paredes, Firas Koura, Fitjerald Henry, Franco Cosmi, Frans Erdkamp, Gadel Kamalov, Garcia-Bragado Dalmau, Garrigues Damien, Garry Klein, Gaurand Shah, Geert Hollanders, Geno Merli, Georg Plassmann, George Platt, Germain Poirier, German Sokurenko, Ghassan Haddad, Gholam Ali, Giancarlo Agnelli, Gin Gin Gan, Grace Kaye-Eddie, Gregoire Le Gal, Gregory Allen, Guillermo Antonio Llamas Esperón, Guillot Jean-Paul, Hagen Gerofke, Hallah Elali, Hana Burianova, Hans-Juergen Ohler, Haofu Wang, Harald Darius, Harinder S. Gogia, Harry Striekwold, Hatice Hasanoglu, Hatice Turker, Hendrik Franow, Herbert De Raedt, Herman Schroe, Hesham Salah ElDin, Hesham Zidan, Hiroaki Nakamura, Ho Young Kim, Holger Lawall, Hong Zhu, Hongyan Tian, Ho-Young Yhim, Hun Gyu Hwang, Hyeok Shim, Igor Kim, Igor Libov, Igor Sonkin, Igor Suchkov, Ik-Chan Song, Ilker Kiris, Ilya Staroverov, Irene Looi, Isabel M. De La Azuela Tenorio, Ismail Savas, Ivan Gordeev, Ivo Podpera, Jae Hoon Lee, Jameela Sathar, James Welker, Jan Beyer-Westendorf, Jan Kvasnicka, Jan Vanwelden, JangYong Kim, Jaromira Svobodova, Jaspal Gujral, Javier Marino, Javier Tristan Galvar, Jeannine Kassis, Jen-Yuan Kuo, Jhih-Yuan Shih, JiHyun Kwon, Jin Hyun Joh, Jin Hyun Park, Jin Seok Kim, Jinghua Yang, Jiri Krupicka, Jiri Lastuvka, Jiri Pumprla, Jiri Vesely, Joan Carlos Souto, João Antônio Correa, Johan Duchateau, John Perry Fletcher, Jorge del Toro, Jorge Guillermo Chavez Paez, Jørn Nielsen, Jose Dalmo Araujo Filho, Jose Saraiva, Jose Antonio Diaz Peromingo, Jose Gomez Lara, Jose Luis Fedele, Jose Maria Surinach, Joseph Chacko, Juan Antonio Muntaner, Juan Carlos Álvarez Benitez, Juan Moreno Hoyos Abril, Julian Humphrey, Julio Bono, Junji Kanda, Juree Boondumrongsagoon, Kai Hang Yiu, Kanchana Chansung, Karin Boomars, Kate Burbury, Katsuhiro Kondo, Kemal Karaarslan, Kensuke Takeuchi, Knut Kroeger, Konstantin Zrazhevskiy, Koscál Svatopluk, Kou-Gi Shyu, Kristel Vandenbosch, Kuan-Cheng Chang, Kuan-Ming Chiu, Kubina Jean-Manuel, Kwan Jing Wern, Kwo-Chang Ueng, Lalita Norasetthada, Laure Binet, Lee Ping Chew, Lei Zhang, Leone Maria Cristina, Lidwine Tick, Lilia Beatriz Schiavi, Lily Lee Lee Wong, Lohana Borges, Louis Botha, Luc Capiau, Luc Timmermans, Luciano Eduardo López, Luigi Ria, Luis Manuel Hernandez Blasco, Luis Alberto Guzman, Luis Flota Cervera, Mahe Isabelle, Manuel Monreal Bosch, Manuel de los Rios Ibarra, Manuel Núñez Fernandez, Marc Carrier, Marcelo Raul Barrionuevo, Marco Antonio Alcocer Gamba, Marco Cattaneo, Marco Moia, Margaret Bowers, Mariam Chetanachan, Mario Alberto Berli, Mark Fixley, Markus Faghih, Markus Stuecker, Marlin Schul, Martin Banyai, Martin Koretzky, Martin Myriam, Mary Elizabeth Gaffney, Masao Hirano, Masashi Kanemoto, Mashio Nakamura, Mersel Tahar, Messas Emmanuel, Michael Kovacs, Michael Leahy, Michael Levy, Michael Munch, Michael Olsen, Michel De Pauw, Michel Gustin, Michiel Van Betsbrugge, Mikhail Boyarkin, Miroslav Homza, Modise Koto, Mohamed Abdool-Gaffar, Mohamed Ayman Fakhry Nagib, Mohamed El-Dessoki, Mohamed Khan, Monniaty Mohamed, Moo Hyun Kim, Moon-Hee Lee, Mosaad Soliman, Mostafa Shawky Ahmed, Mostafa Soliman Abd el Bary, Moustafa A. Moustafa, Muhammad Hameed, Muhip Kanko, Mujibur Majumder, Nadezhda Zubareva, Nicola Mumoli, Nik Azim Nik Abdullah, Nisa Makruasi, Nishen Paruk, Nonglak Kanitsap, Norberto Duda, Nordiana Nordin, Ole Nyvad, Olga Barbarash, Orcun Gurbuz, Oscar Gomez Vilamajo, Oscar Nandayapa Flores, Ozcan Gur, Oztekin Oto, Pablo Javier Marchena, Patrick Carroll, Pavel Lang, Peter MacCallum, Peter Baron von Bilderling, Peter Blombery, Petr Jansky, Peuch Bernadette, Philippe De Vleeschauwer, Philippe Hainaut, Piera Maria Ferrini, Piriyaporn Iamsai, Ponchaux Christian, Pongtep Viboonjuntra, Ponlapat Rojnuckarin, Prahlad Ho, Pramook Mutirangura, Rachel Wells, Rafael Martinez, Raimundo Tirado Miranda, Ralf Kroening, Rapule Ratsela, Raquel Lopez Reyes, Raul Franco Diaz de Leon, Raymond Siu Ming Wong, Raz Alikhan, Reinhold Jerwan-Keim, Remedios Otero, Renate Murena-Schmidt, Reto Canevascini, Richard Ferkl, Richard White, Rika Van Herreweghe, Rita Santoro, Robert Klamroth, Robert Mendes, Robert Prosecky, Roberto Cappelli, Rudolf Spacek, Rupesh Singh, Sam Griffin, Sang Hoon Na, Sanjeev Chunilal, Saskia Middeldorp, Satoshi Nakazawa, See Guan Toh, Seinturier Christophe, Selim Isbir, Selma Raymundo, Seng Kiat Ting, Serge Motte, Serir Ozkan Aktogu, Servaas Donders, Seung Ick Cha, Seung-Hyun Nam, Sevestre-Pietri Marie-Antoinette, Shaun Maasdorp, Shenghua Sun, Shenming Wang, Sherif Mohamed Essameldin, Sherif Mohamed Sholkamy, Shintaro Kuki, Shuichi Yoshida, Shunzo Matsuoka, Simon McRae, Simon Watt, Siriwimon Patanasing, Siwe-Nana Jean-Léopold, Somchai Wongkhantee, Soo-Mee Bang, Sophie Testa, Stanislav Zemek, Steffen Behrens, Stephan Dominique, Stuart Mellor, Suaran Singh Gurcharan Singh, Sudip Datta, Sunee Chayangsu, Susan Solymoss, Tamara Everington, Tarek Ahmed Adel Abdel-Azim, Tawatchai Suwanban, Taylan Adademir, Terence Hart, Terriat Béatrice, Thifhelimbilu Luvhengo, Thomas Horacek, Thomas Zeller, Tim Boussy, Tim Reynolds, Tina Biss, Ting-Hsing Chao, Tomas Smith Casabella, Tomoya Onodera, Tontanai Numbenjapon, Victor Gerdes, Vladimir Cech, Vladimir Krasavin, Vladimir Tolstikhin, W.A. Bax, Wagih Fawzy Abdel Malek, Wai Khoon Ho, Walter Pharr, Weihong Jiang, Wei-Hsiang Lin, Weihua Zhang, Wei-Kung Tseng, Wen-Ter Lai, Wilfried De Backer, Wilhelm Haverkamp, Winston Yoshida, Wolfgang Korte, Won Il Choi, Yang-Ki Kim, Yasuhiro Tanabe, Yasushi Ohnuma, Yeung-Chul Mun, Yohan Balthazar, Yong Park, Yoshisato Shibata, Yuriy Burov, Yuriy Subbotin, Zdenek Coufal, Zhenwen Yang, Zhicheng Jing, Zhongqi Yang, Pulmonary Medicine, Clinical Genetics, Internal Medicine, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, ACS - Diabetes & metabolism, VU University medical center, Interne Geneeskunde, MUMC+: MA Alg Interne Geneeskunde (9), and RS: Carim - B04 Clinical thrombosis and Haemostasis
Subjects: History, Anticoagulation, Registry, Polymers and Plastics, SDG 3 - Good Health and Well-being, Deep vein thrombosis, Pulmonary embolism, Hematology, Business and International Management, Industrial and Manufacturing Engineering, Venous thromboembolism
Abstract: BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published
Published: 2023

6. Exosomal MALAT1 Derived from High Glucose-Treated Macrophages Up-Regulates Resistin Expression via miR-150-5p Downregulation

Author: Kou-Gi Shyu, Bao-Wei Wang, Wei-Jen Fang, Chun-Ming Pan, and Chiu-Mei Lin
Subjects: high glucose, macrophage, MALAT1, exosome, miR-1505p, resistin, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a crucial role in the pathophysiological process associated with diabetes-related complications. The effect of high glucose levels on macrophage-derived exosomal MALAT1 is unknown. Therefore, we investigated the molecular regulatory mechanisms controlling exosomal MALAT1 in macrophages under high glucose treatment and the therapeutic target of macrophage-derived exosomal MALAT1 using a balloon injury model of vascular disease in diabetic rats. High glucose (25 mM) significantly increased MALAT1 expression in macrophage-derived exosomes. MALAT1 suppressed miR-150-5p expression in macrophage-derived exosomes under high-glucose conditions. Silencing MALAT1 using MALAT1 siRNA significantly reversed miR-150-5p expression induced by macrophage-derived exosomes. Macrophage-derived exosomes under high-glucose treatment significantly increased resistin expression in macrophages. Silencing MALAT1 and overexpression of miR-150-5p significantly decreased resistin expression induced by macrophage-derived exosomes. Overexpression of miR-150-5p significantly decreased resistin luciferase activity induced by macrophage-derived exosomes. Macrophage-derived exosome significantly decreased glucose uptake in macrophages and silencing MALAT1, resistin or overexpression of miR-150-5p significantly reversed glucose uptake. Balloon injury to the carotid artery significantly increased MALAT1 and resistin expression and significantly decreased miR-150-5p expression in arterial tissue. Silencing MALAT1 significantly reversed miR-150-5p expression in arterial tissue after balloon injury. Silencing MALAT1 or overexpression of miR-150-5p significantly reduced resistin expression after balloon injury. In conclusion, high glucose up-regulates MALAT1 to suppress miR-150-5p expression and counteracts the inhibitory effect of miR-150-5p on resistin expression in macrophages to promote vascular disease. Macrophage-derived exosomes containing MALAT1 may serve as a novel cell-free approach for the treatment of vascular disease in diabetes mellitus.
Published: 2022
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7. Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia

Author: Wen-Pin Cheng, Huey-Ming Lo, Bao-Wei Wang, Su-Kiat Chua, Ming-Jen Lu, and Kou-Gi Shyu
Subjects: AMI, atorvastatin, cardiomyocytes, hypoxia, TRB3, Medicine (General), R5-920
Abstract: TRB3 (tribbles 3), an apoptosis-regulated gene, increases during endoplasmic reticulum stress. Hypoxia can induce inflammatory mediators and apoptosis in cardiomyocytes. However, the expression of TRB3 in cardiomyocyte apoptosis under hypoxia is not thoroughly known. We investigated the regulation mechanism of TRB3 expression and apoptosis induced by hypoxia in cardiomyocytes. Methods: An in vivo model of acute myocardial infarction (AMI) was applied in adult Wistar rats to induce myocardial hypoxia. Rat neonatal cardiomyocytes were subjected to 2.5% O2 to induce hypoxia. Results: The expression of TRB3 was evaluated in cultured rat neonatal cardiomyocytes subjected to hypoxia. Hypoxia significantly enhanced TRB3 protein and mRNA expression. Adding c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA), tumor necrosis factor-α (TNF-α) antibody, and atorvastatin 30 minutes before hypoxia reversed the induction of TRB3 protein. A gel-shift assay showed the DNA-binding activity of growth arrest and DNA damage-inducible gene 153 (GADD153), which increased after hypoxia. Hypoxia increased, whereas the TRB3-mut plasmid, SP600125, and TNF-α antibody abolished the hypoxia-induced TRB3 promoter activity. Hypoxia increased the secretion of TNF-α from cardiomyocytes. Exogenous administration of TNF-α recombinant protein to the cardiomyocytes without hypoxia increased TRB3 protein expression, similar to that observed after hypoxia. Hypoxia-induced cardiomyocyte apoptosis is inhibited by TRB3 siRNA, the TNF-α antibody, and atorvastatin. Atorvastatin reduced the TRB3 expression and cardiomyocyte apoptosis induced by AMI. Hypoxia induces TRB3 through TNF-α, JNK, and the GADD153 pathway. Conclusion: Treatment of atorvastatin inhibits the expression of TRB3 and cardiomyocyte apoptosis induced by AMI and hypoxia.
Published: 2017
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8. 2021 Consensus Pathway of the Taiwan Society of Cardiology on Novel Therapy for Type 2 Diabetes

Author: Charles Jia-Yin Hou, Cheng-Dao Tsai, Kwo-Chang Ueng, Yen-Wen Wu, Kuan-Cheng Chang, Wei-Hsian Yin, Yih-Jer Wu, Ping-Yen Liu, Wen-Jone Chen, Hao-Min Cheng, Chern-En Chiang, Huei-Fong Hung, Kou-Gi Shyu, Shing-Jong Lin, Ming-En Liu, Hung-I Yeh, Tsung-Hsien Lin, Shu-Meng Cheng, San-Jou Yeh, Juey-Jen Hwang, Yi-Heng Li, Tze-Fan Chao, Wen-Ter Lai, Shih-Hsien Sung, Jin-Long Huang, Kang-Ling Wang, Pao-Hsien Chu, and Ting-Hsing Chao
Subjects: medicine.medical_specialty, business.industry, heart failure, Type 2 diabetes, medicine.disease, Human health, Taiwan Society of Cardiology, RC666-701, Diabetes mellitus, Heart failure, Pandemic, medicine, Diseases of the circulatory (Cardiovascular) system, antidiabetic agents, type 2 diabetes, business, Intensive care medicine, chronic kidney disease, Antidiabetic agents
Abstract: Type 2 diabetes is a major threat to human health in the 21st century. More than half a billion people may suffer from this pandemic disease in 2030, leading to a huge burden of cardiovascular complications. Recently, 2 novel antidiabetic agents, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, reduced cardiovascular complications in a number of randomized control trials. To integrate new information and to achieve a streamlined process for better patient care, a working group was appointed by the Taiwan Society of Cardiology to formulate a stepwise consensus pathway for these therapies to reduce cardiovascular events in patients with type 2 diabetes. This consensus pathway is complementary to clinical guidelines, acting as a reference to improve patient care.
Published: 2021

9. Predictors of 1-year outcomes in the Taiwan Acute Coronary Syndrome Full Spectrum Registry

Author: Fu-Tien Chiang, Kou-Gi Shyu, Chiung-Jen Wu, Guang-Yuan Mar, Charles Jia-Yin Hou, Ai-Hsien Li, Ming-Shien Wen, Wen-Ter Lai, Shing-Jong Lin, Chi-Tai Kuo, Chieh Kuo, Yi-Heng Li, and Juey-Jen Hwang
Subjects: acute coronary syndrome, antiplatelet agents, clopidogrel, survival rates, Taiwan, Medicine (General), R5-920
Abstract: Evidence-based guidelines have been formulated for optimal management of acute coronary syndrome (ACS). The Taiwan ACS Full Spectrum Registry aimed to evaluate the ACS management and identify the predictors of clinical outcomes of death/myocardial infarction/stroke 1 year post hospital discharge. Methods: Three thousand and eighty confirmed ACS patients enrolled in this registry were followed up for 1 year at 3-month intervals. Patient data on medical interventions as well as clinical events were recorded and analyzed by descriptive statistics. Results: One-year mortality among patients with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina was 6.1%, 10.1%, and 6.2%, respectively. Use of secondary preventive therapies was suboptimal throughout the follow-up phase, especially dual antiplatelet therapy, which fell from 74.8% patients at discharge to 24.9% patients at 1-year follow-up. The odds of an adverse incidence of death/myocardial infarction/stroke 1 year after discharge was significantly reduced in patients receiving aspirin and clopidogrel for ≥9 months and was consequently higher in patients in whom dual antiplatelet therapy was discontinued or prescribed for
Published: 2014
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10. Chrysin boosts KLF2 expression through suppression of endothelial cell-derived exosomal microRNA-92a in the model of atheroprotection

Author: Kou-Gi Shyu, Wen-Pin Cheng, Bao-Wei Wang, Chun-Ming Pan, Chiu-Mei Lin, Su-Kiat Chua, and Wei-Jen Fang
Subjects: 0301 basic medicine, Neointima, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Medicine (miscellaneous), 030209 endocrinology & metabolism, Pharmacology, medicine.disease, Exosome, Microvesicles, Endothelial stem cell, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, KLF2, microRNA, Medicine, Chrysin, Endothelial dysfunction, business
Abstract: Atherosclerosis and its related clinical complications are the leading cause of death. MicroRNA (miR)-92a in the inflammatory endothelial dysfunction leads to atherosclerosis. Kruppel-like factor 2 (KLF2) is required for vascular integrity and endothelial function maintenance. Flavonoids possess many biological properties. This study investigated the vascular protective effects of chrysin in balloon-injured carotid arteries. Exosomes were extracted from human coronary artery endothelial cell (HCAEC) culture media. Herb flavonoids and chrysin were the treatments in these atheroprotective models. Western blotting and real-time PCRs were performed. In situ hybridization, immunohistochemistry, and immunofluorescence analyses were employed. MiR-92a increased after balloon injury and was present in HCAEC culture media. Chrysin was treated, and significantly attenuated the miR-92a levels after balloon injury, and similar results were obtained in HCAEC cultures in vitro. Balloon injury-induced miR-92a expression, and attenuated KLF2 expression. Chrysin increased the KLF2 but reduced exosomal miR-92a secretion. The addition of chrysin and antagomir-92a, neointimal formation was reduced by 44.8 and 49.0% compared with balloon injury after 14 days, respectively. Chrysin upregulated KLF2 expression in atheroprotection and attenuated endothelial cell-derived miR-92a-containing exosomes. The suppressive effect of miR-92a suggests that chrysin plays an atheroprotective role. Proposed pathway for human coronary artery endothelial cell (HCAEC)-derived exosomes induced by chrysin to suppress microRNA (miR)-92a expression and counteract the inhibitory effect of miR-92a on KLF2 expression in HCAECs. This provides an outline of the critical role of the herbal flavonoid chrysin, which may serve as a valuable therapeutic supplement for atheroprotection.
Published: 2021

11. Familial Hypercholesterolemia in Asia Pacific: A Review of Epidemiology, Diagnosis, and Management in the Region

Author: Kou-Gi Shyu, Ru San Tan, Sanjay Kalra, Hung-I Yeh, Chaicharn Deerochanawong, Brian Tomlinson, and Zhenyue Chen
Subjects: Proband, medicine.medical_specialty, Asia, Asia Pacific, Familial hypercholesterolemia, Review, Disease, 030204 cardiovascular system & hematology, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, Asia pacific, Epidemiology, Internal Medicine, medicine, Humans, China, business.industry, Biochemistry (medical), Australia, medicine.disease, Call to action, Family medicine, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Dyslipidemia, New Zealand
Abstract: Familial hypercholesterolemia (FH) is a common genetic disease that is estimated to affect at least 15 million people in the Asia Pacific region. Affected individuals are at significantly increased risk of premature atherosclerotic cardiovascular disease. A literature review was undertaken to provide an overview of the epidemiology, diagnosis, and management of FH across the region. Currently, epidemiological data relating to FH are lacking across the Asia Pacific. Of the 15 countries and regions considered, locally conducted studies to determine FH prevalence were only identified for Australia, China, India, and Japan. Although practically all national clinical guidelines for dyslipidemia include some commentary on FH, specific guidelines on the management of FH are available for only one third of the countries and regions evaluated. Estimates of current FH diagnosis rates suggest that most affected individuals remain undiagnosed and untreated. Although innovative medications such as proprotein convertase subtilisin/kexin type 9 inhibitors have been approved and are available in most countries and regions considered, they are currently reimbursed in only one quarter. Despite these shortcomings, there is cause for optimism. Early experience with cascade screening in Hong Kong, India, and Vietnam has proven an effective means of identifying family members of probands, as has a reverse screening of family members of children with FH in China. FH registries are gaining momentum across the region, with registries now established in almost half of the countries and regions evaluated. This review concludes with a Call to Action on FH for Asia Pacific to engage healthcare professionals, improve public awareness, and form national FH alliances, comprising all relevant healthcare professional organizations, as a platform to expedite national quality improvement programs in the management of FH.
Published: 2021

12. Cyclic stretching boosts microRNA‐499 to regulate Bcl‐2 via microRNA‐208a in atrial fibroblasts

Author: Ying-Ju Yu, Su-Kiat Chua, Wei-Jen Fang, Chiu-Mei Lin, Bao-Wei Wang, and Kou-Gi Shyu
Subjects: 0301 basic medicine, cycling stretch, adult human atrial fibroblasts, Volume overload, microRNA‐499, Apoptosis, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), In vivo, Muscle Stretching Exercises, microRNA, B‐cell lymphoma 2, Animals, Humans, aortocaval shunt, Luciferase, Heart Atria, Binding site, 3' Untranslated Regions, Chemistry, Myocardium, Original Articles, Cell Biology, Fibroblasts, Rats, Cell biology, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, Proto-Oncogene Proteins c-bcl-2, 030220 oncology & carcinogenesis, Molecular Medicine, RNA Interference, Original Article, microRNA‐208a, Reprogramming, Biomarkers
Abstract: MicroRNAs that modulate transcription can regulate other microRNAs and are also up‐regulated under pathological stress. MicroRNA‐499 (miR‐499), microRNA‐208a (miR‐208a) and B‐cell lymphoma 2 (Bcl‐2) play roles in cardiovascular diseases, such as direct reprogramming of cardiac fibroblast into cardiomyocyte and cardiomyocyte apoptosis. Whether miR208a, miR499 and Bcl‐2 were critical regulators in cardiac fibroblast apoptosis under mechanical stretching conditions in human cardiac fibroblasts‐adult atrial (HCF‐aa) was investigated. Using negative pressure, HCF‐aa grown on a flexible membrane base were cyclically stretched to 20% of their maximum elongation. In adult rats, an aortocaval shunt was used to create an in vivo model of volume overload. MiR208a was up‐regulated early by stretching and returned to normal levels with longer stretching cycles, whereas the expression of miR499 and Bcl‐2 was up‐regulated by longer stretching times. Pre‐treatment with antagomir‐499 reversed the miR‐208a down‐regulation, whereas Bcl‐2 expression could be suppressed by miR‐208a overexpression. In the HCF‐aa under stretching for 1 h, miR‐499 overexpression decreased pri‐miR‐208a luciferase activity; this inhibition of pri‐miR‐208a luciferase activity with stretching was reversed when the miR‐499‐5p binding site in pri‐miR‐208a was mutated. The addition of antagomir‐208a reversed the Bcl‐2‐3′UTR suppression from stretching for 1 h. Flow cytometric analysis revealed that pre‐treatment with miR‐499 or antagomir‐208a inhibited cellular apoptosis in stretched HCF‐aa. In hearts with volume overload, miR‐499 overexpression inhibited myocardial miR‐208a expression, whereas Bcl‐2 expression could be suppressed by the addition of miR‐208a. In conclusion, miR‐208a mediated the regulation of miR‐499 on Bcl‐2 expression in stretched HCF‐aa and hearts with volume overload.
Published: 2021

13. Mechanical stretch via transforming growth factor-β1 activates microRNA-208a to regulate hypertrophy in cultured rat cardiac myocytes

Author: Bao-Wei Wang, Gong-Jhe Wu, Wen-Pin Cheng, and Kou-Gi Shyu
Subjects: cardiac hypertrophy, cardiac myocytes, mechanical stretch, microRNA, transforming growth factor-β1, Medicine (General), R5-920
Abstract: MicroRNA-208a (miR208a) and mechanical stress play a key role in cardiac hypertrophy. The relationship between miR208a and mechanical stress in cultured cardiomyocytes has not been investigated. The molecular mechanisms underlying miR208a-induced hypertrophy of cardiomyocytes by mechanical stress is poorly understood. This study investigated whether miR208a is a critical regulator in cardiomyocyte hypertrophy under mechanical stretch. Methods: Neonatal rat cardiomyocytes grown on a flexible membrane base were stretched at 60 cycles/minute. MiR real-time quantitative assays were used to quantify miRs. A quantitative sandwich enzyme immunoassay technique was used to measure transforming growth factor-β1 (TGF-β1). A 3H-proline incorporation assay was used to measure protein synthesis. Results: Mechanical stretch significantly enhanced miR208a expression. Stretch significantly induced cardiomyocyte hypertrophic protein expression such as β-myosin heavy chain (MHCβ), thyroid hormone receptor-associated protein 100, myostatin, connexin 40, GATA4, and brain natriuretic peptide. MHCα was not induced by stretch. Overexpression of miR208a significantly increased MHCβ protein expression while pretreatment with antagomir208a significantly attenuated MHCβ protein expression induced by stretch and overexpression of miR208a. Mechanical stretch significantly increased the secretion of TGF-β1 from cultured cardiomyocytes. Exogenous addition of TGF-β1 recombinant protein significantly increased miR208a expression and pretreatment with TGF-β1 antibody attenuated miR208a expression induced by stretch. Mechanical stretch and overexpression of miR208a increased protein synthesis while antagomir208a attenuated protein synthesis induced by stretch and overexpression of miR208a. Conclusion: Cyclic stretch enhances miR208a expression in cultured rat cardiomyocytes. MiR208a plays a role in stretch-induced cardiac hypertrophy. The stretch-induced miR208a is mediated by TGF-β1.
Published: 2013
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14. Mechanical Stretch Inhibits MicroRNA499 via p53 to Regulate Calcineurin-A Expression in Rat Cardiomyocytes.

Author: Su-Kiat Chua, Bao-Wei Wang, Li-Ming Lien, Huey-Ming Lo, Chiung-Zuan Chiu, and Kou-Gi Shyu
Subjects: Medicine, Science
Abstract: BackgroundMicroRNAs play an important role in cardiac remodeling. MicroRNA 499 (miR499) is highly enriched in cardiomyocytes and targets the gene for Calcineurin A (CnA), which is associated with mitochondrial fission and apoptosis. The mechanism regulating miR499 in stretched cardiomyocytes and in volume overloaded heart is unclear. We sought to investigate the mechanism regulating miR499 and CnA in stretched cardiomyocytes and in volume overload-induced heart failure.Methods & resultsRat cardiomyocytes grown on a flexible membrane base were stretched via vacuum to 20% of maximum elongation at 60 cycles/min. An in vivo model of volume overload with aorta-caval shunt in adult rats was used to study miR499 expression. Mechanical stretch downregulated miR499 expression, and enhanced the expression of CnA protein and mRNA after 12 hours of stretch. Expression of CnA and calcineurin activity was suppressed with miR499 overexpression; whereas, expression of dephosphorylated dynamin-related protein 1 (Drp1) was suppressed with miR499 overexpression and CnA siRNA. Adding p53 siRNA reversed the downregulation of miR499 when stretched. A gel shift assay and promoter-activity assay demonstrated that stretch increased p53 DNA binding activity but decreased miR499 promoter activity. When the miR499 promoter p53-binding site was mutated, the inhibition of miR499 promoter activity with stretch was reversed. The in vivo aorta-caval shunt also showed downregulated myocardial miR499 and overexpression of miR499 suppressed CnA and cellular apoptosis.ConclusionThe miR499-controlled apoptotic pathway involving CnA and Drp1 in stretched cardiomyocytes may be regulated by p53 through the transcriptional regulation of miR499.
Published: 2016
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15. Tumor Necrosis Factor-Alpha and the ERK Pathway Drive Chemerin Expression in Response to Hypoxia in Cultured Human Coronary Artery Endothelial Cells.

Author: Su-Kiat Chua, Kou-Gi Shyu, Yuh-Feng Lin, Huey-Ming Lo, Bao-Wei Wang, Hang Chang, and Li-Ming Lien
Subjects: Medicine, Science
Abstract: Chemerin, a novel adipokine, plays a role in the inflammation status of vascular endothelial cells. Hypoxia causes endothelial-cell proliferation, migration, and angiogenesis. This study was aimed at evaluating the protein and mRNA expression of chemerin after exposure of human coronary artery endothelial cells (HCAECs) to hypoxia.Cultured HCAECs underwent hypoxia for different time points. Chemerin protein levels increased after 4 h of hypoxia at 2.5% O2, with a peak of expression of tumor necrosis factor-alpha (TNF-alpha) at 1 h. Both hypoxia and exogenously added TNF-alpha during normoxia stimulated chemerin expression, whereas an ERK inhibitor (PD98059), ERK small interfering RNA (siRNA), or an anti-TNF-alpha antibody attenuated the chemerin upregulation induced by hypoxia. A gel shift assay indicated that hypoxia induced an increase in DNA-protein binding between the chemerin promoter and transcription factor SP1. A luciferase assay confirmed an increase in transcriptional activity of SP1 on the chemerin promoter during hypoxia. Hypoxia significantly increased the tube formation and migration of HCAECs, whereas PD98059, the anti-TNF-alpha antibody, and chemerin siRNA each attenuated these effects.Hypoxia activates chemerin expression in cultured HCAECs. Hypoxia-induced chemerin expression is mediated by TNF-alpha and at least in part by the ERK pathway. Chemerin increases early processes of angiogenesis by HCAECs after hypoxic treatment.
Published: 2016
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16. Hyperbaric oxygen‐induced long non‐coding RNA MALAT1 exosomes suppress MicroRNA‐92a expression in a rat model of acute myocardial infarction

Author: Chun-Ming Pan, Chiu-Mei Lin, Bao-Wei Wang, Kou-Gi Shyu, and Wei-Jen Fang
Subjects: Male, 0301 basic medicine, Angiogenesis, Kruppel-Like Transcription Factors, Myocardial Infarction, Infarction, Pharmacology, Exosomes, Exosome, Neovascularization, 03 medical and health sciences, 0302 clinical medicine, microRNA, Animals, exosome, Myocyte, Medicine, Myocytes, Cardiac, Myocardial infarction, Rats, Wistar, Hypoxia, MALAT1, Hyperbaric Oxygenation, Neovascularization, Pathologic, business.industry, Gene Expression Profiling, Myocardium, Hemodynamics, Original Articles, Cell Biology, medicine.disease, Microvesicles, Rats, Platelet Endothelial Cell Adhesion Molecule-1, Disease Models, Animal, MicroRNAs, 030104 developmental biology, Echocardiography, hyperbaric oxygen, 030220 oncology & carcinogenesis, cardiovascular system, Molecular Medicine, RNA, Long Noncoding, Original Article, medicine.symptom, business
Abstract: Hyperbaric oxygen (HBO) improves angiogenesis. The effect of HBO on metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1), a pro‐angiogenic long non‐coding RNA, in cardiac myocyte‐derived exosomes and acute myocardial infarction (AMI) is unknown. We aimed to investigate whether MALAT1 is altered in cardiac myocyte‐derived exosomes in response to HBO as well as the molecular regulatory mechanisms of MALAT1 in cardiac myocytes treated with HBO. Cardiac myocytes were cultured, and HBO was applied at 2.5 atmosphere absolute in a hyperbaric chamber. Exosomes were extracted from the culture media. A rat model of AMI generated by the ligation of the left anterior descending artery was used. HBO significantly increased MALAT1 expression in cardiac myocytes and HBO‐induced MALAT1 and exosomes attenuated miR‐92a expression after myocardial infarction. Expression of krüppel‐like factor 2 (KLF2) and CD31 was significantly decreased after infarction and HBO‐induced exosomes significantly reversed the expression. Silencing of MALAT1 using MALAT1‐locked nucleic acid GapmeR significantly attenuated KLF2 and CD31 protein expression after infarction induced by HBO‐induced exosomes. HBO‐induced exosomes also decreased infarct size significantly. HBO‐induced exosomes from cardiac myocytes up‐regulate MALAT1 to suppress miR‐92a expression and counteract the inhibitory effect of miR‐92a on KLF2 and CD31 expression in left ventricular myocardium after myocardial infarction to enhance neovascularization.
Published: 2020

17. Cost-effectiveness of statin therapy for secondary prevention among patients with coronary artery disease and baseline LDL-C 70–100 mg/dL in Taiwan

Author: Wayne Huey-Herng Sheu, Kou-Gi Shyu, I-Chang Hsieh, Shoou-Jeng Yeh, Hung-I Yeh, Shih-Te Tu, Chin-I Chen, Wen-Yi Shau, Timothy J. Inocencio, Fang-Ju Lin, Chia-Chao Wu, Yao-Chun Wen, and Kuo-Cheng Lu
Subjects: medicine.medical_specialty, Statin, Cost effectiveness, medicine.drug_class, Cost-Benefit Analysis, Taiwan, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Low-density lipoprotein cholesterol, Stroke, health care economics and organizations, lcsh:R5-920, business.industry, Mortality rate, Incidence (epidemiology), Secondary prevention, Cost-effectiveness analysis, General Medicine, Cholesterol, LDL, medicine.disease, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Quality-Adjusted Life Years, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, lcsh:Medicine (General)
Abstract: Background: The recommended target low-density lipoprotein cholesterol (LDL-C) level for coronary artery disease (CAD) patients has been lowered from 100 to 70 mg/dL in several clinical guidelines for secondary prevention. We aimed to assess whether initiating statin treatment in CAD patients with baseline LDL-C 70–100 mg/dL in Taiwan could be cost-effective. Methods: A Markov model was developed to simulate a hypothetical cohort of CAD patients with a baseline LDL-C level of 90 mg/dL. The incidence and recurrence of MI and stroke related to specific LDL-C levels as well as the statin effect, mortality rate, and health state utilities were obtained from the literature. The direct medical costs and rate of fatal events were derived from the national claims database. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) was calculated, and sensitivity analyses were performed. Results: Moderate-intensity statin use, a treatment regimen expected to achieve LDL
Published: 2020

18. Hyperbaric oxygen activates visfatin expression and angiogenesis via angiotensin II and JNK pathway in hypoxic human coronary artery endothelial cells

Author: Bao-Wei Wang, Ying-Ju Yu, Kou-Gi Shyu, and Chiung-Zuan Chiu
Subjects: 0301 basic medicine, Small interfering RNA, medicine.medical_specialty, Angiogenesis, Glucose uptake, adipocytokine, Losartan, 03 medical and health sciences, angiogenesis, 0302 clinical medicine, Cell Movement, Internal medicine, medicine, Humans, RNA, Small Interfering, Receptor, Hypoxia, Nicotinamide Phosphoribosyltransferase, Promoter Regions, Genetic, Cells, Cultured, Tube formation, Anthracenes, Hyperbaric Oxygenation, Neovascularization, Pathologic, Chemistry, Angiotensin II, JNK Mitogen-Activated Protein Kinases, Endothelial Cells, Cell Biology, Original Articles, Hypoxia (medical), Hypoxia-Inducible Factor 1, alpha Subunit, Coronary Vessels, Oxygen, 030104 developmental biology, Endocrinology, Glucose, 030220 oncology & carcinogenesis, hyperbaric oxygen, Molecular Medicine, Cytokines, Original Article, medicine.symptom, medicine.drug, Signal Transduction
Abstract: Visfatin is an adipocytokine with important roles in endothelial angiogenesis. Hyperbaric oxygen (HBO) has been widely used to treat various medical illness with enhanced angiogenesis. The molecular effects of HBO on visfatin under hypoxia are poorly understood. This study aimed to investigate the effect of HBO on visfatin in hypoxic human coronary arterial endothelial cells (HCAECs). HCAECs under chemical hypoxia (antimycin A, 0.01 mmol/L) were exposed to HBO (2.5 atmosphere absolute; ATA) for 2‐4 hours. Western blot, real‐time polymerase chain reaction, electrophoretic mobility shift assay, luciferase promoter activity, migration and tube formation assay, and in vitro glucose uptake were measured. Visfatin protein expression increased in hypoxic HCAECs with earlier angiotensin II (AngII) secretion and c‐Jun N‐terminal kinase (JNK) phosphorylation, which could be effectively suppressed by the JNK inhibitor (SP600125), AngII antibody or AngII receptor blocker (losartan). In hypoxic HCAECs, HBO further induced earlier expression of visfatin and AngII. Hypoxia significantly increased DNA‐protein binding activity of hypoxia‐inducible factor‐1α (HIF‐1α) and visfatin. Hypoxia, hypoxia with HBO and exogenous addition of AngII also increased promoter transcription to visfatin; SP600125 and losartan blocked this activity. In HCAECs, glucose uptake, migration and tube formation were increased in the presence of hypoxia with HBO, but were inhibited by visfatin small interfering RNA, SP600125 and losartan. In conclusion, HBO activates visfatin expression and angiogenesis in hypoxic HCAECs, an effect mediated by AngII, mainly through the JNK pathway.
Published: 2020

19. Observational study of dronedarone in Taiwanese patients with atrial fibrillation

Author: Wen Chin Ko, Teng Yao Yang, Mien Cheng Chen, Jung Cheng Hsu, Ju Chi Liu, Shih Ann Chen, Tsu Juey Wu, Kuan-Cheng Chang, An Ning Feng, Wei Kung Tseng, Chi Wen Cheng, Ching Pei Chen, Ming Shien Wen, Ming Hsiung Hsieh, Wen Ter Lai, Kuan Hung Yeh, Jen Yuan Kuo, Kou Gi Shyu, Kwo Chang Ueng, Jiunn Lee Lin, and Yen Yu Lu
Subjects: Male, medicine.medical_specialty, Treatment outcome, Taiwan, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, Atrial Fibrillation, Humans, Medicine, Sinus rhythm, Prospective Studies, Risk factor, Dronedarone, Aged, Aged, 80 and over, lcsh:R5-920, business.industry, Atrial fibrillation, Mean age, General Medicine, Middle Aged, medicine.disease, Logistic Models, Treatment Outcome, 030220 oncology & carcinogenesis, Quality of Life, Female, 030211 gastroenterology & hepatology, Observational study, lcsh:Medicine (General), business, Anti-Arrhythmia Agents, medicine.drug
Abstract: Background/Purpose: Currently, data on the real-world use of dronedarone, an antiarrhythmic drug for atrial fibrillation (AF), are contradictory and often based on patient populations comprised of Caucasians. We prospectively investigated the efficacy and safety of dronedarone and risk factors related to treatment outcomes in a real-world use setting. Methods: The prospective, observational, single-arm, multi-center study included a total of 824 Taiwanese patients with a diagnosis of paroxysmal or persistent AF and receiving dronedarone treatment. Risk factors analysis, efficacy, and safety of dronedarone were assessed with a follow-up of six months. Results: Of the 824 patients enrolled (mean age, 75.3 ± 7.2 years), 95.2% had at least one cardiovascular risk factor. An increase in the proportion of patients with sinus rhythm following treatment was seen (52.1% at baseline vs. 67.4% at 6 months). A decrease in the mean duration of AF episodes (388.4 min vs. 62.3 min) and an increase in total AFEQT (65.4 ± 16.2 vs. 74.0 ± 11.8) were also observed after 6 months of treatment. Females, those under the age of 75, and those with symptomatic AF had higher odds of treatment success. At 6 months, 10.5% of patients reported treatment-related AEs. However, only 0.2% of the AEs were both severe in nature and causally related to dronedarone. Conclusion: This six-month study showed dronedarone to be relatively safe and efficacious and to improve quality-of-life in Taiwanese patients with atrial fibrillation. Odds of treatment success were related to the patient's gender, age, and AF type. Keywords: Atrial fibrillation, Dronedarone, Observational, Safety, Quality of life
Published: 2020

20. The Efficacy and Safety of Short-Term Tolvaptan Usage in Patients with Acute Decompensated Heart Failure

Author: Yen-Hung, Lin, Cheng-Hsuan, Tsai, Chern-En, Chiang, Jen-Yuan, Kuo, Wei-Hsian, Yin, Ming-Shien, Wen, Ping-Han, Lo, Ping-Yen, Liu, Tsung-Hsien, Lin, Zhih-Cherng, Chen, Kou-Gi, Shyu, Ming-Jui, Hung, Juey-Jen, Hwang, and Chuen-Den, Tseng
Subjects: Original Article
Abstract: BACKGROUND: Patients admitted with acute decompensated heart failure (ADHF) have a poor prognosis and poor quality of life due to dyspnea and edema. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective water diuretic. This study aimed to evaluate the efficacy and safety of a short course of tolvaptan to treat volume overload in patients with ADHF. METHODS: We conducted a phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a short course of tolvaptan (15 mg/day for 4 days) in hospitalized ADHF patients with volume overload despite the use of conventional diuretics. The primary end-point was the change in body weight after 4 days of treatment. The secondary end-points were the change in intake/output balance, change in serum sodium/potassium concentrations, physician/patient assessed signs and symptoms of heart failure after 4 days of treatment, and all-cause mortality in 1 month. RESULTS: A total of 110 patients were screened, and 91 were randomized to receive 15 mg/day of tolvaptan for 4 days (n = 46) or matching placebo (n = 45). Compared to the placebo-treated patients, tolvaptan significantly reduced body weight (-1.36 ± 2.13 kg in the tolvaptan group vs. -0.59 ± 1.27 kg in the placebo group, p = 0.0394). The tolvaptan group also had a negative intake/urine volume balance compared to the placebo group (-509.3 ± 2788.2 ml vs. 975.5 ± 1903.1 ml, p = 0.0059). The safety profile of tolvaptan was acceptable. CONCLUSIONS: Tolvaptan significantly reduced volume overload in hospitalized ADHF patients with volume overload despite the use of conventional diuretics.
Published: 2021

21. Long-term Clinical Outcomes Following Elective Stent Implantation for Unprotected Left Main Coronary Artery Disease

Author: Wei-Syun Hu, Shih-Huang Lee, Chiung-Zuan Chiu, Kou-Gi Shyu, Shen-Chang Lin, Huei-Fong Hung, Jer-Young Liou, and Jun-Jack Cheng
Subjects: coronary artery disease, left main coronary artery, percutaneous coronary intervention, stent, Medicine (General), R5-920
Abstract: Percutaneous coronary intervention (PCI) has been increasingly adopted for unprotected left main coronary artery (LMCA) disease. The aim of this study was to evaluate the predictors of long-term clinical outcomes in patients after elective stent implantation for unprotected LMCA disease. Methods: A total of 122 patients with medically refractory angina who received coronary stenting for unprotected LMCA disease between August 1997 and December 2008 were included. Results: During the follow-up period of 45 ± 35 months (range: 1–137 months), the incidence of repeated PCI and/or coronary artery bypass grafting (CABG), and cardiovascular and total mortality were 28% (34 patients), 20% (24 patients), and 25% (31 patients), respectively. Multivariate analysis revealed that young age [p = 0.02; hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.11–4.30] and bare-metal stent (BMS) use (p = 0.02; HR: 5.35, 95% CI: 1.27–22.57) were the independent predictors of repeated PCI and/or CABG. Only lower left ventricular ejection fraction (LVEF) could predict both cardiovascular mortality (p = 0.003; HR: 4.25, 95% CI: 1.63–11.08) and total mortality (p = 0.002; HR: 3.95, 95% CI: 1.65–9.45). Lower LVEF (p = 0.001; HR: 0.31, 95% CI: 0.16–0.61) and small stent size (p = 0.01; HR: 5.95, 95% CI: 1.43–24.80) could predict the composite endpoint, including target vessel revascularization and total mortality. Conclusion: We showed that young age and BMS implantation could predict repeated PCI and/or CABG after stent implantation for unprotected LMCA disease. Only lower LVEF could predict both cardiovascular and total mortality. Lower LVEF and small stent size but not BMS implantation could predict composite target vessel revascularization/total mortality.
Published: 2011
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22. 2010 Guidelines of the Taiwan Society of Cardiology for the Management of Hypertension

Author: Chern-En Chiang, Tzung-Dau Wang, Yi-Heng Li, Tsung-Hsien Lin, Kuo-Liong Chien, Hung-I Yeh, Kou-Gi Shyu, Wei-Chuen Tsai, Ting-Hsing Chao, Juey-Jen Hwang, Fu-Tien Chiang, and Jyh-Hong Chen
Subjects: blood pressure, disease management, drug therapy, hypertension, Medicine (General), R5-920
Abstract: Hypertension is one of the most important risk factors for atherosclerosis-related mortality and morbidity. In this document, the Hypertension Committee of the Taiwan Society of Cardiology provides new guidelines for hypertension management. The key messages are as follows. (1) The life-time risk for hypertension is 90%. (2) Both the increase in the prevalence rate and the relative risk of hypertension for causing cardiovascular events are higher in Asians than in Caucasians. (3) The control rate has been improved significantly in Taiwan from 2.4% to 21% in men, and from 5% to 29% in women in recent years (1995-2002). (4) Systolic and diastolic blood pressure (BP) = 130/80 mmHg are thresholds of treatment for high-risk patients, such as those with diabetes, chronic kidney disease, stroke, established coronary heart disease, and coronary heart disease equivalents (carotid artery disease, peripheral arterial disease, and abdominal aortic aneurysm). (5) Ambulatory and home BP monitoring correlate more closely with end-organ damage and have a stronger relationship with cardiovascular events than office BP monitoring, but the feasibility of home monitoring makes it a more attractive alternative. (6) Patients with masked hypertension have higher cardiovascular risk than those with white-coat hypertension. (7) Lifestyle changes should be encouraged in all patients, and include the following six items: S-ABCDE (Salt restriction; Alcohol limitation; Body weight reduction; Cessation of smoking; Diet adaptation; Exercise adoption). (8) When pharmacological therapy is needed, physicians should consider “PROCEED” (Previous experience of patient; Risk factors; Organ damage; Contraindication or unfavorable conditions; Expert or doctor judgment; Expense or cost; Delivery and compliance) to decide the optimal treatment. (9) The main benefits of antihypertensive agents are derived from lowering of BP per se, and are generally independent of the drugs being used, except that certain associated cardiovascular conditions might favor certain classes of drugs. (10) There are five major classes of drugs: thiazide diuretics; β-blockers; calcium channel blockers; angiotensin-converting enzyme inhibitors (ACEIs); and angiotensin receptor blockers (ARBs). Any one of these can be used as the initial treatment, except for β-blockers, which are only indicated in patients with heart failure, a history of coronary heart disease, and hyperadrenergic state. (11) A standard dose of any one of the five major classes of antihypertensive drugs can produce an ∼10-mmHg decrease in systolic BP (rule of 10) and a 5-mmHg decrease in diastolic BP (rule of 5), after placebo subtraction. (11) Combination therapy is frequently needed for optimal control of BP, and the amount of the decrease in BP by a two-drug combination is approximately the same as the sum of the decrease by each individual drug (∼20 mmHg in systolic BP and 10 mmHg in diastolic BP) if their mechanisms of action are independent, with the exception of the combination of ACEIs and ARBs. (13) An ACEI or ARB plus a calcium channel blocker or a diuretic (A + C or A + D) are reasonable two-drug combinations, and A+C + D is a reasonable three-drug combination, unless patients have special indications for β-blockers. (14) Single-pill (fixed-dose) combinations that contain more than one drug in a single tablet are highly recommended because they reduce pill burden and cost, and improve compliance. (15) Very elderly patients (> 80 years) should be treated without delay, but BP should be reduced gradually and more cautiously. Finally, these guidelines are not mandatory; the responsible physician's decision remains most important in hypertension management.
Published: 2010
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23. Human Mesenchymal Stem Cells Improve Myocardial Performance in a Splenectomized Rat Model of Chronic Myocardial Infarction

Author: Jen-Fu Liu, Bao-Wei Wang, Huei-Fong Hung, Hang Chang, and Kou-Gi Shyu
Subjects: cellular therapy, mesenchymal stem cells, myocardial infarction, myocardial regeneration, Medicine (General), R5-920
Abstract: Cellular therapy has been applied to animal studies and clinical trials for acute or subacute myocardial infarction. Little is known about the effect of cell therapy on chronic myocardial infarction. The goal of this study was to investigate myocardial performance after human bone marrow-derived mesenchymal stem cell (hMSCs) transplantation in rats with chronic myocardial infarction. Methods: The hMSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of hMSCs were identified by flow cytometry and immunophenotyping. Splenectomy in male rats was performed to prevent immune reaction. One week after splenectomy, ligation of the left anterior descending coronary artery was performed to induce myocardial infarction. Four weeks after ligation of the coronary artery, culture-expanded hMSCs were injected intramyocardially at the left anterior free wall. Left ventricular function measured by echocardiography, infarct size and immunohistochemical stain were performed to evaluate the effect of the therapy. Results: The engrafted hMSCs were positive for the cardiac marker troponin T. Infarct size (35.4 ± 3.4% vs. 53.3 ± 3.0%, p < 0.001) and fibrotic area (2.6 ± 0.1% vs. 5.9 ± 0.2%, p < 0.001) were significantly smaller in the hMSC-treated group than in the control group at 28 days after therapy. hMSC transplantation resulted in smaller left ventricular end-diastolic dimension (6.5 ± 0.1 mm vs. 7.9 ± 0.7 mm, p < 0.001) and better left ventricular ejection fraction (88.7 ± 1.2% vs. 65.8 ± 2.5%, p < 0.001) than in the control group. Capillary density was markedly increased after hMSC transplantation compared with the control group. Conclusion: This study demonstrates that intramyocardial transplantation of hMSCs improves cardiac function after chronic myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium. Transplantation of hMSCs for myocardial regeneration may become the future therapy for chronic myocardial infarction.
Published: 2008
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24. Hypertension Due to Co-existing Paraganglioma and Unilateral Adrenal Cortical Hyperplasia

Author: Kuo-Hsuan Chiang, Jer-Young Liou, Kou-Gi Shyu, Chung-Hsin Yeh, Chin-Chu Wu, Tong-Jong Chen, and Huey-Ming Lo
Subjects: adrenal hyperplasia, hyperaldosteronism, paraganglioma, pheochromocytoma, Medicine (General), R5-920
Abstract: A rare case of combined unilateral adrenal hyperplasia and paraganglioma is reported. A 27-year-old woman presented with hypertension, palpitation, dizziness, and headache for about 3 months. Elevated plasma aldosterone with low renin and a high level of urine vanillylmandelic acid (VMA) were found. Computed tomography showed a microadenoma of the left adrenal gland and a well demarcated left retroperitoneal para-aortic mass. Adrenal vein sampling for aldosterone and renin levels suggested left adrenal lesion. Surgical removal of the left adrenal gland and para-aortic mass was performed. Pathologic examination of the resected left adrenal gland showed adrenal cortical hyperplasia and the left retroperitoneal para-aortic mass showed a paraganglioma. Postoperatively, blood pressure, plasma renin, aldosterone and urine VMA all returned to within normal ranges. The possible relationship of these two diseases is discussed.
Published: 2007
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25. Mechanical Stretch Induces Apoptosis Regulator TRB3 in Cultured Cardiomyocytes and Volume-Overloaded Heart.

Author: Wen-Pin Cheng, Bao-Wei Wang, Huey-Ming Lo, and Kou-Gi Shyu
Subjects: Medicine, Science
Abstract: The expression of TRB3 (tribbles 3), an apoptosis regulated gene, increases during endoplasmic reticulum (ER) stress. How mechanical stress affects the regulation of TRB3 in cardiomyocytes during apoptosis is not fully understood. An in vivo model of aorta-caval shunt in adult rats demonstrated the increased TRB3 protein expression in the myocardium. The tumor necrosis factor-alpha (TNF-α) antagonist etanercept reversed the TRB3 protein expression and cardiomyocyte apoptosis induced by AV shunt. An in vitro model of cyclic stretch in neonatal rats was also used to investigate TRB3 expression. We hypothesized that cardiomyocyte apoptosis induced by cyclic stretch is TRB3 dependent. Neonatal rat cardiomyocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation, at 60 cycles/min. Cyclic stretch significantly increased TRB3 protein and mRNA expression. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125, TNF-α antibody and etanercept 30 min before stretch reversed the induction of TRB3 protein induced by stretch. Cyclic stretch induced the DNA-binding activity of growth arrest and DNA damaged inducible gene-153 (GADD153) by electrophoretic mobility shift assay. SP600125, JNK siRNA, TNF-α antibody and etanercept abolished the binding activity induced by stretch. TRB3 promoter activity was enhanced by stretch and TRB3-mut plasmid, SP600125, TNF-α antibody and etanercept attenuated TRB3 promoter activity induced by stretch. Exogenous administration of TNF-α recombinant protein to the non-stretched cardiomyocytes increased TRB3 protein expression similar to that seen after stretch. Cyclic stretch induced cardiomyocyte apoptosis is inhibited by TRB3 siRNA and etanercept. The stretch-induced TRB3 is mediated by TNF-α、JNK and GADD153 pathway. These results indicate that TRB3 plays an important role in stretch-induced cardiomyocyte apoptosis.
Published: 2015
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26. Change of Scaling-Induced Proinflammatory Cytokine on the Clinical Efficacy of Periodontitis Treatment

Author: Kou-Gi Shyu, Cheuk-Sing Choy, Daniel Chung-Lang Wang, Wei-Chen Huang, Shyuan-Yow Chen, Chien-Hsun Chen, Che-Tong Lin, Chao-Chien Chang, and Yung-Kai Huang
Subjects: Technology, Medicine, Science
Abstract: Proinflammatory cytokines are key inflammatory mediators in periodontitis. This study aimed to investigate the relationship between proinflammatory cytokines in saliva and periodontal status. To investigate the usefulness of cytokines in the therapeutic approach for periodontal disease, the relationship between stimulated cytokine changes and the periodontitis treatment outcome was investigated in this study. Saliva was obtained from 22 patients diagnosed by dentists as having chronic periodontitis. The proinflammatory cytokine (interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), and tumor necrosis factor β (TNF-β)) levels were determined using a commercially available kit. The IL-1β and IL-6 levels increased, whereas the TNF-β levels decreased with the severity of periodontitis (4 mm pocket percentage). Poststimulation IL-1α, IL-6, and IL-8 levels were higher in patients who had an improved treatment outcome. The differences of IL-6 levels (cut point: 0.05 μg/g) yielded a sensitivity and specificity of 90.0% and 81.82%, respectively, for predicting the periodontitis treatment outcome. Among the proinflammatory cytokines, stimulated IL-6 was an excellent marker for predicting the periodontitis treatment outcome.
Published: 2015
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27. Metformin was associated with lower all-cause mortality in type 2 diabetes with acute coronary syndrome: A Nationwide registry with propensity score-matched analysis

Author: I-Chang Hsieh, Wei-Shiang Lin, Chih-Neng Hsu, Jun-Ted Chong, Chih-Cheng Wu, Kwo-Chang Ueng, Kuan-Yu Chen, Wen-Chol Voon, Fang-Ying Su, Mu-Yang Hsieh, Kou-Gi Shyu, Chao-Lun Lai, and Chien-Boon Jong
Subjects: Male, Acute coronary syndrome, medicine.medical_specialty, endocrine system diseases, Population, Taiwan, Type 2 diabetes, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Humans, Hypoglycemic Agents, Medicine, Prospective Studies, Registries, 030212 general & internal medicine, Acute Coronary Syndrome, Mortality, Propensity Score, education, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, business.industry, Proportional hazards model, Mortality rate, Hazard ratio, Middle Aged, medicine.disease, Metformin, Diabetes Mellitus, Type 2, Propensity score matching, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: Background No randomized controlled trials evaluating metformin therapy efficacy in patients with type 2 diabetes mellitus (DM) and acute coronary syndrome (ACS) have been reported. We aimed to examine the mortality benefit of metformin therapy in patients with type 2 DM and ACS, compared with non-metformin anti-diabetes agents users. Methods Data were extracted from the prospective nationwide ACS-DM Taiwan Society of Cardiology registry. Propensity score (PS) matching on baseline characteristics and treatment measures was performed for metformin versus non-metformin users. The Cox proportional hazards model was used to compare mortality outcomes among the PS-matched cohort as the primary analysis. The Cox proportional hazards models adjusting for all pre-determined covariates and quintiles of the PS among the overall population were performed as the secondary analyses. Results Of 1157 patients with type 2 DM and ACS receiving anti-diabetes agents, 78 patients (6.7%) died over the 2-year follow-up period. After PS matching, 318 metformin users were matched with 318 non-metformin users. Metformin users had a lower all-cause mortality rate (adjusted hazard ratio [aHR] 0.50, 95% confidence interval [CI] 0.26–0.95) in the primary analysis. The survival benefit of metformin therapy was consistent in the secondary analyses (aHR 0.30, 95% CI 0.17–0.54 while adjusting for all pre-determined covariates, and aHR 0.34, 95% CI 0.19–0.59 while adjusting for quintiles of the PS). Conclusions Among patients with type 2 DM and ACS, metformin was associated with lower all-cause mortality. However, a detrimental effect of any of the comparators could not be excluded.
Published: 2019

28. Hyperbaric oxygen boosts long noncoding RNA MALAT1 exosome secretion to suppress microRNA-92a expression in therapeutic angiogenesis

Author: Wei-Jen Fang, Chiu-Mei Lin, Bao-Wei Wang, Kou-Gi Shyu, and Chun-Ming Pan
Subjects: Male, Small interfering RNA, Angiogenesis, Blotting, Western, Myocardial Ischemia, Neovascularization, Physiologic, 030204 cardiovascular system & hematology, Exosomes, Real-Time Polymerase Chain Reaction, Exosome, Neovascularization, 03 medical and health sciences, 0302 clinical medicine, microRNA, medicine, Animals, Humans, 030212 general & internal medicine, Therapeutic angiogenesis, Rats, Wistar, Cells, Cultured, Cell Proliferation, Tube formation, Hyperbaric Oxygenation, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Coronary Vessels, Microvesicles, Rats, Disease Models, Animal, MicroRNAs, Cancer research, RNA, RNA, Long Noncoding, Endothelium, Vascular, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Background Hyperbaric oxygen (HBO) could improve wound healing by enhancement of angiogenesis. The effect of HBO on metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a proangiogenic long noncoding RNA, and on endothelial cell-derived exosome is unknown. We aim to investigate both whether MALAT1 is altered in human coronary artery endothelial cells (HCAECs)-derived exosomes in response to HBO as well as the molecular regulatory mechanisms of MALAT1 in HCAECs under HBO treatment. Methods and results HCAECs were cultured and HBO was applied at 2.5 atmosphere absolute (ATA) in a hyperbaric chamber. Exosomes were extracted from culture media. A rat model of hind-limb ischemia was performed by ligation of the right femoral artery. HBO at 2.5 ATA significantly increased MALAT1 expression in HCAECs and HCAECs-derived exosomes. MALAT1 suppressed miR-92a expression in HCAEC-derived exosomes under HBO. Silencing MALAT1 by MALAT1 siRNA significantly inhibited KLF2 mRNA expression induced by HBO, as did MiR-92a. MiR-92a significantly decreased KLF2 luciferase activity in HCAECs under HBO. HBO and HBO-induced exosomes significantly increased cell proliferation and the capillary-like network formation of HCAECs. MALAT1 siRNA and miR-92a overexpression significantly attenuated the cell proliferation and tube formation caused by HBO-induced exosome. HBO and HBO-induced exosomes significantly improved neovascularization in a rat model of hind-limb ischemia. Conclusions HBO upregulates MALAT1 to suppress miR-92a expression and counteracts the inhibitory effect of miR-92a on KLF2 expression in HCAECs to enhance neovascularization. HBO-induced derivation of exosomes from HCAECs enhances angiogenesis. Exosomes containing MALAT1 might serve as a valuable therapeutic tool for neovascularization by HBO.
Published: 2019

29. MicroRNA-208a increases myocardial fibrosis via endoglin in volume overloading heart.

Author: Bao-Wei Wang, Gong-Jhe Wu, Wen-Ping Cheng, and Kou-Gi Shyu
Subjects: Medicine, Science
Abstract: MicroRNA-208a (mir-208a) is essential for cardiac hypertrophy and fibrosis. Endoglin, a co-receptor of transforming growth factor-β is also essential for cardiac fibrosis. Endoglin has been shown to be a target of mir-208a in the in vitro mechanical stress model. Volume overload can lead to heart failure and cardiac fibrosis. The role of mir-208a and endoglin in volume overload heart failure is well known. We sought to investigate the mechanism of regulation of mir-208a and endoglin in volume overload-induced heart failure. Aorta-caval (AV) shunt was performed in adult Sprague-Dawley rats to induce volume overload. Heart weight and heart weight/body weight ratio significantly increased in AV shunt animals. AV shunt significantly increased left ventricular end-diastolic dimension as compared to sham group. Mir-208a was significantly induced by AV shunt from 3 to 14 days. Endoglin, myosin heavy chain-β and brain natriuretic peptide were significantly induced by AV shunt from 3 to 14 days. Overexpression of mir-208a in the sham group without AV shunt significantly increased endoglin expression similar to the AV shunt group. Antagomir-208a attenuated the endoglin expression induced by AV shunt. Pretreatment with atorvastatin also attenuated the endoglin expression induced by AV shunt. AV shunt significantly increased myocardial fibrosis as compared to sham group. Overexpression of mir-208a in the sham group significantly increased myocardial fibrosis. Antagomir-208a and atorvastatin significantly attenuated the myocardial fibrosis induced by AV shunt. In conclusion, mir-208a increased endoglin expression to induce myocardial fibrosis in volume overloaded heart failure. Treatment with atorvastatin can attenuate the myocardial fibrosis induced by volume overload through inhibition of endoglin expression.
Published: 2014
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30. Use of CHADS₂ and CHA₂DS₂-VASc scores to predict subsequent myocardial infarction, stroke, and death in patients with acute coronary syndrome: data from Taiwan acute coronary syndrome full spectrum registry.

Author: Su-Kiat Chua, Huey-Ming Lo, Chiung-Zuan Chiu, and Kou-Gi Shyu
Subjects: Medicine, Science
Abstract: Acute coronary syndrome (ACS) patients have a wide spectrum of risks for subsequent cardiovascular events and death. However, there is no simple, convenience scoring system to identify risk of adverse outcomes. We investigated whether CHADS₂ and CHA₂DS₂-VASc scores were useful tools to assess the risk for adverse events among ACS patients.This observational prospective study was conducted at 39 hospitals. Totally 3,183 patients with ACS were enrolled, and CHADS₂ and CHA₂DS₂-VASc scores were calculated. The primary endpoint was occurrence of adverse event, including subsequent myocardial infarction, stroke, or death, within 1 year of discharge.CHADS₂ and CHA₂DS₂-VASc scores were significant predictors of adverse events in separate multivariate regression analyses. A Kaplan-Meier analysis of CHADS₂ and CHA₂DS₂-VASc scores of ≥2 showed a higher rate of adverse events as compared with scores of
Published: 2014
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31. Effect of atorvastatin on cardiomyocyte hypertrophy through suppressing MURC induced by volume overload and cyclic stretch

Author: Wen-Pin Cheng, Kou-Gi Shyu, Su-Kiat Chua, Huey-Ming Lo, and Bao-Wei Wang
Subjects: Male, 0301 basic medicine, MAPK/ERK pathway, Small interfering RNA, Volume overload, Muscle Proteins, Cardiomegaly, Muscle hypertrophy, 03 medical and health sciences, Arteriovenous Shunt, Surgical, 0302 clinical medicine, MURC, Serum response factor, Animals, Myocytes, Cardiac, Electrophoretic mobility shift assay, Rats, Wistar, Extracellular Signal-Regulated MAP Kinases, cyclic stretch, Chemistry, Kinase, Angiotensin II, Anticholesteremic Agents, volume overload, Original Articles, atorvastatin, Cell Biology, Rats, Cell biology, 030104 developmental biology, Gene Expression Regulation, 030220 oncology & carcinogenesis, Molecular Medicine, Original Article, Stress, Mechanical, Signal Transduction
Abstract: MURC (muscle‐restricted coiled‐coil protein) is a hypertrophy‐related gene. Hypertrophy can be induced by mechanical stress. The purpose of this research was to investigate the hypothesis that MURC mediates hypertrophy in cardiomyocytes under mechanical stress. We used the in vivo model of an aortocaval shunt (AV shunt) in adult Wistar rats to induce myocardial hypertrophy. We also used the in vitro model of cyclic stretch in rat neonatal cardiomyocytes to clarify MURC expression and the molecular regulation mechanism. The flexible membrane culture plate seeding with cardiomyocytes Cardiomyocytes seeded on a flexible membrane culture plate were stretched by vacuum pressure to 20% of maximum elongation at 60 cycles/min. AV shunt induction enhanced MURC protein expression in the left ventricular myocardium. Treatment with atorvastatin inhibited the hypertrophy induced by the AV shunt. Cyclic stretch markedly enhanced MURC protein and mRNA expression in cardiomyocytes. Addition of extracellular‐signal‐regulated kinase (ERK) inhibitor PD98059, ERK small interfering RNA (siRNA), angiotensin II (Ang II) antibody and atorvastatin before stretch, abolished the induction of MURC protein. An electrophoretic mobility shift assay showed that stretch enhanced the DNA binding activity of serum response factor. Stretch increased but MURC mutant plasmid, ERK siRNA, Ang II antibody and atorvastatin reversed the transcriptional activity of MURC induced by stretch. Adding Ang II to the cardiomyocytes also induced MURC protein expression. MURC siRNA and atorvastatin inhibited the hypertrophic marker and protein synthesis induced by stretch. Treatment with atorvastatin reversed MURC expression and hypertrophy under volume overload and cyclic stretch.
Published: 2018

32. Reply to the letter to the Editor 'ECs-derived exosomes: A novel therapeutic target for myocardial ischemia-reperfusion injury'

Author: Bao-Wei Wang, Kou-Gi Shyu, and Chiu-Mei Lin
Subjects: Hyperbaric Oxygenation, Letter to the editor, Myocardial ischemia, business.industry, Hyperbaric oxygenation, Myocardial Reperfusion Injury, medicine.disease, Bioinformatics, Exosomes, Microvesicles, MicroRNAs, Text mining, microRNA, medicine, Humans, RNA, Long Noncoding, Cardiology and Cardiovascular Medicine, business, Reperfusion injury
Published: 2021

33. Chrysin boosts KLF2 expression through suppression of endothelial cell-derived exosomal microRNA-92a in the model of atheroprotection

Author: Chiu-Mei, Lin, Bao-Wei, Wang, Chun-Ming, Pan, Wei-Jen, Fang, Su-Kiat, Chua, Wen-Pin, Cheng, and Kou-Gi, Shyu
Subjects: Flavonoids, MicroRNAs, Kruppel-Like Transcription Factors, Endothelial Cells, Humans
Abstract: Atherosclerosis and its related clinical complications are the leading cause of death. MicroRNA (miR)-92a in the inflammatory endothelial dysfunction leads to atherosclerosis. Krüppel-like factor 2 (KLF2) is required for vascular integrity and endothelial function maintenance. Flavonoids possess many biological properties. This study investigated the vascular protective effects of chrysin in balloon-injured carotid arteries.Exosomes were extracted from human coronary artery endothelial cell (HCAEC) culture media. Herb flavonoids and chrysin were the treatments in these atheroprotective models. Western blotting and real-time PCRs were performed. In situ hybridization, immunohistochemistry, and immunofluorescence analyses were employed.MiR-92a increased after balloon injury and was present in HCAEC culture media. Chrysin was treated, and significantly attenuated the miR-92a levels after balloon injury, and similar results were obtained in HCAEC cultures in vitro. Balloon injury-induced miR-92a expression, and attenuated KLF2 expression. Chrysin increased the KLF2 but reduced exosomal miR-92a secretion. The addition of chrysin and antagomir-92a, neointimal formation was reduced by 44.8 and 49.0% compared with balloon injury after 14 days, respectively.Chrysin upregulated KLF2 expression in atheroprotection and attenuated endothelial cell-derived miR-92a-containing exosomes. The suppressive effect of miR-92a suggests that chrysin plays an atheroprotective role. Proposed pathway for human coronary artery endothelial cell (HCAEC)-derived exosomes induced by chrysin to suppress microRNA (miR)-92a expression and counteract the inhibitory effect of miR-92a on KLF2 expression in HCAECs. This provides an outline of the critical role of the herbal flavonoid chrysin, which may serve as a valuable therapeutic supplement for atheroprotection.
Published: 2020

34. Association of Heart Rate Trajectory Patterns with the Risk of Adverse Outcomes for Acute Heart Failure in a Heart Failure Cohort in Taiwan

Author: Cheng-Chun, Wei, Kou-Gi, Shyu, and Kuo-Liong, Chien
Subjects: Original Article
Abstract: BACKGROUND: Heart rate trajectory with multiple heart rate measurements is considered to be a more sensitive predictor of outcomes than single heart rate measurements. The association of heart rate trajectory patterns with acute heart failure outcomes has not been well studied. We examined the association of heart rate trajectory patterns with post-discharge outcomes. METHODS: This prospective cohort study was based on an acute heart failure registry in Taiwan. A total of 1509 patients were enrolled in the Taiwan Society of Cardiology – Heart Failure with Reduced Ejection Fraction Registry from May 2013 to October 2015. The outcomes were post-discharge all-cause mortality and heart failure re-admission. RESULTS: Two heart trajectory patterns were identified in group-based trajectory analysis. One started with a higher heart rate and had an increasing trend over 6 months then a subsequent decline (high-increasing-decreasing group; n = 352; 23.9%). The other started with a lower heart rate and had a relatively stable pattern (low-stable group; n = 1121; 76.1%). Compared with those in the low-stable group, patients in the high-increasing-decreasing group had a higher risk of events (all-cause mortality: hazard ratio 3.10 and 95% confidence interval 1.24-7.77; heart failure re-admission: hazard ratio 1.13 and 95% confidence interval 0.55-2.32). CONCLUSIONS: Patients with a high-increasing-decreasing heart rate trajectory pattern had a higher risk of all-cause mortality than those with a low-stable pattern.
Published: 2020

35. 2020 Consensus of Taiwan Society of Cardiology on the pharmacological management of patients with type 2 diabetes and cardiovascular diseases

Author: Hao Min Cheng, Juey-Jen Hwang, Jin Long Huang, San Jou Yeh, Cheng Dao Tsai, Hung I. Yeh, Wen-Jone Chen, Ping Yen Liu, Chern En Chiang, Ting-Hsing Chao, Pao-Hsien Chu, Shu Meng Cheng, Yi-Heng Li, Shih Hsien Sung, Kang Ling Wang, Kuan-Cheng Chang, Wen Ter Lai, Yen-Wen Wu, Huei Fong Hung, Tsung-Hsien Lin, Shing Jong Lin, Yih Jer Wu, Ming En Liu, Kwo Chang Ueng, Kou Gi Shyu, Tze Fan Chao, and Wei Hsian Yin
Subjects: medicine.medical_specialty, Consensus, Population, Cardiology, Taiwan, Type 2 diabetes, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Diabetic Nephropathies, education, Stroke, Societies, Medical, Heart Failure, education.field_of_study, business.industry, General Medicine, medicine.disease, Metformin, Clinical trial, Diabetes Mellitus, Type 2, Cardiovascular Diseases, 030220 oncology & carcinogenesis, business, Diabetic Angiopathies, Kidney disease, Cohort study
Abstract: The global incidence and prevalence of type 2 diabetes have been escalating in recent decades. The total diabetic population is expected to increase from 415 million in 2015 to 642 million by 2040. Patients with type 2 diabetes have an increased risk of atherosclerotic cardiovascular disease (ASCVD). About two-thirds of patients with type 2 diabetes died of ASCVD. The association between hyperglycemia and elevated cardiovascular (CV) risk has been demonstrated in multiple cohort studies. However, clinical trials of intensive glucose reduction by conventional antidiabetic agents did not significantly reduce macrovascular outcomes.In December 2008, U.S. Food and Drug Administration issued a mandate that every new antidiabetic agent requires rigorous assessments of its CV safety. Thereafter, more than 200,000 patients have been enrolled in a number of randomized controlled trials (RCTs). These trials were initially designed to prove noninferiority. It turned out that some of these trials demonstrated superiority of some new antidiabetic agents versus placebo in reducing CV endpoints, including macrovascular events, renal events, and heart failure. These results are important in clinical practice and also provide an opportunity for academic society to formulate treatment guidelines or consensus to provide specific recommendations for glucose control in various CV diseases.In 2018, the Taiwan Society of Cardiology (TSOC) and the Diabetes Association of Republic of China (DAROC) published the first joint consensus on the "Pharmacological Management of Patients with Type 2 Diabetes and Cardiovascular Diseases." In 2020, TSOC appointed a new consensus group to revise the previous version. The updated 2020 consensus was comprised of 5 major parts: (1) treatment of diabetes in patients with multiple risk factors, (2) treatment of diabetes in patients with coronary heart disease, (3) treatment of diabetes in patients with stage 3 chronic kidney disease, (4) treatment of diabetes in patients with a history of stroke, and (5) treatment of diabetes in patients with heart failure. The members of the consensus group thoroughly reviewed all the evidence, mainly RCTs, and also included meta-analyses and real-world evidence. The treatment targets of HbA1c were finalized. The antidiabetic agents were ranked according to their clinical evidence. The consensus is not mandatory. The final decision may need to be individualized and based on clinicians' discretion.
Published: 2020

36. Antithrombotic Strategies in Patients with Atrial Fibrillation Following Percutaneous Coronary Intervention: A Systemic Review and Network Meta-Analysis of Randomized Controlled Trials

Author: Huei-Fong Hung, Jun-Jack Cheng, Su-Kiat Chua, Chiung-Zuan Chiu, Kou-Gi Shyu, Chiu-Mei Lin, and Lung-Ching Chen
Subjects: medicine.medical_specialty, medicine.drug_class, triple antithrombotic therapy, medicine.medical_treatment, antithrombotic therapy, lcsh:Medicine, 030204 cardiovascular system & hematology, Article, dual anti-thrombotic therapy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Atrial ﬁbrillation, Randomized controlled trial, law, Internal medicine, Antithrombotic, medicine, atrial fibrillation, 030212 general & internal medicine, Myocardial infarction, Stroke, Aspirin, business.industry, percutaneous coronary intervention, lcsh:R, Percutaneous coronary intervention, General Medicine, Vitamin K antagonist, medicine.disease, Cardiology, business, TIMI, medicine.drug
Abstract: Up to 10% of patients with atrial fibrillation (AF) undergo percutaneous coronary intervention (PCI). A systematic review and network meta-analysis were conducted by searching PubMed, Embase, and the Cochrane database of systematic reviews for randomized control trials that studied the safety and efficacy of different antithrombotic strategies in these patients. Six studies, including 12,158 patients were included. Compared to that in the triple antithrombotic therapy group (vitamin K antagonist (VKA) plus P2Y12 inhibitor and aspirin), thrombolysis in myocardial infarction (TIMI) major bleeding was significantly reduced in the dual antithrombotic therapy (non-vitamin K oral anticoagulants (NOACs) plus P2Y12 inhibitor) group by 47% (Odds ratio (OR), 0.53, 95% credible interval [CrI], 0.35&ndash, 0.78, I2 = 0%). Besides, NOAC plus a P2Y12 inhibitor was associated with less intracranial hemorrhage compared to VKA plus single antiplatelet therapy (OR: 0.20, 95% CrI: 0.05&ndash, 0.77). There was no significant difference in the trial-defined major adverse cardiac events or the individual outcomes of all-cause mortality, cardiovascular death, myocardial infarction, stroke or stent thrombosis among all antithrombotic strategies. In conclusion, antithrombotic strategy of NOACs plus P2Y12 inhibitor is safer than, and as effective as, the strategies including aspirin when used in AF patients undergoing PCI.
Published: 2020

37. (-)-Epigallocatechin Gallate Promotes MicroRNA 145 Expression against Myocardial Hypoxic Injury through Dab2/Wnt3a

Author: Wei-Jen Fang, Sheng-Wen Hou, Kou-Gi Shyu, Chun-Ming Pan, Chiu-Mei Lin, Bao-Wei Wang, and Su-Kiat Chua
Subjects: Myocardial ischemia, Myocardial Ischemia, Gene Expression, 030204 cardiovascular system & hematology, Epigallocatechin gallate, Catechin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Downregulation and upregulation, Wnt3A Protein, microRNA, medicine, Animals, Myocytes, Cardiac, Cells, Cultured, beta Catenin, 030304 developmental biology, 0303 health sciences, Dose-Response Relationship, Drug, General Medicine, Hypoxia (medical), Rats, Adaptor Proteins, Vesicular Transport, MicroRNAs, Complementary and alternative medicine, chemistry, Catenin, Cancer research, medicine.symptom, WNT3A, Phytotherapy
Abstract: MicroRNA 145 (miR-145) is a critical modulator of cardiovascular diseases. The downregulation of myocardial miR-145 is followed by an increase in disabled-2 (Dab2) expression in cardiomyocytes. (-)-epigallocatechin gallate (EGCG) is a flavonoid that has been evaluated extensively due to its diverse pharmacological properties including anti-inflammatory effects. The aim of this study was to investigate the cardioprotective effects of EGCG under hypoxia-induced stress in vitro and in vivo. The hypoxic insult led to the suppression of miR-145 expression in cultured rat cardiomyocytes in a concentration-dependent manner. Western blotting and real-time PCR were performed. In rat myocardial infarction study, in situ hybridization, and immunofluorescent analyses were adopted. The western blot and real-time PCR data revealed that hypoxic stress with 2.5% O2 suppressed the expression of miR-145 and Wnt3a/[Formula: see text]-catenin in cultured rat cardiomyocytes but augmented Dab2. Treatment with EGCG attenuated Dab2 expression, but increased Wnt3a and [Formula: see text]-catenin in hypoxic cultured cardiomyocytes. Following in vivo myocardial infarction (MI) study, the data revealed the myocardial infarct area reduced by 48.5%, 44.6%, and 48.5% in EGCG (50[Formula: see text]mg/kg) or miR-145 dominant or Dab2 siRNA groups after myocardial infarction for 28 days, respectively. This study demonstrated that EGCG increased miR-145, Wnt3a, and [Formula: see text]-catenin expression but attenuated Dab2 expression. Moreover, EGCG ameliorated myocardial ischemia in vivo. The novel suppressive effect was mediated through the miR-145 and Dab2/Wnt3a/[Formula: see text]-catenin pathways.
Published: 2020

38. [Corrigendum] Novel iridium (III)‑derived organometallic compound for the inhibition of human platelet activation

Author: Kou Gi Shyu, Chih Hao Yang, Jiun Yi Li, Duen Suey Chou, Chih Hsuan Hsia, Thanasekaran Jayakumar, Joen Rong Sheu, Chih Wei Hsia, and Marappan Velusamy
Subjects: Published Erratum, Genetics, MEDLINE, Library science, Human platelet, General Medicine
Abstract: After the publication of the above paper, the authors noted that an incomplete version of the address was presented for the second author affiliation; essentially, 'School of Medicine' had been omitted from the address. Therefore, the author and affiliation details for this paper should have been presented as follows: Kou‑Gi Shyu1,2, Marappan Velusamy3, Chih‑Wei Hsia2, Chih‑Hao Yang2, Chih‑Hsuan Hsia2, Duen‑Suey Chou2, Thanasekaran Jayakumar2, Joen‑Rong Sheu2 And Jiun‑Yi Li2,4. 1Division of Cardiology, Shin Kong Wu Ho‑Su Memorial Hospital, Taipei 111; 2Graduate Institute of Medical Sciences and Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan, R.O.C.; 3Department of Chemistry, North Eastern Hill University, Shillong, Meghalaya 793022, India; 4Department of Cardiovascular Surgery, Mackay Memorial Hospital, and Mackay Medical College, Taipei 104, Taiwan, R.O.C. The authors regret that the error with the second author affiliation was not noticed prior to the publication of their paper, and apologize for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 41: 2589‑2600, 2018; DOI: 10.3892/ijmm.2018.3472].
Published: 2019

39. Catalpol Ameliorates Neointimal Hyperplasia in Diabetic Rats

Author: Chiu-Mei Lin, Wei-Jen Fang, Chun-Ming Pan, Sheng-Wen Hou, Bao-Wei Wang, and Kou-Gi Shyu
Subjects: Male, Iridoid Glucosides, Myocardial Ischemia, Pharmaceutical Science, In situ hybridization, Pharmacology, 01 natural sciences, Streptozocin, Analytical Chemistry, Diabetes Mellitus, Experimental, chemistry.chemical_compound, Downregulation and upregulation, Neointima, Drug Discovery, medicine, Animals, Hypoglycemic Agents, Rats, Wistar, Chemokine CCL2, Neointimal hyperplasia, Hyperplasia, biology, 010405 organic chemistry, business.industry, Monocyte, Organic Chemistry, medicine.disease, Streptozotocin, Rehmannia glutinosa, biology.organism_classification, Catalpol, 0104 chemical sciences, Rats, Blot, Rehmannia, 010404 medicinal & biomolecular chemistry, Disease Models, Animal, medicine.anatomical_structure, Carotid Arteries, Complementary and alternative medicine, chemistry, Hyperglycemia, Molecular Medicine, business, Carotid Artery Injuries, medicine.drug
Abstract: Catalpol, an iridoid glycoside, is an isolated natural product of Rehmannia glutinosa, which has been reported to have antidiabetic properties. This study investigated the vascular protective effects of catalpol in hyperglycemic rats with balloon-injured carotid arteries. Balloon injury stress led to the upregulation of monocyte chemoattractant protein-1 expression in rats with streptozotocin-induced diabetes. Western blotting and real-time PCR were performed. In situ hybridization, immunohistochemistry, and confocal analyses were employed. Monocyte chemoattractant protein-1 levels were increased through streptozotocin induction or balloon injury. After treatment with catalpol, the neointimal hyperplasia area was reduced 2 weeks after balloon injury in hyperglycemic rats. Real-time PCR and immunohistochemical analysis demonstrated reduced levels of monocyte chemoattractant protein-1 2 weeks after the balloon injury. Monocyte chemoattractant protein-1 expression was significantly increased in balloon-injured rats compared with the control groups. Thus, treatment with catalpol affected monocyte chemoattractant protein-1 expression. This study demonstrated that catalpol downregulated monocyte chemoattractant protein-1 expression in carotid arteries and ameliorated neointimal hyperplasia in hyperglycemic rats. The suppressive effect of monocyte chemoattractant protein-1 suggests that it plays a key role in neointimal hyperplasia. The results imply that catalpol is potentially effective for preventing hyperglycemia-related ischemic cardiac diseases.
Published: 2019

40. Anticoagulation therapy patterns for acute treatment of venous thromboembolism in GARFIELD-VTE patients

Author: Sylvia Haas, Walter Ageno, Jeffrey I. Weitz, Samuel Z. Goldhaber, Alexander G.G. Turpie, Shinya Goto, Pantep Angchaisuksiri, Joern Dalsgaard Nielsen, Gloria Kayani, Audrey Zaghdoun, Alfredo E. Farjat, Sebastian Schellong, Henri Bounameaux, Lorenzo G. Mantovani, Paolo Prandoni, Ajay K. Kakkar, Ab Loualidi, Abdurrahim Colak, Abraham Bezuidenhout, Abu Abdool‐Carrim, Addala Azeddine, Adriaan Beyers, Adriaan Dees, Ahmed Mohamed, Ahmet Aksoy, Akihiko Abiko, Akinori Watanabe, Alan Krichell, Alberto Alfredo Fernandez, Alberto Tosetto, Alexey Khotuntsov, Alisha Oropallo, Alison Slocombe, Allan Kelly, Amanda Clark, Amr Gad, Amy Arouni, Andor Schmidt, Andrea Berni, Andres Javier Kleiban, Andrew Machowski, Andrey Kazakov, Angel Galvez, Ann Lockman, Anna Falanga, Anoop Chauhan, Antoni Riera‐Mestre, Antonino Mazzone, Armando D'Angelo, Artur Herdy, Atsushi Kato, Ayman Abd Elhamid Ebrahim, Mahmoud Salem, Azlan Husin, Barbara Erdelyi, Barry Jacobson, Beatrice Amann‐Vesti, Bektas Battaloglu, Benedicte Wilson, Benilde Cosmi, Bergmann Jean Francois, Berremeli Toufek, Beverley Hunt, Bhavesh Natha, Bisher Mustafa, Bonnie Chi Shan Kho, Boulon Carine, Brian Zidel, Brisot Dominique, Brousse Christophe, Bruno Trimarco, Canhua Luo, Carlos Alberto Cuneo, Carlos Jerjes Sanchez Diaz, Carsten Schwencke, Cas Cader, Celal Yavuz, Cesar Javier Zaidman, Charles Lunn, Chau‐Chung Wu, Cheng Hock Toh, Chern‐En Chiang, Chevrier Elisa, Chien‐Hsun Hsia, Chien‐Lung Huang, Chi‐Hang Kevin Kwok, Chih‐Cheng Wu, Chi‐Hung Huang, Chris Ward, Christian Opitz, Christina Jeanneret‐Gris, Chung Yin Ha, Chun‐Yao Huang, Claude Luyeye Bidi, Clifford Smith, Cornelia Brauer, Corrado Lodigiani, Couturaud Francis, Cynthia Wu, Daniel Staub, Daniel Theodoro, Daniela Poli, Riesco Acevedo, David Adler, David Jimenez, David Keeling, David Scott, Davide Imberti, Desmond Creagh, Desmurs‐Clavel Helene, Dirk Hagemann, Dirk Le Roux, Dirk Skowasch, Dmitry Belenky, Dmitry Dorokhov, Dmitry Petrov, Dmitry Zateyshchikov, Domenico Prisco, Dorthe Møller, Dusan Kucera, Ehab M. Esheiba, Elizaveta Panchenko, Elkouri Dominique, Emre Dogan, Emre Kubat, Enrique Diaz Diaz, Eric Wai Choi Tse, Erik Yeo, Erman Hashas, Ernst Grochenig, Eros Tiraferri, Erwin Blessing, Escande Orthlieb Michèle, Esther Usandizaga, Ettore Porreca, Fabian Ferroni, Falvo Nicolas, Félix Ayala‐Paredes, Firas Koura, Fitjerald Henry, Franco Cosmi, Frans Erdkamp, Gadel Kamalov, Garcia‐Bragado Dalmau, Garrigues Damien, Garry Klein, Gaurand Shah, Geert Hollanders, Geno Merli, Georg Plassmann, George Platt, Germain Poirier, German Sokurenko, Ghassan Haddad, Gholam Ali, Giancarlo Agnelli, Gin Gin Gan, Grace Kaye‐Eddie, Gregoire Le Gal, Gregory Allen, Guillermo Antonio Llamas Esperón, Guillot Jean‐Paul, Hagen Gerofke, Hallah Elali, Hana Burianova, Hans‐Juergen Ohler, Haofu Wang, Harald Darius, Harinder S. Gogia, Harry Striekwold, Harry Gibbs, Hatice Hasanoglu, Hatice Turker, Hendrik Franow, Herbert De Raedt, Herman Schroe, Hesham Salah ElDin, Hesham Zidan, Hiroaki Nakamura, Ho Young Kim, Holger Lawall, Hong Zhu, Hongyan Tian, Ho‐Young Yhim, Hugo ten Cate, Hun Gyu Hwang, Hyeok Shim, Igor Kim, Igor Libov, Igor Sonkin, Igor Suchkov, Ik‐Chan Song, Ilker Kiris, Ilya Staroverov, Irene Looi, Isabel M De La Azuela Tenorio, Ismail Savas, Ivan Gordeev, Ivo Podpera, Jae Hoon Lee, Jameela Sathar, James Welker, Jan Beyer‐Westendorf, Jan Kvasnicka, Jan Vanwelden, JangYong Kim, Jaromira Svobodova, Jaspal Gujral, Javier Marino, Javier Tristan Galvar, Jeannine Kassis, Jen‐Yuan Kuo, Jhih‐Yuan Shih, JiHyun Kwon, Jin Hyun Joh, Jin Hyun Park, Jin Seok Kim, Jinghua Yang, Jiri Krupicka, Jiri Lastuvka, Jiri Pumprla, Jiri Vesely, Joan Carlos Souto, João Antônio Correa, Johan Duchateau, John Perry Fletcher, Jorge del Toro, Jorge Guillermo Chavez Paez, Jose Dalmo Araujo Filho, Jose Saraiva, Jose Antonio Diaz Peromingo, Jose Gomez Lara, Jose Luis Fedele, Jose Maria Surinach, Joseph Chacko, Juan Antonio Muntaner, Juan Carlos Álvarez Benitez, Juan Moreno Hoyos Abril, Julian Humphrey, Julio Bono, Junji Kanda, Juree Boondumrongsagoon, Kai Hang Yiu, Kanchana Chansung, Karin Boomars, Kate Burbury, Katsuhiro Kondo, Kemal Karaarslan, Kensuke Takeuchi, Knut Kroeger, Konstantin Zrazhevskiy, Koscál Svatopluk, Kou‐Gi Shyu, Kristel Vandenbosch, Kuan‐Cheng Chang, Kuan‐Ming Chiu, Kubina Jean‐Manuel, Kwan Jing Wern, Kwo‐Chang Ueng, Lalita Norasetthada, Laure Binet, Lee Ping Chew, Lei Zhang, Leone Maria Cristina, Lidwine Tick, Lilia Beatriz Schiavi, Lily Lee Lee Wong, Lohana Borges, Louis Botha, Luc Capiau, Luc Timmermans, Luciano Eduardo López, Luigi Ria, Luis Manuel Hernandez Blasco, Luis Alberto Guzman, Luis Flota Cervera, Mahe Isabelle, Manuel Monreal Bosch, Manuel de los Rios Ibarra, Manuel Núñez Fernandez, Marc Carrier, Marcelo Raul Barrionuevo, Marco Antonio Alcocer Gamba, Marco Cattaneo, Marco Moia, Margaret Bowers, Mariam Chetanachan, Mario Alberto Berli, Mark Fixley, Markus Faghih, Markus Stuecker, Marlin Schul, Martin Banyai, Martin Koretzky, Martin Myriam, Mary Elizabeth Gaffney, Masao Hirano, Masashi Kanemoto, Mashio Nakamura, Mersel Tahar, Messas Emmanuel, Michael Kovacs, Michael Leahy, Michael Levy, Michael Munch, Michael Olsen, Michel De Pauw, Michel Gustin, Michiel Van Betsbrugge, Mikhail Boyarkin, Miroslav Homza, Modise Koto, Mohamed Abdool‐Gaffar, Mohamed Ayman Fakhry Nagib, Mohamed El‐Dessoki, Mohamed Khan, Monniaty Mohamed, Moo Hyun Kim, Moon‐Hee Lee, Mosaad Soliman, Mostafa Shawky Ahmed, Mostafa Soliman Abd el Bary, Moustafa A. Moustafa, Muhammad Hameed, Muhip Kanko, Mujibur Majumder, Nadezhda Zubareva, Nicola Mumoli, Nik Azim Nik Abdullah, Nisa Makruasi, Nishen Paruk, Nonglak Kanitsap, Norberto Duda, Nordiana Nordin, Ole Nyvad, Olga Barbarash, Orcun Gurbuz, Oscar Gomez Vilamajo, Oscar Nandayapa Flores, Ozcan Gur, Oztekin Oto, Pablo Javier Marchena, Patrick Carroll, Pavel Lang, Peter MacCallum, Peter Baron von Bilderling, Peter Blombery, Peter Verhamme, Petr Jansky, Peuch Bernadette, Philippe De Vleeschauwer, Philippe Hainaut, Piera Maria Ferrini, Piriyaporn Iamsai, Ponchaux Christian, Pongtep Viboonjuntra, Ponlapat Rojnuckarin, Prahlad Ho, Pramook Mutirangura, Rachel Wells, Rafael Martinez, Raimundo Tirado Miranda, Ralf Kroening, Rapule Ratsela, Raquel Lopez Reyes, Raul Franco Diaz de Leon, Raymond Siu Ming Wong, Raz Alikhan, Reinhold Jerwan‐Keim, Remedios Otero, Renate Murena‐Schmidt, Reto Canevascini, Richard Ferkl, Richard White, Rika Van Herreweghe, Rita Santoro, Robert Klamroth, Robert Mendes, Robert Prosecky, Roberto Cappelli, Rudolf Spacek, Rupesh Singh, Sam Griffin, Sang Hoon Na, Sanjeev Chunilal, Saskia Middeldorp, Satoshi Nakazawa, See Guan Toh, Seinturier Christophe, Selim Isbir, Selma Raymundo, Seng Kiat Ting, Serge Motte, Serir Ozkan Aktogu, Servaas Donders, Seung Ick Cha, Seung‐Hyun Nam, Sevestre‐Pietri Marie‐Antoinette, Shaun Maasdorp, Shenghua Sun, Shenming Wang, Sherif Mohamed Essameldin, Sherif Mohamed Sholkamy, Shintaro Kuki, Shuichi Yoshida, Shunzo Matsuoka, Simon McRae, Simon Watt, Siriwimon Patanasing, Siwe‐Nana Jean‐Léopold, Somchai Wongkhantee, Soo‐Mee Bang, Sophie Testa, Stanislav Zemek, Steffen Behrens, Stephan Dominique, Stuart Mellor, Suaran Singh Gurcharan Singh, Sudip Datta, Sunee Chayangsu, Susan Solymoss, Tamara Everington, Tarek Ahmed Adel Abdel‐Azim, Tawatchai Suwanban, Taylan Adademir, Terence Hart, Terriat Béatrice, Thifhelimbilu Luvhengo, Thomas Horacek, Thomas Zeller, Tim Boussy, Tim Reynolds, Tina Biss, Ting‐Hsing Chao, Tomas Smith Casabella, Tomoya Onodera, Tontanai Numbenjapon, Victor Gerdes, Vladimir Cech, Vladimir Krasavin, Vladimir Tolstikhin, W.A. Bax, Wagih Fawzy Abdel Malek, Wai Khoon Ho, Walter Pharr, Weihong Jiang, Wei‐Hsiang Lin, Weihua Zhang, Wei‐Kung Tseng, Wen‐Ter Lai, Wilfried De Backer, Wilhelm Haverkamp, Winston Yoshida, Wolfgang Korte, Won II Choi, Yang‐Ki Kim, Yasuhiro Tanabe, Yasushi Ohnuma, Yeung‐Chul Mun, Yohan Balthazar, Yong Park, Yoshisato Shibata, Yuriy Burov, Yuriy Subbotin, Zdenek Coufal, Zhenwen Yang, Zhicheng Jing, Zhongqi Yang, Haas, S, Ageno, W, Weitz, J, Goldhaber, S, Turpie, A, Goto, S, Angchaisuksiri, P, Dalsgaard Nielsen, J, Kayani, G, Zaghdoun, A, Farjat, A, Schellong, S, Bounameaux, H, Mantovani, L, Prandoni, P, and Kakkar, A
Subjects: Male, pulmonary embolism, Time Factors, Deep vein, direct oral anticoagulant, Practice Patterns, 030204 cardiovascular system & hematology, heparin, Direct oral anticoagulants, 0302 clinical medicine, Pregnancy, Deep vein thrombosis, 80 and over, Registries, Practice Patterns, Physicians', ddc:616, Aged, 80 and over, Venous Thrombosis, Anticoagulant, Hematology, Heparin, Middle Aged, Thrombosis, Pulmonary embolism, medicine.anatomical_structure, Treatment Outcome, Practice Guidelines as Topic, Female, Guideline Adherence, medicine.drug, medicine.medical_specialty, medicine.drug_class, venous thromboembolism, direct oral anticoagulants, deep vein thrombosis, Aged, Anticoagulants, Blood Coagulation, Drug Utilization, Healthcare Disparities, Humans, Pulmonary Embolism, Venous Thromboembolism, 03 medical and health sciences, Thromboembolism, Internal medicine, medicine, In patient, cardiovascular diseases, Rivaroxaban, Physicians', business.industry, deep vein thrombosi, deep vein thrombosis, direct oral anticoagulants, heparin, pulmonary embolism, venous thromboembolism, equipment and supplies, Venous, medicine.disease, business, Venous thromboembolism
Abstract: Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.
Published: 2019

41. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

Author: Deepak L Bhatt, Philippe Gabriel Steg, Shamir R Mehta, Lawrence A Leiter, Tabassome Simon, Kim Fox, Claes Held, Marielle Andersson, Anders Himmelmann, Wilhelm Ridderstråle, Jersey Chen, Yang Song, Rafael Diaz, Shinya Goto, Stefan K James, Kausik K Ray, Alexander N Parkhomenko, Mikhail N Kosiborod, Darren K McGuire, Robert A Harrington, Vladimir Santos, Ashit Jain, Irina Lendel, Michael Russo, W H Haught, Manuel Bouza, Harinder Gogia, Supratim Banerjee, George Kichura, Louis Kantaros, Francisco Padron, Rakesh Passi, Jay Stone, Michael Pursley, Michael D'Urso, Timothy Gardner, James Bennett, Khaled Nour, Satinder Saini, Wenwu Zhang, Dharam Kumbhani, Dustin Thomas, Dominick Angiolillo, Barry Bertolet, Amaury Roman-Miranda, Robert Black, Ramin Manshadi, Carlos Vaca, Antonio Blanco, Mark Napoli, David Brabham, Ayim Akyea-Djamson, Pratik Desai, Sudhir Prasada, Ajit Khaira, Leslie Forgosh, Ira Lieber, Guillermo Umpierrez, Dinesh Singal, Juan Londono, Neil Fraser, Jose Ruiz, Damaris Vega, Lilia Rodriguez, Christopher Brown, Faizullah Syed, Guarav Aggarwala, William Eaves, Michael Foster, Dinesh Gupta, David Avino, Wail Asfour, Glen Tonnessen, Xue-Qiao Zhao, Narendra Singh, Andrew Brockmyre, Norman Lepor, Nicolas Shammas, David Blick, Steven Hearne, John Prodafikas, Edgar Carell, Mark Izzo, Amin Karim, Bosh Zakhary, Mahmoud Atieh, Steven Leichter, Charles Meadows, David Hotchkiss, Mazen Abu-Fadel, Alan Wiseman, Jeffrey Bander, Mahesh Shah, Subhash Banerjee, Ricky Ganim, Karen Sopko, Misal Khan, Ramon Lloret, Troy Weirick, Rajendra Mehta, Udho Thadani, Anuj Bhargava, Mikhail Kosiborod, Jaynier Moya, Cezar Staniloae, Yamirka D Guerra, Anil Chhabra, Douglas Kosmicki, Wassim Shaheen, Akber Mohammed, J'Cinda Bitters, Jan Pattanayak, Julian Javier, Sunny Srivastava, Roland Phillips, Jessie Al-Amin, Michael Lillestol, Patrick Simpson, Lydie Hazan, Amit Amin, Gopi Shah, Denes Korpas, Bruce Platt, Jim Dickert, Orlando Puente, Louis Hiotis, Timothy Doyle, Raj Rajan, Alan Meholick, Christian Gring, Elie Hage-Korban, Robert Feldman, Harry Colfer, Samuel Butman, Malcolm Foster, Terence Hart, Randall Huling, Shervin Eshaghian, Ofsman Quintana, Deanna Cheung, Franklin Handel, Mara Rodriguez, David Suh, Paul Gordon, Gregg Pressman, Michael Bauer, William French, Mark Barettella, Sridhar Chatrathi, Damodhar Suresh, Ronald Goldberg, Mark Huth, Liwa Younis, Aref Rahman, Richard Mascolo, Michelle Welch, Randeep Suneja, Stephen Smith, Scott Shurmur, John Agaiby, Ahmad Jingo, Janice Johnston, Mary Beth, Anthony Vlastaris, Susan Kemp, Hamid Taheri, Edward Pereira, Michael Deyoung, Zafir Hawa, Ray Smith, Thomas Galski, Samer Garas, M Reddy, Susheel Sharma, Joeseph Hargrove, Charles Treasure, Ronald Emerson, Tariq Haddad, Kathryn Rohr, Larry Levinson, Raul Gaona, Barry Uretsky, Hiralal Maheshwari, Denny Lee, Stephanie Kinnaman, Robert Singal, Jeffrey Geohas, Osvaldo Gigliotti, Ajit Raisinghani, Charanjit Khurana, Brent Hella, Michael Kelberman, Steven Voyce, Sanjay Singh, Eric Lo, Pradeep Singh, Ross Goodfellow, Stuart Fischer, Richard Lorraine, Traci Turner, Jeffrey Shanes, Robert Busch, Robert Broker, Michelle Zaniewski, Kevin Pounds, Giselle Debs-Perez, Stephen Ong, Brad Frandsen, Douglas Fullington, Naseem Jaffrani, Ahtaram Khan, Marcus Lee, Joe Pouzar, George Revtyak, Julian Gonzalez, Samer Nakhle, Abel Murillo, Douglas Young, Sashi Makam, Mushtaq Syed, Kevin Woolf, Paul Grena, Sarab Alfata, Sharan Mahal, David Hoffman, Tinoy Kizhakekuttu, Joseph Deering, Janak Bhavsar, Scott Mikesell, William Wilson, Vance Wilson, Salah El, Francis Spinale, Vinod Kannarkat, Sunder Rao, Lenita Hanson, John Bertsch, Elena Gonzalez-Ortiz, Norma Severino, John Willis, Joel Schock, Ladan Bakhtari, Raul Gazmuri, Saadat Ansari, Jason Hall, Arvind Mehta, Neal Shealy, Stuart Zarich, Deovrat Singh, Kishor Vora, Nabil Andrawis, Darron Molter, David Maron, Jose Cardona, Ronald D'Agostino, Tamjeed Arshad, Rodney Samaan, David Jones, Dale Presser, John Heath, Sandy Green, George Bittar, Sheldon Henry, David Korn, John Schmedtje, Venkatesh Nadar, Bruce Graham, Ajay Labroo, Leonardo Clavijo, Hal Roseman, Gilbert Ledesma, Robert Rosen, Isaac Dor, William Kirby, Jennefer Sutton, Frank Eder, Bruce Iteld, Jose Gomez-Cortes, Maurice Buchbinder, Joseph Kasper, Antonio Terrelonge, Gustavo Torres, Ted Jagielo, Jose Alvarez, Yehuda Handelsman, Mario Guillen, Randall Richwine, Lorena Lewy-Alterbaum, Clinton Corder, Moogali Arvind, David Bolshoun, Magdy Mikhail, Stephen Minton, Odilon Alvarado, J Abbott, Brett Cauthen, Ryan Welter, Randy Mintz, John Cox, Annette Quick, Melvin Weiss, Johnny Dy, James Zebrack, Glenn Gandelman, Vinayak Hegde, Marc Silver, Michele DeGregorio, William Lawson, Christopher Paa, Anna Bortnick, Merrill Krolick, Rodolfo Sotolongo, Jorge Cheirif, Priya Kumar, Preetham Jetty, Ambar Patel, Mariusz Kruk, Iwona Kobielusz-Gembala, Barbara Rewerska, Adam Madrzejewski, Krzysztof Milewski, Jerzy Cygler, Joanna Petryka-Mazurkiewicz, Waldemar Jastrzebski, Janusz Korecki, Wojciech Fil, Janusz Prokopczuk, Anna Bochenek, Marek Wujkowski, Robert Witek, Piotr Konczakowski, Pawel Miekus, Marcin Szczasny, Wlodzimierz Musial, Krzysztof Cymerman, Jacek Lampart, Jacek Mikosinski, Slawomir Szynal, Issa Fares, Grzegorz Opolski, Stanislaw Mazur, Beata Wozakowska-Kaplon, Renata Bijata-Bronisz, Lukasz Wierucki, Beata Losa, Grzegorz Drelich, Marek Konieczny, Pawel Starczewski, Lidia Pawlowicz, Pawel Jesionowski, Jaroslaw Jurowiecki, Jacek Gniot, Mariusz Czyzycki, Karol Stania, Izabela Kucharczyk-Bauman, Benita Busz-Papiez, Agnieszka Karczmarczyk, Wanda Sudnik, Alina Koszek, Piotr Kolodziej, Bartosz Skwarna, Nicolás Jaramillo, Maciej Jankowski, Wojciech Czochra, Leszek Kinasz, Beata Miklaszewicz, Teresa Stasinska, Wladyslaw Pluta, Marcin Basiak, Teresa Rusicka, Izabela Niedbal-Yahfouf, Grazyna Popenda, Romuald Korzeniak, Agnieszka Mirek, Rafal Mariankowski, Lukasz Wojnowski, Marek Korol, Jacek Baszak, Piotr Podolec, Wojciech Piesiewicz, Aleksander Zurakowski, Carlos Luengas, Marek Skura, Piotr Pilecki, Piotr Majchrzak, Ewa Krzyzagórska, Marcin Drozd, Barbara Kaczmarek, Teresa Sliwinska, Katarzyna Zelazowska, Rafal Sztembis, Katarzyna Landa, Lidia Matyszczak-Toniak, Krzysztof Strojek, Marek Piepiorka, Robert Malinowski, Maria Górska, Edyta Stolarczyk-Sowa, Leszek Romanowski, Elzbieta Zinka, Zygfryd Reszka, Joanna Skierkowska, Anna Uzunow, Ewa Laskowska-Derlaga, Ekaterina Puntus, Elena D Kosmacheva, Natalia Koziolova, Prokhor Pavlov, Tatiana Supryadkina, Yury Didenko, Philipp Kopylov, Andrei Kazakov, Sergei Aksentiev, Elena Vishneva, Alexey Repin, Olga Smolenskaya, Olga Mantserova, Oleg Khrustalev, Elena Privalova, Vladimir Konstantinov, Svetlana Boldueva, Andrey Ezhov, Alexander Chernyavsky, Gadel Kamalov, Albert Galyavich, Galina Zubeeva, Galina Nechaeva, Sergey Shustov, Nino Dzhaiani, Tatiana Treshkur, Nataliya Osokina, Alexey Panov, Elena Shutemova, Valeriy Makukhin, Tatiana Kropotina, Larisa Tsyba, Yuri Karpov, J M Sizova, Marina Ballyuzek, Nikolay Tarasov, Elena Demchenko, Olga Barbarash, Valentin Moiseev, Valentin Markov, Vadim Kuznetsov, Inna Viktorova, Igor Sergienko, Lyudmila Ermoshkina, Niyaz Khasanov, Tatiana Khlevchuk, Andrey Baglikov, Sergey Shalaev, Elena Zonova, Elena Reznik, Larisa Haisheva, Tatyana Morugova, Nikita Lomakin, Alexander Vishnevsky, Yuri Shvarts, Olga Magnitskaya, Marina Mikhailusova, Elena Pavlysh, Igor Libov, Anna Zateyschikova, Victor Kostenko, Anton Edin, Yaroslava Khovaeva, Konstantin Zakharov, Raisa Stryuk, Vladimir Khirmanov, Sergey Kanorskiy, Sergey Yakushin, Anna Barabashkina, Hongwei Li, Qiang Zhao, Jian Zhang, Jianhua Ma, Yong He, Ming Luo, Aidong Zhang, Ningru Zhang, Yingru Chai, Genshan Ma, Hao Wang, Zhigang Liu, Lanjie He, Zhifang Song, Xiaolin Dong, Liang Tao, Zhanquan Li, Xi Su, Xiangqing Kong, Heping Niu, Junbo Ge, Zhurong Luo, Wenjun Huang, Daoquan Peng, Zuyi Yuan, Maria Milanova, Doncho Tenev, Antoni Gogov, Dimitar Karageorgiev, Todor Kolchev, Nikolay Rusev, Nikolina Georgieva, Rumen Kondov, Veselin Rusinov, Ivo Petrov, Georgi Stanchev, Mariana Konteva, Adriana Dincheva, Zdravka Yaneva, Ralitsa Vatova, Katya Ilieva, Nikolai Runev, Borislav Kolomanov, Ivan Petrov, Nikolay Iliev, Snezhanka Tisheva, Boryana Chompalova, Maria Tokmakova, Dimitar Raev, Kolyo Byanov, Dimitar Markov, Lenko Mihov, Atanas Mihov, Nora Milcheva, Milen Minchev, Mihail Mollov, Borislav Borisov, Tihomir Tihchev, Venelin Karakolev, Bojidar Dimov, Svetoslav Georgiev, Lachezar Smilov, Bon K Koo, Taehoon Ahn, Soon J Hong, Junghan Yoon, Seok K Oh, Myung H Jeong, Doo-Il Kim, Kiyuk Chang, Weon Kim, Joo-Yong Hahn, Kwang S Cha, Jung-Hee Lee, Si-Wan Choi, Chang-Wook Nam, In-Ho Chae, Yong H Park, Seung-Jea Tahk, Won-Yong Shin, Jei-Keon Chae, Byung J Kim, Jang-Whan Bae, Woo J Park, Seung W Rha, Young J Choi, Jin-Yong Hwang, Hun S Park, Luciano Baracioli, Fabio Guimaraes, Eduardo Vasconcellos, José Saraiva, Adamastor Pereira, Queulla Santos, Paulo Rossi, Lilia Maia, Miguel Madeira, Marcio Pereira, Roberto Botelho, Gilmar Reis, Freddy Eliaschewitz, Joao Borges, Carlos Nascimento, Jose A Fortes, Weimar de Souza, Pedro Pimentel, Miguel Hissa, Marcos Franchetti, Dalton Precoma, Costantino Ortiz, Mauro Hernandes, Wladmir Saporito, Fabio R dos Santos, Adrian Kormann, Fernando Neuenschwander, Oscar Dutra, Nelson Rassi, Luiz Tanajura, Juliana Souza, Delcio S Junior, Paulo Leaes, Adriana Forte, Teresa C Bonansea, Jose Marin, Bruno Machado, Maria J Cerqueira, Frederico Silva, Yorghos Michalaros, Euler Manenti, Cintia Cercato, Estevao Figueiredo, Ming-En Liu, Yi-Chih Wang, Tsung-Ming Lee, Chih Fang, Yen-Wen Wu, Kwo-Chang Ueng, Huey-Herng Sheu, Wen T Lai, I-Chang Hsieh, Zhih-Cherng Chen, Mu-Jang Lee, Chern Chiang, Kou-Gi Shyu, Chien-Hsun Hsia, Guang-Yuan Mar, Shih-Hung Chan, Chih-Cheng Wu, Wei-Kung Tseng, Kuan-Cheng Chang, Hung-I Yeh, Ji-Hung Wang, Charles Hou, Inna Sorokina, Maryna Dolzhenko, Olha Horoshko, Oleksandr Karpenko, Leonid Rudenko, Igor Vakaliuk, Anna Kulyk, Olena Levchenko, Oleksandr Prokhorov, Dmytro Reshotko, Mykhaylo Sorokivskyy, Nataliia Velichko, Valentyn Maslovskyi, Zinaida Teliatnikova, Sergiy Dotsenko, Olena Krakhmalova, Igor Kraiz, Viktoria Zharinova, Larysa Bula, Igor Kaydashev, Valeriy Molodtsov, Lesya Rasputina, Viktoriya Pidlisna, Olena Lysunets, Anatoliy Kravchenko, Liubomyr Glushko, Tetyana Khomazyuk, Yevgeniya Svyshchenko, Oleksandr Parkhomenko, Boris Mankovsky, Orest Abrahamovych, Andriy Yagensky, Mykola Stanislavchuk, Larisa Vasilyeva, Liubov Sokolova, Oleg Sychov, Vira Tseluyko, Igor Kyrychenko, Mykola Rishko, Sergiy Furkalo, Richard Gallo, Olivier Bertrand, Shamir Mehta, Christian Constance, Bruce Sussex, Remo Zadra, Simon Kouz, Raja Chehayeb, Amritanshu Pandey, Danielle Dion, Gordon Bailey, Laurie Hill, Krishnan Ramanathan, Micha Dorsch, Alykhan Nanji, Mohan Babapulle, Martine Montigny, Gilbert Gosselin, Payam Dehghani, Dennis Rupka, Michel Le May, Francis Pichette, Francois St-Maurice, Patrick Teefy, Samer Mansour, Saleem Kassam, Stephen Cheung, Anthony D Siega, Dennis O'Keefe, Eric Sabbah, Alan Bell, Guy Chouinard, Brian Wong, Mark Miller, Daniel Gaudet, Pierre Lachance, Iqbal Bata, Robert Petrella, Denis Gossard, Richard Dumas, Douglas Ing, Hagop Boyrazian, Ricardo Bessoudo, Thao T Huynh, Randy Hart, Jasmin Belle-Isle, Dinkar Shukla, Allan Kelly, Giuseppe Mazza, James Cha, Sam Henein, Andre Frechette, Saul Vizel, Joanne F Liutkus, Michael O'Mahony, Frank Halperin, Jacobus Kooy, John Graham, Allan Bailey, Ronald Wojcik, Igor Wilderman, Tibor Turi, Ákos Motyovszki, Béla Merkely, Csaba Király, Péter Andrássy, Zsolt Sárszegi, Tibor Fülöp, Zsolt Zilahi, István Édes, Andras Papp, Gábor Müller, Anna Czigány, Szilárd Zólyomi, László Korányi, János Takács, Ferenc Juhász, Bela Benczur, Sándor Kancz, András Földi, András C Nagy, Judit Bakai, István Greschik, László Püski, László Nagy, Róbert Kirschner, Roman Kuchar, Petr Hajek, Ladislav Busak, Daniel Michalik, Ivo Matyasek, Ivana Marusincova, Dusan Kucera, Ondrej Jerabek, Michaela Honkova, Vratislav Dedek, Ivan Rihacek, Pavel Kos, Josef Slaby, Martina Machkova, Eva Zidkova, Lubomir Elbl, Hana Grunfeldova, Jiri Carda, Vladimir Mrozek, Jiri Maly, Richard Milkovic, Jan Malecha, Hana Skalicka, Ivo Oral, Eva Krcova, Libor Lisa, Jan Belohlavek, Roman Miklik, Ondrej Cermak, Jana Bednarova, Zdenek Peroutka, Jindrich Spinar, Andreas Wilke, Karl-Friedrich Appel, Jens Taggeselle, Andreas Förster, Nicole Toursarkissian, Ekkehard Schmidt, Jochen Bott, Ayham Al-Zoebi, Dirk Hennig, Sabine Fischer, Norbert Schön, Joachim Sauter, Gregor Simonis, Ruth Nischik, Werner Rieker, Isabelle Schenkenberger, Thomas Behnke, Gerhard Klausmann, Michael Jeserich, Dietmar Trenk, Ingo Weigmann, Hannes Reuter, Reinhard Rummel, Candy von Münchhausen, Charlotte von Engelhardt, Eishun Horibe, Taro Shibasaki, Tomohiko Sato, Tsunekazu Kakuta, Ichiro Michishita, Michinao Tan, Ryoji Ishiki, Takahiko Aoyama, Shinichi Higashiue, Yawara Niijima, Akira Idogaki, Toru Hasegawa, Arihiro Kiyosue, Yoshiaki Tomobuchi, Katsunori Kawamitsu, Satsuki Kawasaki, Yoshiki Hata, Kazuki Fukui, Kozaburo Seki, Takashi Takenaka, Mitsuru Abe, Noriaki Utsu, Atsuyuki Oono, Kazuhisa Mitsuo, Atsushi Sueyoshi, Atsushi Hirohata, Mitsuru Tsujimoto, Osamu Ueda, Shinichi Takase, Masahiro Suzuki, Satoru Sakuragi, Fumi Yamamoto, Noritaka Fujimoto, Shigeo Kakinoki, Tatsushi Sugiura, Hiroshi Sugino, Toshihiro Nakamura, Toshiaki Kadokami, Hiroki Uehara, Masahiro Ono, Koichi Yokoya, Akihiro Koike, Sei Komatsu, Masahiro Sonoda, Hideki Ueno, Tomofumi Doi, Yuichiro Takagi, Kazuteru Fujimoto, Yutaka Eki, Munenori Okubo, Kenichiro Sasaki, Martijn van Eck, Eelko Ronner, Salem The, Ruud van de Wal, Pieter Nierop, Cornelis de Nooijer, Henri Werner, Iris Westendorp, Coen van der Zwaan, Hendrikus Crijns, Jan H Cornel, Sipke Strikwerda, Robert Bos, Edwin de Melker, Adrianus Kuijper, Hans Louwerenburg, Jacobus Plomp, Jan-Melle Dantzig, Francisco Prins, Henricus van Kesteren, Frank Willems, Giovanni Amoroso, Gabriela Carnero, Ernesto Duronto, Diego Besada, Carolina Chacon, Pedro Zangroniz, Silvana Solis, Alberto Liberman, Virginia Sernia, Andres Alvarisqueta, Laura Maffei, Oscar G Vilamajo, Celso García, Maximiliano Sicer, Juan Muntaner, Anselmo Bordonava, Juan Albisu, Alejandra Zanini, Lucas Rista, Miguel Hominal, José N Estrada, Aldo Prado, Diego M Gosparini, Beatriz Schiavi, Armando G Castillo, José G Ruíz, Guillermo R Martinez, Víctor G López, Enrique L Rosas, Gabriel R Lopez, Elias G Cantu, Manuel de los Ríos Ibarra, Francisco P Padilla, Jose P Carrasco, Luis V Carrillo, Joel D García, Alfredo N Askar, Carlos A Salinas, Marco A Gamba, Carlos G Sanchez, Arnulfo G Cantú, Raul V Sánchez, Jaime C Madrigal, Rafael H Urbano, Andrés Í Romo, José R González Juanatey, Paolo Racugno, Angel C Fillat, José M de la Torre Hernández, Juan A Peláez, Jorge B Cortada, Pablo G Pavia, Manuel J Navarro, Roberto M Asenjo, Francisco F Díaz, Eduard B Peligero, Fernando A Manterola, Antonio F Ortiz, Juan D Mediavilla García, Francisco M Ortuño, Tomás R Vera, Alfonso S González, Jaime A Viñas, Francisco J Fernández Portales, Petra S Mayordomo, Francisco B Ojeda, Antonio R Domínguez, Rosa S González, Diego B Guerrero, Juan M Ruiz Nodar, Xavier G Marimon, José G Margáez, Roberto M Aguilera, José F Díaz Fernández, José L Zamorano Gómez, Vicente B González, Bruno G del Blanco, Ignacio P Pérez, Mercé R Moreno, Ainhoa R Ereño, José A García Lledó, Juan Prieto, Alex Villablanca, Carlos Raffo, Christian Pincetti, Carlos Conejeros, Oscar Roman, Manuel Rodriguez, Paola Varleta, Cindy Goldberg, Jorge Sandoval, German Arriagada, Lucio Leon, Sergio Potthoff, Jorge Cobos, Christian Figueroa, Ellen Makotoko, Nyda Fourie, Lesley Burgess, Hendrik Nortje, Rust Theron, Perumal Pillai, Naresh Ranjith, Julien Trokis, Soobramoney Pillay, Jeevren Reddy, Theema Nunkoo, Cornelia Kapp, Dorothea Urbach, Lawrence Distiller, Adrian Horak, Louis van Zyl, Kathleen Coetzee, Zelda Punt, Junaid Bayat, 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Karol Micko, Juraj Palka Jr, Vladimir Sivak, Dalby Kristensen, Jens Refsgaard, Lene Holmvang, Ulrik Dixen, Henrik Nielsen, Kenneth Egstrup, Lisette O Jensen, Roman Sykulski, Ole Rasmussen, Alin Andries, Anders Luckow, Gitte Nielsen, Torben Sørensen, Chaiyasith Wongvipaporn, Noppadol Chamnarnphol, Suphot Srimahachota, Nakarin Sansanayudh, Srun Kuanprasert, Damras Tresukosol, Bancha Sookananchai, Mehmet Kanadasi, Turkay Ozcan, Murathan Kucuk, Zeki Ongen, Ertugrul Okuyan, Alev Arat, Sadik Acikel, Ahmet Yalcin, Umit Guray, Ceyhun Ceyhan, Necla Ozer, Sakir Arslan, Oskar Angerås, Nina Johnston, Ann-Charlotte Weiderman, Stellan Bandh, Ole Hansen, Hans Larnefeldt, Dawid Kusiak, Carl-Johan Lindholm, Anders Hedman, David Erlinge, Dan Curiac, Pia Lundman, Roberto Zucconi-Mazzini, Layth Aladellie, Jens Jensen, Jan Verwerft, Mathias Vrolix, Dirk Faes, Harry Striekwold, Peter Sinnaeve, Patrick Timmermans, Antoine Guedes, Marc Delforge, Jan Nimmegeers, Francis Stammen, Ian Buysschaert, Etienne Hoffer, Geert Hollanders, Geert Vervoort, Patrick Coussement, Stefan de Maeseneire, Luc Janssens, Stein A Gravdal, Knut Risberg, Lars Gullestad, Ola D Hofseth, Dennis Nilsen, Knut T Lappegård, Christian van den Heuvel, Charlotte Gibbs, Alamdar Khusrawi, Satish Arora, Tadeusz Tomala, Thorbjørn Kjærnli, Jan Berg-Johansen, Robert Hagemeier, Gunnar Skjelvan, David Colquhoun, John Amerena, Claire Morbey, Christopher Hammett, Anthony Dart, Ronald Lehman, Andrew Hamilton, Matthew Worthley, Peter Purnell, Alan Whelan, Richard MacIsaac, Ktut Arya, Sultan Linjawi, Joseph Proietto, Lakshman Prasad, Aldo Rodriguez, Armando Godoy, Victor Rodriguez, Percy Berrospi, Carlos Chavez, Sandra Negron, Javier Heredia, Felix Medina, Helard Manrique, Walter Cabrera, Fernando Cordova, Trinidad Quinteros, Jaime M Haro, Susana Regalado, Javier Guitton, Hugo Arbanil, Michel Pansieri, Eric Decoulx, Pascal Goube, Axel de Labriolle, Jean N Labeque, Gregoire Range, Yves Cottin, Gilles Montalescot, Guillaume Cayla, Nicolas Danchin, Denis Angoulvant, Emile Ferrario, Meyer Elbaz, Olivier Dubreuil, Philippe G Steg, Caroline Fontaine, Emmanuel Sorbets, Hafiz Omer, Shukri Al-Saif, Hussam Al-Faleh, Abdullah Al-Shehri, Halia Alshehri, Rasha Bazari, Pak Hei, Man Ying, Michael Chan, Michelle Wong, Ronald Ma, Shing C Siu, Chiu C Tsang, Maurizio Ferrario, Emilio Assanelli, Michele Senni, Piermarco Piatti, Paolo Calabrò, Stefano Urbinati, Massimo Michisanti, Ferdinando Varbella, Salvatore de Cosmo, Roberto Trevisan, Sandro Bellotti, Giuseppe Di Pasquale, Angelo S Bongo, Massimo Uguccioni, Edoardo Mannucci, Ciro Mauro, Mauro Ragonese, Claudio Fresco, Maurizio Turturo, Rossella Marcucci, Manuel J Lievano Triana, Camilo Arana, Jose Accini, Rodrigo Botero, Marlena Muzyk-Osikowicz, Fredy T Dada, Gregorio S Vallejo, Fernando Manzur, Daniel Isaza, Dora Molina, Juan G Mesa, Alvaro Quintero, Kai Nyman, Jyrki Mäkelä, Jorma Strand, Sakari Nieminen, Jyrki Taurio, Matti Kuusela, Timo Valle, Mikko Pietilä, Sakari Kekki, Timo Strandberg, Marc Klutstein, Gabriel Greenberg, Yoseph Rozenman, Ehud Chorin, Ariel Roguin, Basil Lewis, Amir Bashkin, Edgar Tan, Jose P Prado, Arthur Ferrolino, Noe Babilonia, Benny Barbas, Generoso Matiga, Raul M Coching, Heinz Drexel, Helmut Brath, Christoph Schnack, Ursula Hanusch, Evelyn Fließer-Görzer, Bernhard Paulweber, Christoph Ebenbichler, Rudolf Prager, Kurt Huber, Michael Wolzt, Johann Auer, Rudolf Berger, Gerit-Holger Schernthaner, Gabriela Stanciulescu, Mihai Creteanu, Marilena Spiridon, Viorica Dobreanu, Dragos Vinereanu, Laura C Iosipescu, Octavian Istratoaie, Ioan Coman, Constantin Militaru, Mircea Cinteza, Peter R Sinnaeve, José C Nicolau, José F Kerr Saraiva, Ramón Corbalán, Petr Widimský, Steen D Kristensen, Juha Hartikainen, Harald Darius, Hung F Tse, Robert G Kiss, Prem Pais, Eli Lev, Leonardo de Luca, Gabriel A Ramos López, Frederic Kontny, Noe A Babilonia, Dmitry A Zateyshchikov, Mikhail Ruda, Omer Elamin, František Kovář, Anthony J Dalby, Héctor Bueno, Chern-En Chiang, Alexander Parkhomenko, Tuan Q Nguyen, Maria Leonsson-Zachrisson, Herrada, Anthony, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Royal Brompton Hospital, McMaster University [Hamilton, Ontario], Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], St. Michael's Hospital, University of Toronto, Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Uppsala University Hospital, Uppsala Universitet [Uppsala], AstraZeneca, Tokai University, Uppsala University, Imperial College London, Saint Luke's Mid America Heart Institute, University of Missouri [Kansas City] (UMKC), University of Missouri System, University of New South Wales [Sydney] (UNSW), University of Texas Southwestern Medical Center [Dallas], Stanford University, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Bhatt, D, Steg, P, Mehta, S, Leiter, L, Simon, T, Fox, K, Held, C, Andersson, M, Himmelmann, A, Ridderstrale, W, Chen, J, Song, Y, Diaz, R, Goto, S, James, S, Ray, K, Parkhomenko, A, Kosiborod, M, Mcguire, D, Harrington, R, Santos, V, Jain, A, Lendel, I, Russo, M, Haught, W, Bouza, M, Gogia, H, Banerjee, S, Kichura, G, Kantaros, L, Padron, F, Passi, R, Stone, J, Pursley, M, D'Urso, M, Gardner, T, Bennett, J, Nour, K, Saini, S, Zhang, W, Kumbhani, D, Thomas, D, Angiolillo, D, Bertolet, B, Roman-Miranda, A, Black, R, Manshadi, R, Vaca, C, Blanco, A, Napoli, M, Brabham, D, Akyea-Djamson, A, Desai, P, Prasada, S, Khaira, A, Forgosh, L, Lieber, I, Umpierrez, G, Singal, D, Londono, J, Fraser, N, Ruiz, J, Vega, D, Rodriguez, L, Brown, C, Syed, F, Aggarwala, G, Eaves, W, Foster, M, Gupta, D, Avino, D, Asfour, W, Tonnessen, G, Zhao, X, Singh, N, Brockmyre, A, Lepor, N, Shammas, N, Blick, D, Hearne, S, Prodafikas, J, Carell, E, Izzo, M, Karim, A, Zakhary, B, Atieh, M, Leichter, S, Meadows, C, Hotchkiss, D, Abu-Fadel, M, Wiseman, A, Bander, J, Shah, M, Ganim, R, Sopko, K, Khan, M, Lloret, R, Weirick, T, Mehta, R, Thadani, U, Bhargava, A, Moya, J, Staniloae, C, Guerra, Y, Chhabra, A, Kosmicki, D, Shaheen, W, Mohammed, A, Bitters, J, Pattanayak, J, Javier, J, Srivastava, S, Phillips, R, Al-Amin, J, Lillestol, M, Simpson, P, Hazan, L, Amin, A, Shah, G, Korpas, D, Platt, B, Dickert, J, Puente, O, Hiotis, L, Doyle, T, Rajan, R, Meholick, A, Gring, C, Hage-Korban, E, Feldman, R, Colfer, H, Butman, S, Hart, T, Huling, R, Eshaghian, S, Quintana, O, Cheung, D, Handel, F, Rodriguez, M, Suh, D, Gordon, P, Pressman, G, Bauer, M, French, W, Barettella, M, Chatrathi, S, Suresh, D, Goldberg, R, Huth, M, Younis, L, Rahman, A, Mascolo, R, Welch, M, Suneja, R, Smith, S, Shurmur, S, Agaiby, J, Jingo, A, Johnston, J, Beth, M, Vlastaris, A, Kemp, S, Taheri, H, Pereira, E, Deyoung, M, Hawa, Z, Smith, R, Galski, T, Garas, S, Reddy, M, Sharma, S, Hargrove, J, Treasure, C, Emerson, R, Haddad, T, Rohr, K, Levinson, L, Gaona, R, Uretsky, B, Maheshwari, H, Lee, D, Kinnaman, S, Singal, R, Geohas, J, Gigliotti, O, Raisinghani, A, Khurana, C, Hella, B, Kelberman, M, Voyce, S, Singh, S, Lo, E, Singh, P, Goodfellow, R, Fischer, S, Lorraine, R, Turner, T, Shanes, J, Busch, R, Broker, R, Zaniewski, M, Pounds, K, Debs-Perez, G, Ong, S, Frandsen, B, Fullington, D, Jaffrani, N, Khan, A, Lee, M, Pouzar, J, Revtyak, G, Gonzalez, J, Nakhle, S, Murillo, A, Young, D, Makam, S, Syed, M, Woolf, K, Grena, P, Alfata, S, Mahal, S, Hoffman, D, Kizhakekuttu, T, Deering, J, Bhavsar, J, Mikesell, S, Wilson, W, Wilson, V, El, S, Spinale, F, Kannarkat, V, Rao, S, Hanson, L, Bertsch, J, Gonzalez-Ortiz, E, Severino, N, Willis, J, Schock, J, Bakhtari, L, Gazmuri, R, Ansari, S, Hall, J, Mehta, A, Shealy, N, Zarich, S, Singh, D, Vora, K, Andrawis, N, Molter, D, Maron, D, Cardona, J, D'Agostino, R, Arshad, T, Samaan, R, Jones, D, Presser, D, Heath, J, Green, S, Bittar, G, Henry, S, Korn, D, Schmedtje, J, Nadar, V, Graham, B, Labroo, A, Clavijo, L, Roseman, H, Ledesma, G, Rosen, R, Dor, I, Kirby, W, Sutton, J, Eder, F, Iteld, B, Gomez-Cortes, J, Buchbinder, M, Kasper, J, Terrelonge, A, Torres, G, Jagielo, T, Alvarez, J, Handelsman, Y, Guillen, M, Richwine, R, Lewy-Alterbaum, L, Corder, C, Arvind, M, Bolshoun, D, Mikhail, M, Minton, S, Alvarado, O, Abbott, J, Cauthen, B, Welter, R, Mintz, R, Cox, J, Quick, A, Weiss, M, Dy, J, Zebrack, J, Gandelman, G, Hegde, V, Silver, M, Degregorio, M, Lawson, W, Paa, C, Bortnick, A, Krolick, M, Sotolongo, R, Cheirif, J, Kumar, P, Jetty, P, Patel, A, Kruk, M, Kobielusz-Gembala, I, Rewerska, B, Madrzejewski, A, Milewski, K, Cygler, J, Petryka-Mazurkiewicz, J, Jastrzebski, W, Korecki, J, Fil, W, Prokopczuk, J, Bochenek, A, Wujkowski, M, Witek, R, Konczakowski, P, Miekus, P, Szczasny, M, Musial, W, Cymerman, K, Lampart, J, Mikosinski, J, Szynal, S, Fares, I, Opolski, G, Mazur, S, Wozakowska-Kaplon, B, Bijata-Bronisz, R, Wierucki, L, Losa, B, Drelich, G, Konieczny, M, Starczewski, P, Pawlowicz, L, Jesionowski, P, Jurowiecki, J, Gniot, J, Czyzycki, M, Stania, K, Kucharczyk-Bauman, I, Busz-Papiez, B, Karczmarczyk, A, Sudnik, W, Koszek, A, Kolodziej, P, Skwarna, B, Jaramillo, N, Jankowski, M, Czochra, W, Kinasz, L, Miklaszewicz, B, Stasinska, T, Pluta, W, Basiak, M, Rusicka, T, Niedbal-Yahfouf, I, Popenda, G, Korzeniak, R, Mirek, A, Mariankowski, R, Wojnowski, L, Korol, M, Baszak, J, Podolec, P, Piesiewicz, W, Zurakowski, A, Luengas, C, Skura, M, Pilecki, P, Majchrzak, P, Krzyzagorska, E, Drozd, M, Kaczmarek, B, Sliwinska, T, Zelazowska, K, Sztembis, R, Landa, K, Matyszczak-Toniak, L, Strojek, K, Piepiorka, M, Malinowski, R, Gorska, M, Stolarczyk-Sowa, E, Romanowski, L, Zinka, E, Reszka, Z, Skierkowska, J, Uzunow, A, Laskowska-Derlaga, E, Puntus, E, Kosmacheva, E, Koziolova, N, Pavlov, P, Supryadkina, T, Didenko, Y, Kopylov, P, Kazakov, A, Aksentiev, S, Vishneva, E, Repin, A, Smolenskaya, O, Mantserova, O, Khrustalev, O, Privalova, E, Konstantinov, V, Boldueva, S, Ezhov, A, Chernyavsky, A, Kamalov, G, Galyavich, A, Zubeeva, G, Nechaeva, G, Shustov, S, Dzhaiani, N, Treshkur, T, Osokina, N, Panov, A, Shutemova, E, Makukhin, V, Kropotina, T, Tsyba, L, Karpov, Y, Sizova, J, Ballyuzek, M, Tarasov, N, Demchenko, E, Barbarash, O, Moiseev, V, Markov, V, Kuznetsov, V, Viktorova, I, Sergienko, I, Ermoshkina, L, Khasanov, N, Khlevchuk, T, Baglikov, A, Shalaev, S, Zonova, E, Reznik, E, Haisheva, L, Morugova, T, Lomakin, N, Vishnevsky, A, Shvarts, Y, Magnitskaya, O, Mikhailusova, M, Pavlysh, E, Libov, I, Zateyschikova, A, Kostenko, V, Edin, A, Khovaeva, Y, Zakharov, K, Stryuk, R, Khirmanov, V, Kanorskiy, S, Yakushin, S, Barabashkina, A, Li, H, Zhao, Q, Zhang, J, Ma, J, He, Y, Luo, M, Zhang, A, Zhang, N, Chai, Y, Ma, G, Wang, H, Liu, Z, He, L, Song, Z, Dong, X, Tao, L, Li, Z, Su, X, Kong, X, Niu, H, Ge, J, Luo, Z, Huang, W, Peng, D, Yuan, Z, Milanova, M, Tenev, D, Gogov, A, Karageorgiev, D, Kolchev, T, Rusev, N, Georgieva, N, Kondov, R, Rusinov, V, Petrov, I, Stanchev, G, Konteva, M, Dincheva, A, Yaneva, Z, Vatova, R, Ilieva, K, Runev, N, Kolomanov, B, Iliev, N, Tisheva, S, Chompalova, B, Tokmakova, M, Raev, D, Byanov, K, Markov, D, Mihov, L, Mihov, A, Milcheva, N, Minchev, M, Mollov, M, Borisov, B, Tihchev, T, Karakolev, V, Dimov, B, Georgiev, S, Smilov, L, Koo, B, Ahn, T, Hong, S, Yoon, J, Oh, S, Jeong, M, Kim, D, Chang, K, Kim, W, Hahn, J, Cha, K, Lee, J, Choi, S, Nam, C, Chae, I, Park, Y, Tahk, S, Shin, W, Chae, J, Kim, B, Bae, J, Park, W, Rha, S, Choi, Y, Hwang, J, Park, H, Baracioli, L, Guimaraes, F, Vasconcellos, E, Saraiva, J, Pereira, A, Santos, Q, Rossi, P, Maia, L, Madeira, M, Pereira, M, Botelho, R, Reis, G, Eliaschewitz, F, Borges, J, Nascimento, C, Fortes, J, de Souza, W, Pimentel, P, Hissa, M, Franchetti, M, Precoma, D, Ortiz, C, Hernandes, M, Saporito, W, dos Santos, F, Kormann, A, Neuenschwander, F, Dutra, O, Rassi, N, Tanajura, L, Souza, J, Junior, D, Leaes, P, Forte, A, Bonansea, T, Marin, J, Machado, B, Cerqueira, M, Silva, F, Michalaros, Y, Manenti, E, Cercato, C, Figueiredo, E, Liu, M, Wang, Y, Lee, T, Fang, C, Wu, Y, Ueng, K, Sheu, H, Lai, W, Hsieh, I, Chen, Z, Chiang, C, Shyu, K, Hsia, C, Mar, G, Chan, S, Wu, C, Tseng, W, Yeh, H, Wang, J, Hou, C, Sorokina, I, Dolzhenko, M, Horoshko, O, Karpenko, O, Rudenko, L, Vakaliuk, I, Kulyk, A, Levchenko, O, Prokhorov, O, Reshotko, D, Sorokivskyy, M, Velichko, N, Maslovskyi, V, Teliatnikova, Z, Dotsenko, S, Krakhmalova, O, Kraiz, I, Zharinova, V, Bula, L, Kaydashev, I, Molodtsov, V, Rasputina, L, Pidlisna, V, Lysunets, O, Kravchenko, A, Glushko, L, Khomazyuk, T, Svyshchenko, Y, Parkhomenko, O, Mankovsky, B, Abrahamovych, O, Yagensky, A, Stanislavchuk, M, Vasilyeva, L, Sokolova, L, Sychov, O, Tseluyko, V, Kyrychenko, I, Rishko, M, Furkalo, S, Gallo, R, Bertrand, O, Constance, C, Sussex, B, Zadra, R, Kouz, S, Chehayeb, R, Pandey, A, Dion, D, Bailey, G, Hill, L, Ramanathan, K, Dorsch, M, Nanji, A, Babapulle, M, Montigny, M, Gosselin, G, Dehghani, P, Rupka, D, Le May, M, Pichette, F, St-Maurice, F, Teefy, P, Mansour, S, Kassam, S, Cheung, S, Siega, A, O'Keefe, D, Sabbah, E, Bell, A, Chouinard, G, Wong, B, Miller, M, Gaudet, D, Lachance, P, Bata, I, Petrella, R, Gossard, D, Dumas, R, Ing, D, Boyrazian, H, Bessoudo, R, Huynh, T, Hart, R, Belle-Isle, J, Shukla, D, Kelly, A, Mazza, G, Cha, J, Henein, S, Frechette, A, Vizel, S, Liutkus, J, O'Mahony, M, Halperin, F, Kooy, J, Graham, J, Bailey, A, Wojcik, R, Wilderman, I, Turi, T, Motyovszki, A, Merkely, B, Kiss, R, Kiraly, C, Andrassy, P, Sarszegi, Z, Fulop, T, Zilahi, Z, Edes, I, Papp, A, Muller, G, Czigany, A, Zolyomi, S, Koranyi, L, Takacs, J, Juhasz, F, Benczur, B, Kancz, S, Foldi, A, Nagy, A, Bakai, J, Greschik, I, Puski, L, Nagy, L, Kirschner, R, Kuchar, R, Hajek, P, Busak, L, Michalik, D, Matyasek, I, Marusincova, I, Kucera, D, Jerabek, O, Honkova, M, Dedek, V, Rihacek, I, Kos, P, Slaby, J, Machkova, M, Zidkova, E, Elbl, L, Grunfeldova, H, Carda, J, Mrozek, V, Maly, J, Milkovic, R, Malecha, J, Skalicka, H, Oral, I, Krcova, E, Lisa, L, Belohlavek, J, Miklik, R, Cermak, O, Bednarova, J, Peroutka, Z, Spinar, J, Wilke, A, Appel, K, Taggeselle, J, Forster, A, Toursarkissian, N, Schmidt, E, Bott, J, Al-Zoebi, A, Hennig, D, Schon, N, Sauter, J, Simonis, G, Nischik, R, Rieker, W, Schenkenberger, I, Behnke, T, Klausmann, G, Jeserich, M, Trenk, D, Weigmann, I, Reuter, H, Rummel, R, von Munchhausen, C, von Engelhardt, C, Horibe, E, Shibasaki, T, Sato, T, Kakuta, T, Michishita, I, Tan, M, Ishiki, R, Aoyama, T, Higashiue, S, Niijima, Y, Idogaki, A, Hasegawa, T, Kiyosue, A, Tomobuchi, Y, Kawamitsu, K, Kawasaki, S, Hata, Y, Fukui, K, Seki, K, Takenaka, T, Abe, M, Utsu, N, Oono, A, Mitsuo, K, Sueyoshi, A, Hirohata, A, Tsujimoto, M, Ueda, O, Takase, S, Suzuki, M, Sakuragi, S, Yamamoto, F, Fujimoto, N, Kakinoki, S, Sugiura, T, Sugino, H, Nakamura, T, Kadokami, T, Uehara, H, Ono, M, Yokoya, K, Koike, A, Komatsu, S, Sonoda, M, Ueno, H, Doi, T, Takagi, Y, Fujimoto, K, Eki, Y, Okubo, M, Sasaki, K, van Eck, M, Ronner, E, The, S, van de Wal, R, Nierop, P, de Nooijer, C, Werner, H, Westendorp, I, van der Zwaan, C, Crijns, H, Cornel, J, Strikwerda, S, Bos, R, de Melker, E, Kuijper, A, Louwerenburg, H, Plomp, J, Dantzig, J, Prins, F, van Kesteren, H, Willems, F, Amoroso, G, Carnero, G, Duronto, E, Besada, D, Chacon, C, Zangroniz, P, Solis, S, Liberman, A, Sernia, V, Alvarisqueta, A, Maffei, L, Vilamajo, O, Garcia, C, Sicer, M, Muntaner, J, Bordonava, A, Albisu, J, Zanini, A, Rista, L, Hominal, M, Estrada, J, Prado, A, Gosparini, D, Schiavi, B, Castillo, A, Martinez, G, Lopez, V, Rosas, E, Lopez, G, Cantu, E, de los Rios Ibarra, M, Padilla, F, Carrasco, J, Carrillo, L, Garcia, J, Askar, A, Salinas, C, Gamba, M, Sanchez, C, Cantu, A, Sanchez, R, Madrigal, J, Urbano, R, Romo, A, Gonzalez Juanatey, J, Racugno, P, Fillat, A, de la Torre Hernandez, J, Pelaez, J, Cortada, J, Pavia, P, Navarro, M, Asenjo, R, Diaz, F, Peligero, E, Manterola, F, Ortiz, A, Mediavilla Garcia, J, Ortuno, F, Vera, T, Gonzalez, A, Vinas, J, Fernandez Portales, F, Mayordomo, P, Ojeda, F, Dominguez, A, Gonzalez, R, Guerrero, D, Ruiz Nodar, J, Marimon, X, Margaez, J, Aguilera, R, Diaz Fernandez, J, Zamorano Gomez, J, Gonzalez, V, del Blanco, B, Perez, I, Moreno, M, Ereno, A, Garcia Lledo, J, Prieto, J, Villablanca, A, Raffo, C, Pincetti, C, Conejeros, C, Roman, O, Varleta, P, Goldberg, C, Sandoval, J, Arriagada, G, Corbalan, R, Leon, L, Potthoff, S, Cobos, J, Figueroa, C, Makotoko, E, Fourie, N, Burgess, L, Nortje, H, Theron, R, Pillai, P, Ranjith, N, Trokis, J, Pillay, S, Reddy, J, Nunkoo, T, Kapp, C, Urbach, D, Distiller, L, Horak, A, van Zyl, L, Coetzee, K, Punt, Z, Bayat, J, Dawood, S, Mitha, I, Padayachee, T, Hoosen, F, Dalby, A, Prabhavathi, Gowdaiah, P, Mehta, V, Chag, M, Gadkari, M, Ramamurthee, K, Das, A, Sawhney, J, Sathe, P, Adhyapak, S, Nguyen, T, Pham, V, Do, H, Nguyen, A, Nguyen, H, Truong, B, Jamil-Copley, S, Lang, C, Pell, A, Zaman, A, Storey, R, Swanson, N, Sharman, D, Braganza, D, Hammond, P, Moriarty, A, Bain, S, Pye, M, Sharp, A, Blagden, M, Randeva, H, Myhill, T, Viswanathan, G, Keeling, P, Clifford, P, Saxena, M, Lyons, K, Mcmurray, J, Jaafar, F, Murphy, C, Cartwright, S, Abouglila, K, Antalik, L, Krajci, P, Urban, M, Fazekas, F, Pella, D, Koleny, D, Vykoukalova, T, Macek, V, Vinanska, D, Jamriskova, L, Such, S, Fulop, P, Farsky, S, Bugan, V, Strbova, J, Micko, K, Palka Jr, J, Sivak, V, Kristensen, D, Refsgaard, J, Holmvang, L, Dixen, U, Nielsen, H, Egstrup, K, Jensen, L, Sykulski, R, Rasmussen, O, Andries, A, Luckow, A, Nielsen, G, Sorensen, T, Wongvipaporn, C, Chamnarnphol, N, Srimahachota, S, Sansanayudh, N, Kuanprasert, S, Tresukosol, D, Sookananchai, B, Kanadasi, M, Ozcan, T, Kucuk, M, Ongen, Z, Okuyan, E, Arat, A, Acikel, S, Yalcin, A, Guray, U, Ceyhan, C, Ozer, N, Arslan, S, Angeras, O, Johnston, N, Weiderman, A, Bandh, S, Hansen, O, Larnefeldt, H, Kusiak, D, Lindholm, C, Hedman, A, Erlinge, D, Curiac, D, Lundman, P, Zucconi-Mazzini, R, Aladellie, L, Jensen, J, Verwerft, J, Vrolix, M, Faes, D, Striekwold, H, Sinnaeve, P, Timmermans, P, Guedes, A, Delforge, M, Nimmegeers, J, Stammen, F, Buysschaert, I, Hoffer, E, Hollanders, G, Vervoort, G, Coussement, P, de Maeseneire, S, Janssens, L, Gravdal, S, Risberg, K, Gullestad, L, Hofseth, O, Nilsen, D, Lappegard, K, van den Heuvel, C, Gibbs, C, Khusrawi, A, Arora, S, Tomala, T, Kjaernli, T, Berg-Johansen, J, Hagemeier, R, Skjelvan, G, Colquhoun, D, Amerena, J, Morbey, C, Hammett, C, Dart, A, Lehman, R, Hamilton, A, Worthley, M, Purnell, P, Whelan, A, Macisaac, R, Arya, K, Linjawi, S, Proietto, J, Prasad, L, Rodriguez, A, Godoy, A, Rodriguez, V, Berrospi, P, Chavez, C, Negron, S, Heredia, J, Medina, F, Manrique, H, Cabrera, W, Cordova, F, Quinteros, T, Haro, J, Regalado, S, Guitton, J, Arbanil, H, Pansieri, M, Decoulx, E, Goube, P, de Labriolle, A, Labeque, J, Range, G, Cottin, Y, Montalescot, G, Cayla, G, Danchin, N, Angoulvant, D, Ferrario, E, Elbaz, M, Dubreuil, O, Fontaine, C, Sorbets, E, Omer, H, Al-Saif, S, Al-Faleh, H, Al-Shehri, A, El-Amin, O, Alshehri, H, Bazari, R, Hei, P, Ying, M, Chan, M, Wong, M, Ma, R, Siu, S, Tsang, C, Ferrario, M, Assanelli, E, Senni, M, Piatti, P, Calabro, P, Urbinati, S, Michisanti, M, Varbella, F, de Cosmo, S, Trevisan, R, Bellotti, S, Di Pasquale, G, Bongo, A, Uguccioni, M, Mannucci, E, Mauro, C, Ragonese, M, Fresco, C, Turturo, M, Marcucci, R, Lievano Triana, M, Arana, C, Accini, J, Botero, R, Muzyk-Osikowicz, M, Dada, F, Vallejo, G, Manzur, F, Isaza, D, Molina, D, Mesa, J, Quintero, A, Nyman, K, Makela, J, Strand, J, Nieminen, S, Taurio, J, Kuusela, M, Valle, T, Pietila, M, Kekki, S, Strandberg, T, Klutstein, M, Greenberg, G, Rozenman, Y, Chorin, E, Roguin, A, Lewis, B, Bashkin, A, Tan, E, Prado, J, Ferrolino, A, Babilonia, N, Barbas, B, Matiga, G, Coching, R, Drexel, H, Brath, H, Schnack, C, Hanusch, U, Fliesser-Gorzer, E, Paulweber, B, Ebenbichler, C, Prager, R, Huber, K, Wolzt, M, Auer, J, Berger, R, Schernthaner, G, Stanciulescu, G, Creteanu, M, Spiridon, M, Dobreanu, V, Vinereanu, D, Iosipescu, L, Istratoaie, O, Coman, I, Militaru, C, Cinteza, M, Nicolau, J, Kerr Saraiva, J, Widimsky, P, Kristensen, S, Hartikainen, J, Darius, H, Tse, H, Pais, P, Lev, E, de Luca, L, Ramos Lopez, G, Kontny, F, Zateyshchikov, D, Ruda, M, Elamin, O, Kovar, F, Bueno, H, Leonsson-Zachrisson, M, Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Royal Brompton and Harefield NHS Foundation Trust-Imperial College London
Subjects: Male, Platelet Aggregation Inhibitors/therapeutic use, THEMIS Steering Committee and Investigators, medicine.medical_treatment, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 030204 cardiovascular system & hematology, Coronary Angiography, Stroke/epidemiology, Coronary artery disease, DOUBLE-BLIND, 0302 clinical medicine, Hemorrhage/chemically induced, acetylsalicylic acid, antidiabetic agent, placebo, ticagrelor, Secondary Prevention, Medicine, 030212 general & internal medicine, Myocardial infarction, Coronary Artery Bypass, Cardiovascular Diseases/mortality, 11 Medical and Health Sciences, OUTCOMES, Aspirin, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, General Medicine, Middle Aged, Clopidogrel, 3. Good health, Ticagrelor/therapeutic use, DRUG-ELUTING STENTS, CLOPIDOGREL, Cardiology, PLATELET INHIBITION, Drug Therapy, Combination, Female, Life Sciences & Biomedicine, Ticagrelor, TIMI, medicine.drug, Coronary Artery Disease/complications, medicine.medical_specialty, Hypoglycemic Agents/therapeutic use, POOLED ANALYSIS, 03 medical and health sciences, Medicine, General & Internal, Percutaneous Coronary Intervention, Double-Blind Method, General & Internal Medicine, Internal medicine, Myocardial Infarction/epidemiology, Humans, Aged, Science & Technology, ANTIPLATELET THERAPY, business.industry, Diabetes Mellitus, Type 2/complications, ELEVATION MYOCARDIAL-INFARCTION, RIVAROXABAN, Percutaneous coronary intervention, medicine.disease, ASPIRIN, Coronary Stenosis/diagnostic imaging, Aspirin/therapeutic use, Conventional PCI, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 215333.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, pinteraction=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p
Published: 2019

42. Corrigendum

Author: Kou-Gi Shyu
Subjects: Clinical Biochemistry, General Medicine, Biochemistry
Published: 2018

43. Prognostic impact of renal dysfunction in patients with acute coronary syndrome-role beyond the CHA2DS2-VASc score: Data from Taiwan acute coronary syndrome full spectrum registry

Author: Su Kiat Chua, Huey Ming Lo, Chiung Zuan Chiu, and Kou Gi Shyu
Subjects: medicine.medical_specialty, Acute coronary syndrome, Pediatrics, Receiver operating characteristic, business.industry, Renal function, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, Comorbidity, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Internal medicine, CHA2DS2–VASc score, medicine, Cardiology, 030212 general & internal medicine, Myocardial infarction, business, Adverse effect, Stroke
Abstract: AIM CHA2 DS2 -VASc score has been proven to have great prognostic value in patients with acute coronary syndrome (ACS). We aimed to determine whether the addition of renal dysfunction in the CHA2 DS2 -VASc score would improve the prognostic impact of the scoring system to predict prognosis among ACS patients. METHODS A total of 3031 ACS patients were prospectively enrolled at 39 hospitals and followed for 1 year. The patients were divided into three groups based on estimated glomerular filtration rate (eGFR) (group 1, eGFR>90; group 2, eGFR between 60 and 90; and group 3, eGFR
Published: 2016

44. Cost-effectiveness of amlodipine compared with valsartan in preventing stroke and myocardial infarction among hypertensive patients in Taiwan

Author: Ruey Tay Lin, Jim Z. Li, Yi-Heng Li, Lung Chan, Kou Gi Shyu, Juey-Jen Hwang, San Jou Yeh, Wen Yi Shau, Larry Z. Liu, Te Chang Weng, and Chen Huan Chen
Subjects: medicine.medical_specialty, Cost effectiveness, International Journal of General Medicine, 030204 cardiovascular system & hematology, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, 030212 general & internal medicine, Amlodipine, Myocardial infarction, Risk factor, Stroke, cost-effectiveness, CCB, health care economics and organizations, Original Research, business.industry, General Medicine, medicine.disease, ARB, Markov model, pharmacoeconomic, Valsartan, Cohort, Medical emergency, business, medicine.drug
Abstract: Lung Chan,1 Chen-Huan Chen,2 Juey-Jen Hwang,3 San-Jou Yeh,4 Kou-Gi Shyu,5 Ruey-Tay Lin,6 Yi-Heng Li,7 Larry Z Liu,8 Jim Z Li,9 Wen-Yi Shau,10 Te-Chang Weng,10 1Department of Neurology, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei, 2Department of Internal Medicine, Faculty of Medicine, National Yang-Ming University, 3Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 4Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, 5Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 6Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, 7Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 8Pfizer Inc, New York, NY, USA; 9Pfizer Inc, San Diego, CA ,USA; 10Pfizer Ltd., New Taipei City, Taiwan Abstract: Hypertension is a major risk factor for strokes and myocardial infarction (MI). Given its effectiveness and safety profile, the calcium channel blocker amlodipine is among the most frequently prescribed antihypertensive drugs. This analysis was conducted to determine the costs and quality-adjusted life years (QALYs) associated with the use of amlodipine and valsartan, an angiotensin II receptor blocker, in preventing stroke and MI in Taiwanese hypertensive patients. A state transition (Markov) model was developed to compare the 5-year costs and QALYs for amlodipine and valsartan. Effectiveness data were based on the NAGOYA HEART Study, local studies, and a published meta-analysis. Utility data and costs of MI and stroke were retrieved from the published literature. Medical costs were based on the literature and inflated to 2011 prices; drug costs were based on National Health Insurance prices in 2014. A 3% discount rate was used for costs and QALYs and a third-party payer perspective adopted. One-way sensitivity and scenario analyses were conducted. Compared with valsartan, amlodipine was associated with cost savings of New Taiwan Dollars (NTD) 2,251 per patient per year: costs were NTD 4,296 and NTD 6,547 per patient per year for amlodipine and valsartan users, respectively. Fewer cardiovascular events were reported in patients receiving amlodipine versus valsartan (342 vs 413 per 10,000 patients over 5 years, respectively). Amlodipine had a net gain of 58 QALYs versus valsartan per 10,000 patients over 5 years. Sensitivity analyses showed that the discount rate and cohort age had a larger effect on total cost and cost difference than on QALYs. However, amlodipine results were more favorable than valsartan irrespective of discount rate or cohort age. When administered to Taiwanese patients for hypertension control, amlodipine was associated with lower cost and more QALYs compared with valsartan due to a lower risk of stroke and MI events. Keywords: cost-effectiveness, pharmacoeconomic, Markov model, CCB, ARB
Published: 2016

45. One-year cardiovascular outcomes of drug-eluting stent versus bare-metal stent implanted in diabetic patients with acute coronary syndrome

Author: Kou-Gi Shyu, Ai-Hsien Li, Guang-Yuan Mar, Shu-Chen Chang, Tsung-Hsien Lin, Chi-Cheng Lai, Chun-Peng Liu, and Hon-Kan Yip
Subjects: Bare-metal stent, Adult, Male, medicine.medical_specialty, Acute coronary syndrome, medicine.medical_treatment, 030204 cardiovascular system & hematology, bare-metal stent, acute coronary syndrome, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, drug-eluting stent, Medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Aged, Medicine(all), lcsh:R5-920, business.industry, Hazard ratio, percutaneous coronary intervention, Percutaneous coronary intervention, Stent, Drug-Eluting Stents, General Medicine, Middle Aged, medicine.disease, Treatment Outcome, Drug-eluting stent, Metals, diabetes mellitus, Cardiology, outcome, Female, Stents, business, lcsh:Medicine (General), Mace
Abstract: Background The outcomes of drug-eluting stent (DES) versus bare-metal stent (BMS) use in patients with diabetic mellitus (DM) and acute coronary syndrome (ACS) are rarely reported in Taiwan. This study aimed to investigate the 1-year cardiovascular outcomes of DESs versus BMSs implanted in Taiwanese patients with DM and ACS. Methods For this study, we collected and analyzed patient information from the database of the Taiwan ACS Full Spectrum registry regarding characteristics and cardiovascular events in participants with DM and ACS who received implantation of either BMS (BMS group) or DES (DES group) from October 2008 to January 2010. Results We found that several characteristics significantly varied between the groups. Compared with the BMS group ( n = 575), the DES group ( n = 199) had significantly lower rates of in-hospital cardiogenic shock (1.5% vs. 4.9%, p = 0.037) and acute renal failure (0.5% vs. 4.5%, p = 0.008), all-cause mortality (5.0% vs. 8.9%, p = 0.048), and major adverse cardiac events (MACEs) at 1 year (11.1% vs. 18.6%, p = 0.006) with an identical target vessel revascularization (TVR) rate (6.0% vs. 7.3%, p = 0.395). The BMS group had significantly higher risk-adjusted all-cause mortality [hazard ratio (HR) = 2.4, 95% confidence interval (CI) 1.0–5.7; p = 0.048] and MACE (HR = 2.2, 95% CI 1.2–3.9; p = 0.011) at 1 year with identical risks of TVR (HR = 1.3, 95% CI 0.6–2.9; p = 0.505) and nonfatal myocardial infarction (HR = 1.5, 95% CI 0.5–4.4; p = 0.478). Conclusion The results of this study support the use of DES over BMS in Taiwanese patients with DM and ACS, providing the clinical benefits of lower rates of total mortality and MACE, and without increased TVR at 1 year in a real-world setting.
Published: 2016
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46. Acute coronary syndrome in the Asia-Pacific region

Author: Young-Hoon Jeong, Mark Y. Chan, Bryan P. Yan, David Eccleston, Changsheng Ma, Manabu Ogita, Xin Du, Kou Gi Shyu, and Padinhare P. Mohanan
Subjects: medicine.medical_specialty, Acute coronary syndrome, Telemedicine, Asia, Acute coronary syndromes, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Patient Education as Topic, Cultural diversity, medicine, Humans, Antiplatelet, Medical management, Registries, 030212 general & internal medicine, Acute Coronary Syndrome, Mortality, Cause of death, Pacific Ocean, business.industry, Asia-Pacific, Guideline, medicine.disease, Metropolitan area, Outreach, Myocardial infarction, Family medicine, Medical emergency, Cardiology and Cardiovascular Medicine, business, Patient education
Abstract: More than 4.2 billion inhabitants populate the Asia-Pacific region. Acute coronary syndrome (ACS) is now a major cause of death and disability in this region with in-hospital mortality typically exceeding 5%. Yet, the region still lacks consensus on the best approach to overcoming its specific challenges in reducing mortality from ACS. The Asia-Pacific Real world evIdenCe on Outcome and Treatment of ACS (APRICOT) project reviewed current published and unpublished registry data, unmet needs in ACS management and possible approaches towards improving ACS-related mortality in the region. There was striking heterogeneity in the use of invasive procedures, pharmacologic practice (hospitalization/post-discharge), and in short- and long-term clinical outcomes across healthcare systems; this heterogeneity was perceived to be far greater than in Western Europe or the United States. ‘Benchmark’ short-term clinical outcomes are preferred over long-term outcomes due to difficulties in follow-up, recording and maintenance of medication adherence in a geographically large and culturally diverse region. Key ‘barriers’ towards improving outcomes include patient education (pain awareness, consequences of missing medication and secondary prevention), geographical landscape (urban vs. metropolitan), limited long-term adherence to guideline-based management and widespread adoption of cost-based rather than value-based healthcare systems. Initiatives to overcome these barriers should include implementation of pre-hospital management strategies, toolkits to aid in-hospital treatment, greater community outreach with online patient/physician education and telemedicine, sustainable economic models to improve accessibility to effective pharmacotherapies and the acquisition of high-quality ‘real-world’ regional data to tailor secondary prevention initiatives that meet the unique needs of countries in this region.
Published: 2016

47. Natural Coumarin Derivative Esculetin Regulates Platelet Activation via Modulating NF-κB Signaling in Cyclic Nucleotide-Independent Manner

Author: Chih Wei Hsia, Marappan Velusamy, Kou Gi Shyu, Thanasekaran Jayakumar, Chih Hsuan Hsia, Joen Rong Sheu, and Chih Hao Yang
Subjects: Pharmacology, 0303 health sciences, Cell, NF-κB, Plant Science, General Medicine, 030204 cardiovascular system & hematology, Coumarin, Cell biology, Nf κb signaling, 03 medical and health sciences, chemistry.chemical_compound, Cyclic nucleotide, 0302 clinical medicine, medicine.anatomical_structure, Complementary and alternative medicine, chemistry, Drug Discovery, medicine, Platelet activation, Derivative (chemistry), 030304 developmental biology
Abstract: Esculetin, a natural coumarin derivative, shows exciting biological activities in a variety of cell and animal models. Our recent study demonstrated that esculetin exhibits antiplatelet effects by obstructing the phospholipase C γ2/protein kinase C cascade, hydroxyl radical formation, and Akt activation. In this study, we further examined the involvement of cyclic 3′-5′adenosine monophosphate/, vasodilator-stimulated phosphoprotein (VASP), integrin αIIbβ3, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), since cyclic nucleotides reduce the phosphorylation of VASP and activate NF-κB, subsequently inducing αIIbβ3 activation that significantly involves the platelet inhibitory pathways. We found that esculetin (50 and 80 µM) did not significantly affect fibrinogen-induced aggregation of elastase-treated platelets; however, it markedly blocked integrin αIIbβ3 activation by interrupting the binding of fluorescein isothiocyanate-labeled PAC-1. In addition, neither ODQ nor SQ22536 significantly reversed esculetin-mediated antiplatelet activity stimulated by collagen. Nitroglycerin and prostaglandin E1 significantly increased VASP phosphorylation, but esculetin had no effect in this reaction, the values being almost identical with those of normal platelets. Furthermore, esculetin, at its maximum concentration of 80 μM significantly reduced the phosphorylation of IκBα and p65 and reversed IκBα degradation in collagen-induced platelets. These results suggest that the NF-κB-dependent αIIbβ3 inhibition of esculetin might represent a novel feedback inhibitory mechanism to regulate platelet functions.
Published: 2019

48. 2018 Expert Consensus on the Management of Adverse Effects of Antiplatelet Therapy for Acute Coronary Syndrome in Taiwan

Author: Yi-Heng, Li, Chih-Yuan, Fang, I-Chang, Hsieh, Wei-Chun, Huang, Tsung-Hsien, Lin, Shih-Hsien, Sung, Chiung-Zuan, Chiu, Chiung-Jen, Wu, Kou-Gi, Shyu, Po-Yuan, Chang, Ching-Chang, Fang, Tse-Min, Lu, Ching-Pei, Chen, Wei-Chen, Tai, Chau-Chyun, Sheu, Kai-Che, Wei, Yi-Hsiu, Huang, Hsing-Mei, Wu, and Juey-Jen Hwang, Hwang
Subjects: Review Article
Abstract: Antiplatelet therapy is a key component in the treatment of acute coronary syndrome (ACS). The management of ACS has evolved considerably over recent years with the development of new and more potent antiplatelet agents. Clinical trials on ACS have demonstrated that potent antiplatelet agents can more effectively reduce cardiovascular events. However, there is a tipping point between safety and efficacy, beyond which the risk of bleeding and other adverse effects can outweigh the benefits of antiplatelet therapy. Striking a balance between safety and efficacy remains a major challenge. A consensus meeting of an expert panel composed of Taiwanese experts was held to provide recommendations for the management of adverse effects in patients with ACS receiving antiplatelet therapy. The common adverse effects of antiplatelet therapy include upper gastrointestinal bleeding, ecchymosis, hematuria, epistaxis and ticagrelor-related dyspnea. In this study, a literature review of these adverse events was performed and recommendations for the management were made.
Published: 2018

49. 2018 consensus of the Taiwan Society of Cardiology and the Diabetes Association of Republic of China (Taiwan) on the pharmacological management of patients with type 2 diabetes and cardiovascular diseases

Author: Chien-Ning Huang, Tsung-Hsien Lin, Yen-Wen Wu, Shih-Yi Lin, Lee-Ming Chuang, Ping Yen Liu, Chia Ti Tsai, Yi-Heng Li, San Jou Yeh, Shing Jong Lin, Kou Gi Shyu, Jung Fu Chen, Hung I. Yeh, Shyi Jang Shin, Wei Hsian Yin, Chern En Chiang, Tzung-Dau Wang, Kwo Chang Ueng, Jiunn Lee Lin, Wayne Huey-Herng Sheu, Hao Min Cheng, Wei-Shiung Yang, Pao-Hsien Chu, Yi Jen Hung, Ting-Hsing Chao, Kuan-Cheng Chang, and Kang Ling Wang
Subjects: medicine.medical_specialty, Consensus, Cardiology, Taiwan, Heart failure, Type 2 diabetes, 030204 cardiovascular system & hematology, Hypoglycemia, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Diabetes mellitus, Internal medicine, Chronic kidney disease, medicine, Humans, Hypoglycemic Agents, 030212 general & internal medicine, Stroke, Societies, Medical, Glycated Hemoglobin, lcsh:R5-920, business.industry, Anti-diabetic agents, General Medicine, medicine.disease, Clinical trial, Coronary heart disease, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Hypertension, business, lcsh:Medicine (General), Kidney disease, Cohort study, Glomerular Filtration Rate
Abstract: The global incidence and prevalence of type 2 diabetes have been escalating in recent decades. Patients with type 2 diabetes have an increased risk of atherosclerotic cardiovascular disease (ASCVD). About two-thirds of death in type 2 diabetes are due to ASCVD, including 40% from coronary heart disease (CHD), 15% from heart failure (HF), and 10% from stroke. The association between hyperglycemia and elevated CV risk has been demonstrated in multiple cohort studies. However, clinical trials of intensive glucose reduction did not significantly reduce macrovascular outcomes. It remains unclear whether the absence of demonstrable benefits is attributed to the inclusion of patients with far advanced ASCVD in whom a short treatment period is barely enough for CV protective effects to be shown, or complications associated with the treatment such as hypoglycemia hamper the beneficial effects to manifest, or simply glucose-lowering per se is ineffective. Since the US FDA issued a mandate in December 2008 that every new anti-diabetic agent requires rigorous assessments of its CV safety, there have been more than 200,000 patients enrolled in a number of randomized controlled trials (RCTs), and around half of them have been completed and published. The results of these CV outcome trials are important for clinicians in their clinical practice, and also provide an opportunity for academic society to formulate treatment guidelines or consensus to provide specific recommendations for glucose control in various CV diseases. The Taiwan Society of Cardiology (TSOC) and the Diabetes Association of Republic of China (DAROC), aiming to formulate a treatment consensus in type 2 diabetic patients with CVD, have appointed a jointed consensus group for the 2018 Consensus of TSOC/DAROC (Taiwan) on the Pharmacological Management of Patients with Type 2 Diabetes and CV Diseases. The consensus is comprised of 5 major parts: 1) Treatment of diabetes in patients with hypertension, 2) Treatment of diabetes in patients with CHD, 3) Treatment of diabetes in patients with stage 3 chronic kidney disease, 4) Treatment of diabetes in patients with a history of stroke, and 5) Treatment of diabetes in patients with HF. The members of the consensus group comprehensively reviewed all the evidence, mainly RCTs, and also included meta-analyses, cohort studies, and studies using claim data. The treatment targets of HbA1c were provided. The anti-diabetic agents were ranked according to their clinical evidence. The consensus is not mandatory. The final decision may need to be individualized and based on clinicians' discretion.
Published: 2018

50. Metformin Was Associated with Lower All-Cause Mortality in Type 2 Diabetes with Acute Coronary Syndrome: A Nationwide Registry with Propensity Score-Matched Analysis

Author: I-Chang Hsieh, Kou-Gi Shyu, Jun-Ted Chong, Mu-Yang Hsieh, Kwo-Chang Ueng, Chao-Lun Lai, Chien-Boon Jong, Kuan-Yu Chen, Wei-Shiang Lin, Fang-Ying Su, Chih-Cheng Wu, Chih-Neng Hsu, and Wen-Chol Voon
Subjects: medicine.medical_specialty, education.field_of_study, business.industry, Mortality rate, Population, Hazard ratio, Retrospective cohort study, Type 2 diabetes, medicine.disease, law.invention, Randomized controlled trial, law, Internal medicine, Propensity score matching, Cohort, medicine, education, business
Abstract: Background: No randomized controlled trials evaluating metformin therapy efficacy in patients with type 2 diabetes mellitus (DM) and acute coronary syndrome (ACS) have been reported. Well-designed retrospective studies controlling for imbalance in baseline patient characteristics are scarce. We aimed to examine the mortality benefit of metformin therapy in patients with type 2 DM and ACS, compared with non-metformin anti-diabetes agent users. Method: Data were extracted from the prospective nationwide ACS-DM Taiwan Society of Cardiology registry. Propensity score (PS) matching on baseline characteristics and treatment measures was performed for metformin versus non-metformin users. Cox proportional hazard models were used to compare mortality outcomes among the PS-matched cohort as a primary analysis. Traditional Cox proportional hazard models adjusting for all pre-determined covariates and quintiles of the PS among the overall population were performed as a secondary analysis. Findings: Of 1157 patients with type 2 DM and ACS receiving anti-diabetes agents, 78 patients (6.7%) died over the 2-year follow-up period. After PS matching, 318 metformin users were matched with 318 non-metformin users. Metformin users had a lower all-cause mortality rate (adjusted hazard ratio [aHR] 0·50, 95% confidence interval [CI] 0·26-0·95) in the primary analysis. The survival benefit of metformin therapy was consistent in the secondary analyses (aHR 0·30, 95% CI 0·17-0·54 while adjusting for all pre-determined covariates, and aHR 0·34, 95% CI 0·19-0·59 while adjusting for quintiles of the PS). Interpretation: Among patients with type 2 DM and ACS, metformin was associated with lower all-cause mortality. Funding Statement: This work was supported with grants from the Hsin-Chu branch of the National Taiwan University Hospital (HCH-106036). The funding source also provided technical help (Biotechnology R&D Center) with data analysis and interpretation of the findings. Declaration of Interest: All authors report no relationships that could be construed as a conflict of interest. Ethics Approval Statement: Patients are treated according to international or local guidelines and evidence-based strategies. The protocol and consent forms used in this study were consistent with the Declaration of Helsinki and relevant regulations. The ethics committees of each participating hospital approved the study, and all enrolled patients provided written informed consent.
Published: 2018

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