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1. Developing a phantom for simulating robotic-assisted complete mesocolic excision using 3D printing and medical imaging

Author

Peter Hertz, Claus Anders Bertelsen, Kim Houlind, Lars Bundgaard, Lars Konge, Flemming Bjerrum, and Morten Bo Søndergaard Svendsen

Subjects
Education, Simulation, Training, Robotic surgery, Complete mesocolic excision, Simulator, Surgery, RD1-811
Abstract

Abstract Background Robotic-assisted complete mesocolic excision is an advanced procedure mainly because of the great variability in anatomy. Phantoms can be used for simulation-based training and assessment of competency when learning new surgical procedures. However, no phantoms for robotic complete mesocolic excision have previously been described. This study aimed to develop an anatomically true-to-life phantom, which can be used for training with a robotic system situated in the clinical setting and can be used for the assessment of surgical competency. Methods Established pathology and surgical assessment tools for complete mesocolic excision and specimens were used for the phantom development. Each assessment item was translated into an engineering development task and evaluated for relevance. Anatomical realism was obtained by extracting relevant organs from preoperative patient scans and 3D printing casting moulds for each organ. Each element of the phantom was evaluated by two experienced complete mesocolic excision surgeons without influencing each other’s answers and their feedback was used in an iterative process of prototype development and testing. Results It was possible to integrate 35 out of 48 procedure-specific items from the surgical assessment tool and all elements from the pathological evaluation tool. By adding fluorophores to the mesocolic tissue, we developed an easy way to assess the integrity of the mesocolon using ultraviolet light. The phantom was built using silicone, is easy to store, and can be used in robotic systems designated for patient procedures as it does not contain animal-derived parts. Conclusions The newly developed phantom could be used for training and competency assessment for robotic-assisted complete mesocolic excision surgery in a simulated setting.

Published
2024
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2. Diabetes and risk of peripheral artery disease in patients undergoing first-time coronary angiography between 2000 and 2012 – a nationwide study

Author

Sadaf Kamil, Thomas S. G. Sehested, Nicholas Carlson, Kim Houlind, Jens F. Lassen, Casper N. Bang, Helena Dominguez, Christian T. Pedersen, and Gunnar H. Gislason

Subjects
Type 2 diabetes mellitus, Peripheral artery disease, Coronary artery disease, Atherosclerosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background The risk of peripheral artery disease (PAD) in patients with diabetes mellitus (DM) and coronary artery disease (CAD) is an important and inadequately addressed issue. Our aim is to examine the impact of DM on risk of PAD in patients with different degrees of CAD characterized by coronary angiography (CAG). Methods Using nationwide registers we identified all patients aged ≥18 years, undergoing first time CAG between 2000 and 2012. Patients were categorized into DM/Non-DM group, and further classified into categories according to the degree of CAD i.e., no-vessel disease, single-vessel disease, double-vessel disease, triple-vessel disease, and diffuse disease. Risk of PAD was estimated by 5-year cumulative-incidence and adjusted multivariable Cox-regression models. Results We identified 116,491 patients undergoing first-time CAG. Among these, a total of 23.969 (20.58%) had DM. Cumulative-incidence of PAD among DM patients vs. non-DM were 8.8% vs. 4.9% for no-vessel disease, 8.2% vs. 4.8% for single-vessel disease, 10.2% vs. 6.0% for double-vessel disease, 13.0% vs. 8.4% for triple-vessel disease, and 6.8% vs. 6.1% for diffuse disease, respectively. For all patients with DM, the cox-regression analysis yielded significantly higher hazards of PAD compared with non-DM patients with HR 1.70 (no-vessel disease), 1.96 (single-vessel disease), 2.35 (double-vessel disease), 2.87 (triple-vessel disease), and 1.46 (diffuse disease), respectively (interaction-p 0.042). Conclusion DM appears to be associated with increased risk of PAD in patients with and without established CAD, with increasing risk in more extensive CAD. This observation indicates awareness on PAD risk in patients with DM, especially among patients with advanced CAD.

Published
2019
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3. Trends in Use of Cardioprotective Medication in Peripheral Artery Disease: A Nationwide Study

Author

Sadaf Kamil, Thomas S. G. Sehested, Kim Houlind, Jens F. Lassen, Gunnar H. Gislason, and Helena Dominguez

Subjects
atrial fibrillation, myocardial infarction, peripheral artery disease, stroke, temporal trends, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Guideline‐based cardioprotective medical therapy is intended to reduce the burden of adverse cardiovascular and limb outcomes in patients with peripheral artery disease (PAD). However, contemporary data describing trends in use of medication remains limited. The present study, therefore, aims to investigate changes in use of cardioprotective medication in PAD. Methods and Results By using Danish national healthcare registries, we identified all patients with first‐time diagnosis of PAD (1997–2016) and classified them into two groups: (1) PAD+ that includes all patients with PAD with a history of cardiovascular disease, ie, myocardial infarction, atrial fibrillation, and stroke (n=162 627); and (2) PAD (n=87 935) that comprise patients without a history of cardiovascular disease. We determined the use of medication in the first 12 months after the incident diagnosis of PAD and estimated age standardized 1‐year mortality rates. Our results showed increase in use of cardioprotective medication throughout the study period in both groups. However, PAD+ had a higher use of medication (acetylsalicylic acid, 3.5%–48.4%; Clopidogrel, 0%–17.6%; vitamin K antagonists, 0.9%–7.8%; new oral anticoagulants, 0.0%–10.1%; Statins, 1.9%–58.1%; angiotensin‐converting enzyme inhibitors, 1.2%–20.6%), compared with PAD (acetylsalicylic acid, 2.9%–54.4%; Clopidogrel, 0%–11.9%; vitamin K antagonists, 0.9%–2.4%; new oral anticoagulants, 0.0%–3.4%; Statins, 1.5%–56.9%; angiotensin‐converting enzyme, 0.9%–17.2%), respectively. Furthermore, 1‐year mortality rates in PAD declined with increased use of medications during study. Conclusions In this nationwide study, use of cardioprotective medication increased considerably with time, but compared to patients with other atherosclerotic diseases, there remains an underuse of guideline‐based medical therapy in patients with PAD.

Published
2021
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4. Quantification of microRNA in plasma using probe based TaqMan assays: is microRNA purification required?

Author

Helle Glud Binderup, Jonna Skov Madsen, Claus Lohman Brasen, Kim Houlind, and Rikke Fredslund Andersen

Subjects
MicroRNA, Direct plasma RT-qPCR, Sample preparation, TaqMan assays, Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
Abstract

Abstract Objective Circulating microRNAs are promising diagnostics and prognostics biomarkers in a wide variety of diseases. However, there is a critical reproducibility challenge, which in part may be due to preanalytical factors. MicroRNA purification has been identified as the major contributor to the total intra assay variation, thus we found great interest in recent papers describing methods for direct quantification of circulating microRNAs without the purification step. With one exception, all the studies we identified where a direct quantification of circulating microRNAs had been performed were using SYBR Green chemistry. In our laboratory we use platelet-poor plasma and TaqMan assays for microRNA analysis, and thus we investigated whether we could adapt the procedures for the direct reverse transcription described by these studies to be used with our TaqMan assays. Results We did not achieve valid results by direct quantification of selected microRNAs (miR-92a, miR-16 and miR-126) in platelet-poor plasma using TaqMan assays.

Published
2019
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5. Time trends in the risk of atrial fibrillation and ischaemic stroke in patients with peripheral artery disease between 1997 and 2015

Author

Gunnar Gislason, Sadaf Kamil, Thomas Sehested, Kim Houlind, Jens Lassen, and Helena Dominguez

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Objective The risk of atrial fibrillation (AF) and stroke in patients with peripheral artery disease (PAD) is an important issue that has not been investigated adequately. Our aim with the present study was to explore trends in the incidence of AF and stroke in patients with PAD.Methods We employed Danish nationwide registers to identify all patients with first-time diagnosis of PAD (aged ≥18 years) between 1997 and 2015. Age-standardised incidence rates per 1 000 person-years were calculated to estimate trends of AF and stroke. Risk of AF and stroke was estimated by 1 year cumulative incidence.Results A total of 121.241 patients with first-time diagnosis of PAD were identified. The 1-year cumulative incidence of AF in patients with PAD were 1.97% for year 1997–2000, 2.63% for year 2001–2005, 2.66% for year 2006–2010 and 2.78% for year 2011–2015, respectively. The 1-year cumulative incidence of stroke in patients with PAD were 2.71%, 2.71%, 1.95% and 1.81%, for the 1997–2000, 2001–2005, 2006–2010 and 2011–2015 year groups, respectively. Likewise, the age-standardised incidence rates showed increasing trends of AF during the study period, whereas trends of stroke demonstrated a decline. During study, the initiation of cholesterol-lowering agents and clopidogrel increased markedly from 7.0% to 51.3% and 0.1% to 5.9%, whereas use of warfarin slightly dropped from 4.29% to 3.21%.Conclusions The incidence of AF in patients with PAD has significantly increased over time, whereas a marked decline has occurred in the incidence of stroke. This may suggest that the secondary prevention strategies aimed at reducing risk of stroke are broadly effective.

Published
2020
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6. Quantification of microRNA levels in plasma - Impact of preanalytical and analytical conditions.

Author

Helle Glud Binderup, Jonna Skov Madsen, Niels Henrik Helweg Heegaard, Kim Houlind, Rikke Fredslund Andersen, and Claus Lohman Brasen

Subjects
Medicine, Science
Abstract

Numerous studies have reported a potential role for circulating microRNAs as biomarkers in a wide variety of diseases. However, there is a critical reproducibility challenge some of which might be due to differences in preanalytical and/or analytical factors. Thus, in the current study we systematically investigated the impact of selected preanalytical and analytical variables on the measured microRNA levels in plasma. Similar levels of microRNA were found in platelet-poor plasma obtained by dual compared to prolonged single centrifugation. In contrast, poor correlation was observed between measurements in standard plasma compared to platelet-poor plasma. The correlation between quantitative real-time PCR and droplet digital PCR was found to be good, contrary to TaqMan Low Density Array and single TaqMan assays where no correlation could be demonstrated. Dependent on the specific microRNA measured and the normalization strategy used, the intra- and inter-assay variation of quantitative real-time PCR were found to be 4.2-6.8% and 10.5-31.4%, respectively. Using droplet digital PCR the intra-assay variation was 4.4-20.1%, and the inter-assay variation 5.7-26.7%. Plasma preparation and microRNA purification were found to account for 39-73% of the total intra-assay variation, dependent on the microRNA measured and the normalization strategy used. In conclusion, our study highlighted the importance of reporting comprehensive methodological information when publishing, allowing others to perform validation studies where preanalytical and analytical variables as causes for divergent results can be minimized. Furthermore, if microRNAs are to become routinely used diagnostic or prognostic biomarkers, the differences in plasma microRNA levels between health and diseased subjects must exceed the high preanalytical and analytical variability.

Published
2018
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7. A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial

Author

Andrew W Bradbury, Catherine A Moakes, Matthew Popplewell, Lewis Meecham, Gareth R Bate, Lisa Kelly, Ian Chetter, Athanasios Diamantopoulos, Arul Ganeshan, Jack Hall, Simon Hobbs, Kim Houlind, Hugh Jarrett, Suzanne Lockyer, Jonas Malmstedt, Jai V Patel, Smitaa Patel, S Tawqeer Rashid, Athanasios Saratzis, Gemma Slinn, D Julian A Scott, Hany Zayed, and Jonathan J Deeks

Subjects
General Medicine
Published
2023

8. A Vein Bypass First Versus a Best Endovascular Treatment First Revascularisation Strategy for Chronic Limb Threatening Ischaemia Requiring an Infra-Popliteal with or Without a More Proximal Procedure to Restore Limb Perfusion: The Bypass Versus Angioplasty for Severe Ischaemia of the Leg (BASIL) 2 Randomised Controlled Trial

Author

Andrew Walter Bradbury, Catherine Hewitt, Matthew Popplewell, Lewis Meecham, Gareth Bate, Lisa Kelly, Ian Chetter, Athansios Diamantopoulos, Arul Ganeshan, Jack Hall, Simon Hobbs, Kim Houlind, Hugh Jarrett, Suzanne Lockyer, Jonas Malmstedt, Jai Patel, Smitaa Patel, S. Tawqeer Rashid, Athanasios Saratzis, Gemma Slinn, David Julian Scott, Hany Zayed, and Jon Deeks

Published
2023

9. Incidence of myocardial infarction, heart failure, and cardiovascular mortality in patients with peripheral artery disease: Trends between 1997 and 2016

Author

Sadaf Kamil, Thomas S G Sehested, Kim Houlind, Jens F Lassen, Gunnar H Gislason, and Helena Dominguez

Subjects
Health Policy, Cardiology and Cardiovascular Medicine
Abstract

Aims Over the past decades, there have been improvements in the management of cardiovascular (CV) disease and risk factors. Long-term contemporary data on the population-level incidence of myocardial infarction (MI), heart failure (HF), and CV mortality in patients with peripheral artery disease (PAD) are sparse, which we aim to investigate in this study. Methods and results Danish nationwide registers were used to identify all patients aged ≥18 years, with first diagnosis of PAD between 1997 and 2016. Age-standardized incidence rates (IRs) per 1000 person-years were calculated to estimate trends of MI, HF, and CV mortality. The risk of MI, HF, and CV mortality was estimated by 1-year cumulative incidence with death as the competing risk. A total of 131 568 patients with PAD were identified [median age 70.67 (interquartile range, IQR, 61–78) years and 53.05% males]. The IRs showed increasing trends of MI until 2002, with an estimated annual percentage change (APC) of + 0.6 [95% confidence interval (CI) 3.3–16.1, P-value 0.2]. After the year 2002, MI incidence persistently decreased until the study end with an estimated APC of −5.0 (95% CI 3.7–6.3, P Conclusion The incidence of MI (since 2002) and HF in patients with PAD has significantly decreased over time, together with a decline in CV mortality. Our results suggest that preventive strategies have overall improved, most likely due to improvements in the application of guidelines in clinical care.

Published
2022

10. Identifying curriculum content for a cross-specialty robotic-assisted surgery training program: a Delphi study

Author

Peter, Hertz, Kim, Houlind, Jan, Jepsen, Lars, Bundgaard, Pernille, Jensen, Mikkel, Friis, Lars, Konge, and Flemming, Bjerrum

Subjects
Surgeons, Delphi Technique, Robotic Surgical Procedures, Humans, Clinical Competence, Curriculum, Robotics
Abstract

Robotic-assisted surgery is increasing and there is a need for a structured and evidence-based curriculum to learn basic robotic competencies. Relevant training tasks, eligible trainees, realistic learning goals, and suitable training methods must be identified. We sought to develop a common curriculum that can ensure basic competencies across specialties.Two robotic surgeons from all departments in Denmark conducting robotic-assisted surgery within gynecology, urology, and gastrointestinal surgery, were invited to participate in a three-round Delphi study to identify learning goals and rank them according to relevance for a basic curriculum. An additional survey was conducted after the Delphi rounds on what training methods were considered best for each learning goal and who (console surgeon/patient-side assistant) should master each learning goal.Fifty-six robotic surgeons participated and the response rates were 86%, 89%, and 77%, for rounds 1, 2 and 3, respectively. The Delphi study identified 40 potential learning goals, of which 29 were ranked as essential, e.g., Understand the link between arm placement and freedom of movement or Be able to perform emergency un-docking. In the additional survey, the response rate was 70%. Twenty-two (55%) of the identified learning goals were found relevant for the patient-side assistant and twenty-four (60%) were linked to a specific suitable learning method with 75% agreement.Our findings can help training centers plan their training programs concerning educational content and methods for training/learning. Furthermore, patient-side assistants should also receive basic skills training in robotic surgery.

Published
2021

11. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial

Author

Sonia S Anand, Jackie Bosch, John W Eikelboom, Stuart J Connolly, Rafael Diaz, Peter Widimsky, Victor Aboyans, Marco Alings, Ajay K Kakkar, Katalin Keltai, Aldo P Maggioni, Basil S Lewis, Stefan Störk, Jun Zhu, Patricio Lopez-Jaramillo, Martin O'Donnell, Patrick J Commerford, Dragos Vinereanu, Nana Pogosova, Lars Ryden, Keith A A Fox, Deepak L Bhatt, Frank Misselwitz, John D Varigos, Thomas Vanassche, Alvaro A Avezum, Edmond Chen, Kelley Branch, Darryl P Leong, Shrikant I Bangdiwala, Robert G Hart, Salim Yusuf, JORGELINA SALA, LUIS CARTASEGNA, MARISA VICO, MIGUEL ANGEL HOMINAL, EDUARDO HASBANI, ALBERTO CACCAVO, CESAR ZAIDMAN, DANIEL VOGEL, ADRIAN HRABAR, PABLO OMAR SCHYGIEL, CARLOS CUNEO, HUGO LUQUEZ, IGNACIO J. MACKINNON, RODOLFO ANDRES AHUAD GUERRERO, JUAN PABLO COSTABEL, INES PALMIRA BARTOLACCI, OSCAR MONTANA, MARIA BARBIERI, OSCAR GOMEZ VILAMAJO, RUBEN OMAR GARCIA DURAN, LILIA BEATRIZ SCHIAVI, MARCELO GARRIDO, ADRIAN INGARAMO, ANSELMO PAULINO BORDONAVA, MARIA JOSE PELAGAGGE, LEONARDO NOVARETTO, JUAN PABLO ALBISU DI GENNERO, LUZ MARIA IBANEZ SAGGIA, MOIRA ALVAREZ, NESTOR ALEJANDRO VITA, STELLA MARIS MACIN, RICARDO DARIO DRAN, MARCELO CARDONA, LUIS GUZMAN, RODOLFO JUAN SARJANOVICH, JESUS CUADRADO, SEBASTIAN NANI, MARCOS RAUL LITVAK BRUNO, CAROLINA CHACON, LAURA ELENA MAFFEI, DIEGO GRINFELD, NATALIA VENSENTINI, CLAUDIO RODOLFO MAJUL, HECTOR LUCAS LUCIARDI, PATRICIA DEL CARMEN GONZALEZ COLASO, FREDY ANTONI FERRE PACORA, PAUL VAN DEN HEUVEL, PETER VERHAMME, BAVO ECTOR, PHILIPPE DEBONNAIRE, PHILIPPE VAN DE BORNE, JEAN LEROY, HERMAN SCHROE, PASCAL VRANCKX, IVAN ELEGEERT, ETIENNE HOFFER, KARL DUJARDIN, CLARISSE INDIO DO BRASIL, DALTON PRECOMA, JOSE ANTONIO ABRANTES, EULER MANENTI, GILMAR REIS, JOSE SARAIVA, LILIA MAIA, MAURO HERNANDES, PAULO ROSSI, FABIO ROSSI DOS SANTOS, SERGIO LUIZ ZIMMERMANN, RAFAEL RECH, EDUARDO ABIB JR, PAULO LEAES, ROBERTO BOTELHO, OSCAR DUTRA, WEIMAR SOUZA, MARIA BRAILE, NILO IZUKAWA, JOSE CARLOS NICOLAU, LUIZ FERNANDO TANAJURA, CARLOS VICENTE SERRANO JUNIOR, CESAR MINELLI, LUIZ ANTONIO NASI, LIVIA OLIVEIRA, MARCELO JOSE DE CARVALHO CANTARELLI, RICHARD TYTUS, SHEKHAR PANDEY, EVA LONN, JAMES CHA, SAUL VIZEL, MOHAN BABAPULLE, ANDRE LAMY, KEVIN SAUNDERS, JOSEPH BERLINGIERI, BOB KIAII, RAKESH BHARGAVA, PRAVINSAGAR MEHTA, LAURIE HILL, DAVID FELL, ANDY LAM, FAISAL AL-QOOFI, CRAIG BROWN, ROBERT PETRELLA, JOSEPH A RICCI, ANTHONY GLANZ, NICOLAS NOISEUX, KEVIN BAINEY, FATIMA MERALI, MICHAEL HEFFERNAN, ANTHONY DELLA SIEGA, GILLES R DAGENAIS, FRANCOIS DAGENAIS, STEEVE BRULOTTE, MICHEL NGUYEN, MICHAEL HARTLEIB, RANDOLPH GUZMAN, RONALD BOURGEOIS, DENNIS RUPKA, YAARIV KHAYKIN, GILBERT GOSSELIN, THAO HUYNH, CLAUDE PILON, JEAN CAMPEAU, FRANCIS PICHETTE, ARIEL DIAZ, JAMES JOHNSTON, PRAVIN SHUKLE, GREGORY HIRSCH, PAUL RHEAULT, WLODZIMIERZ CZARNECKI, ANNIE ROY, SHAH NAWAZ, STEPHEN FREMES, DINKAR SHUKLA, GABRIEL JANO, JORGE LEONARDO COBOS, RAMON CORBALAN, MARCELO MEDINA, LEONARDO NAHUELPAN, CARLOS RAFFO, LUIS PEREZ, SERGIO POTTHOFF, BENJAMIN STOCKINS, PABLO SEPULVEDA, CHRISTIAN PINCETTI, MARGARITA VEJAR, HONGYAN TIAN, XUESI WU, YUANNAN KE, KAIYING JIA, PENGFEI YIN, ZHAOHUI WANG, LITIAN YU, SHULIN WU, ZONGQUI WU, SHAO WEN LIU, XIAO JUAN BAI, YANG ZHENG, PING YANG, YUN MEI YANG, JIWEI ZHANG, JUNBO GE, XIAO PING CHEN, JUNXIA LI, TAO HONG HU, RUIYAN ZHANG, ZHE ZHENG, XIN CHEN, LIANG TAO, JIANPING LI, WEIJIAN HUANG, GUOSHENG FU, CHUNJIAN LI, YUGANG DONG, CHUNSHENG WANG, XINMIN ZHOU, YE KONG, ARISTIDES SOTOMAYOR, JOSE LUIS ACCINI MENDOZA, HENRY CASTILLO, MIGUEL URINA, GUSTAVO AROCA, MARITZA PEREZ, DORA INES MOLINA DE SALAZAR, GREGORIO SANCHEZ VALLEJO, MANZUR J FERNANDO, HENRY GARCIA, LUIS HERNANDO GARCIA, EDGAR ARCOS, JUAN GOMEZ, FRANCISCO CUERVO MILLAN, FREDY ALBERTO TRUJILLO DADA, BORIS VESGA, GUSTAVO ADOLFO MORENO SILGADO, EVA ZIDKOVA, JEAN-CLAUDE LUBANDA, MARKETA KALETOVA, RADIM KRYZA, GABRIEL MARCINEK, MAREK RICHTER, JINDRICH SPINAR, JIRI MATUSKA, MARTIN TESAK, ZUZANA MOTOVSKA, MARIAN BRANNY, JIRI MALY, MARTIN MALY, MARTIN WIENDL, LENKA FOLTYNOVA CAISOVA, JOSEF SLABY, PETR VOJTISEK, JAN PIRK, LENKA SPINAROVA, MIROSLAVA BENESOVA, JULIA CANADYOVA, MIROSLAV HOMZA, JINDRICH FLORIAN, ROSTISLAV POLASEK, ZDENEK COUFAL, VLADIMIRA SKALNIKOVA, RADIM BRAT, MIROSLAV BRTKO, PETR JANSKY, JAROSLAV LINDNER, PAVEL MARCIAN, ZBYNEK STRAKA, MARTIN TRETINA, YAN CARLOS DUARTE, FREDDY POW CHON LONG, MAYRA SANCHEZ, JOSE LOPEZ, CARMITA PERUGACHI, RICARDO MARMOL, FREDDY TRUJILLO, PABLO TERAN, JAAKKO TUOMILEHTO, HENRI TUOMILEHTO, MARJA-LEENA TUOMINEN, ILKKA KANTOLA, GABRIEL STEG, VICTOR ABOYANS, FLORENCE LECLERCQ, EMILE FERRARI, FRANCK BOCCARA, EMMANUEL MESSAS, PATRICK MISMETTI, MARIE ANTOINETTE SEVESTRE, GUILLAUME CAYLA, PASCAL MOTREFF, STEFAN STOERK, HANS-DIRK DUENGEN, CHRISTOPH STELLBRINK, OSMAN GUEROCAK, CHRISTOPH KADEL, RUEDIGER BRAUN-DULLAEUS, MICHAEL JESERICH, CHRISTIAN OPITZ, HANS-FRIEDRICH VOEHRINGER, KARL-FRIEDRICH APPEL, BERNHARD WINKELMANN, THOMAS DORSEL, SIGRID NIKOL, HARALD DARIUS, JURGEN RANFT, SEBASTIAN SCHELLONG, WOLFGANG JUNGMAIR, PIROZE DAVIERWALA, MARC VORPAHL, LASZLO BAJNOK, ZOLTAN LASZLO, EBRAHIM NOORI, GABOR VERESS, ANDRAS VERTES, ANDRAS ZSARY, ERNO KIS, LASZLO KORANYI, JUDIT BAKAI, ZOLTAN BODA, FERENC POOR, ZOLTAN JARAI, VENDEL KEMENY, JOHN BARTON, BRENDAN MCADAM, ANDREW MURPHY, PETER CREAN, NIALL MAHON, RONAN CURTIN, BRIAIN MACNEILL, SEAN DINNEEN, MAJDI HALABI, REUVEN ZIMLICHMAN, DAVID ZELTSER, YOAV TURGEMAN, ELIEZER KLAINMAN, BASIL LEWIS, AMOS KATZ, SHAUL ATAR, EUGENIA NIKOLSKY, STEFANO BOSI, MONICA NALDI, POMPILIO FAGGIANO, DEBORA ROBBA, LUCIO MOS, GIANFRANCO SINAGRA, FRANCO COSMI, LUIGI OLTRONA VISCONTI, DE MATTEIS CARMINE, GIUSEPPE DI PASQUALE, MATTEO DI BIASE, SARA MANDORLA, MARINO BERNARDINANGELI, GIOVANNI CARLO PICCINNI, MICHELE MASSIMO GULIZIA, MARCELLO GALVANI, FLAVIO VENTURI, GIORGIO MOROCUTTI, MARIA GRAZIA BALDIN, CARLO OLIVIERI, GIAN PIERO PERNA, VINCENZO CIRRINCIONE, TAKAYASU KANNO, HIROYUKI DAIDA, YUKIO OZAKI, NAOMASA MIYAMOTO, SHINICHI HIGASHIUE, HIROSHI DOMAE, SHINOBU HOSOKAWA, HIROO KOBAYASHI, TAKEHIKO KURAMOCHI, KENSHI FUJII, KAZUAKI MIZUTOMI, KEIJIRO SAKU, KAZUO KIMURA, YOSHIHARU HIGUCHI, MITSUNORI ABE, HARUHITO OKUDA, TOSHIYUKI NODA, TERUAKI MITA, ATSUSHI HIRAYAMA, HARUHIKO ONAKA, MORIAKI INOKO, MITSUGU HIROKAMI, MUNENORI OKUBO, YUTAKA AKATSUKA, MIZUHO IMAMAKI, HARUO KAMIYA, MAMORU MANITA, TOSHIHARU HIMI, HIDEKI UENO, YUJI HISAMATSU, JUNYA AKO, YASUHIRO NISHINO, HIDEO KAWAKAMI, YUTAKA YAMADA, YUKIHIRO KORETSUNE, TAKAHISA YAMADA, TETSURO YOSHIDA, HIDEKI SHIMOMURA, NORIYUKI KINOSHITA, AKIHIKO TAKAHASHI, KHALID YUSOFF, WAN AZMAN WAN AHMAD, MUHAMMAD RADZI ABU HASSAN, SAZZLI KASIM, AIZAI AZAN ABDUL RAHIM, DIMON MOHD ZAMRIN, MASAHARU MACHIDA, YORIHIKO HIGASHINO, NORIAKI UTSU, AKIHIKO NAKANO, SHIGERU NAKAMURA, TETSUO HASHIMOTO, KENJI ANDO, TOMOHIRO SAKAMOTO, F.J. PRINS, DIRK LOK, JOHANNES GERT-JAN MILHOUS, ERIC VIERGEVER, FRANK WILLEMS, HENK SWART, MARCO ALINGS, ROB BREEDVELD, KEES-JAN DE VRIES, ROGER VAN DER BORGH, FANNY OEI, STIENEKE ZOET-NUGTEREN, HANS KRAGTEN, JEAN PAUL HERRMAN, PAUL VAN BERGEN, MARCEL GOSSELINK, EDUARD HOEKSTRA, ERWIN ZEGERS, EELKO RONNER, FRANK DEN HARTOG, GERARD BARTELS, PETER NIEROP, COEN VAN DER ZWAAN, JACOB VAN ECK, EDWIN VAN GORSELEN, BJORN GROENEMEIJER, PIETER HOOGSLAG, MARC ROBERT DE GROOT, ALDRIN LOYOLA, DENNIS JOSE SULIT, NANNETTE REY, MARIA TERESA ABOLA, DANTE MORALES, ELLEN PALOMARES, MARC EVANS ABAT, GREGORIO ROGELIO, PHILIP CHUA, JOSE CARLO DEL PILAR, JOHN DENNIS ALCARAZ, GERALDINE EBO, LOUIE TIRADOR, JOSEFINA CRUZ, JOHN ANONUEVO, ARTHUR PITARGUE, MARIANNA JANION, TOMASZ GUZIK, GRZEGORZ GAJOS, MACIEJ ZABOWKA, ANDRZEJ RYNKIEWICZ, MARLENA BRONCEL, ANDRZEJ SZUBA, DANUTA CZARNECKA, PAWEL MAGA, IRINA STRAZHESKO, YURY VASYUK, ZHANNA SIZOVA, YURY POZDNYAKOV, OLGA BARBARASH, MIKHAIL VOEVODA, TATIANA POPONINA, ALEXEY REPIN, IRINA OSIPOVA, ANNA EFREMUSHKINA, NINA NOVIKOVA, OLEG AVERKOV, DMITRY ZATEYSHCHIKOV, ARKADIY VERTKIN, AZA AUSHEVA, PATRICK COMMERFORD, SAADIYA SEEDAT, LOUIS VAN ZYL, JAN ENGELBRECHT, ELLEN MAKONLI MAKOTOKO, CATHARINA ELIZABETH PRETORIUS, ZAID MOHAMED, ADRIAN HORAK, THOMAS MABIN, ERIC KLUG, JANG-HO BAE, CHEOLHO KIM, CHONG-JIN KIM, DONG-SOO KIM, YONG JIN KIM, SEUNGJAE JOO, JONG-WON HA, CHUL SOO PARK, JANG YOUNG KIM, YOUNG-KWON KIM, CHRISTINA JARNERT, THOMAS MOOE, MIKAEL DELLBORG, INGEMAR TORSTENSSON, PER ALBERTSSON, LARS JOHANSSON, FARIS AL-KHALILI, HENRIK ALMROTH, TOMMY ANDERSSON, EMIL PANTEV, BENGT-OLOV TENGMARK, BO LIU, GUNDARS RASMANIS, CARL-MAGNUS WAHLGREN, TIZIANO MOCCETTI, ALEXANDER PARKHOMENKO, VIRA TSELUYKO, VOLODYMYR VOLKOV, OLENA KOVAL, LYUDMYLA KONONENKO, OLEKSANDR PROKHOROV, VALERIY VDOVYCHENKO, ANDRIY BAZYLEVYCH, LEONID RUDENKO, VADYM VIZIR, OLEKSANDR KARPENKO, YAROSLAV MALYNOVSKY, VALENTYNA KOVAL, BORYS STOROZHUK, JAMES COTTON, ASOK VENKATARAMAN, ANDREW MORIARTY, DEREK CONNOLLY, PATRICK DAVEY, ROXY SENIOR, INDERPAUL BIRDI, JOHN CALVERT, PATRICK DONNELLY, JASPER TREVELYAN, JUSTIN CARTER, AARON PEACE, DAVID AUSTIN, NEVILLE KUKREJA, THOMAS HILTON, SUNNY SRIVASTAVA, RONALD WALSH, RONALD FIELDS, JOSEPH HAKAS, EDWARD PORTNAY, HARINDER GOGIA, ABRAHAM SALACATA, JOHN J. HUNTER, J MICHAEL BACHARACH, NICOLAS SHAMMAS, DAMODHAR SURESH, RICKY SCHNEIDER, PAUL GURBEL, SUBHASH BANERJEE, PAUL GRENA, NOEL BEDWELL, STEPHEN SLOAN, STEVEN LUPOVITCH, ANAND SONI, KATHLEEN GIBSON, RENEE SANGRIGOLI, RAJENDRA MEHTA, PETER I-HSUAN TSAI, EVE GILLESPIE, STEPHEN DEMPSEY, GLENN HAMROFF, ROBERT BLACK, ELLIS LADER, JOHN B. KOSTIS, VERA BITTNER, WILLIAM MCGUINN, KELLEY BRANCH, VINAY MALHOTRA, STEPHEN MICHAELSON, MICHAEL VACANTE, MATTHEW MCCORMICK, RALUCA ARIMIE, ALAN CAMP, GEORGE DAGHER, N. MATHEW KOSHY, STEPHEN THEW, FREDERICK COSTELLO, MARK HEIMAN, ROBERT CHILTON, MICHAEL MORAN, FREDRIC ADLER, ANTHONY COMEROTA, ANDREW SEIWERT, WILLIAM FRENCH, HARVEY SEROTA, ROBERT HARRISON, FAISAL BAKAEEN, SHUAB OMER, LOKESH CHANDRA, ALAN WHELAN, ANDREW BOYLE, PHILIP ROBERTS-THOMSON, JAMES ROGERS, PATRICK CARROLL, DAVID COLQUHOUN, JAMES SHAW, PETER BLOMBERY, JOHN AMERENA, CHRIS HII, ALISTAIR ROYSE, BHUWAN SINGH, JOSEPH SELVANAYAGAM, SHIRLEY JANSEN, WINGCHI LO, CHRISTOPHER HAMMETT, ROHAN POULTER, SESHASAYEE NARASIMHAN, HENRIK WIGGERS, HENRIK NIELSEN, GUNNAR GISLASON, LARS KOBER, KIM HOULIND, VIBEKE BOENELYKKE SOERENSEN, ULRIK DIXEN, JENS REFSGAARD, ELISABETH ZEUTHEN, PETER SOEGAARD, MARIAN HRANAI, LUDOVIT GASPAR, DANIEL PELLA, KATARINA HATALOVA, ERIKA DROZDAKOVA, IOAN COMAN, DOINA DIMULESCU, DRAGOS VINEREANU, MIRCEA CINTEZA, CRINA SINESCU, CATALINA ARSENESCU, IMRE BENEDEK, ELENA BOBESCU, DAN DOBREANU, DAN GAITA, ADRIAN IANCU, ADRIANA ILIESIU, DANIEL LIGHEZAN, LUCIAN PETRESCU, OCTAVIAN PIRVU, IULIA TEODORESCU, DAN TESLOIANU, MARIUS MARCIAN VINTILA, OVIDIU CHIONCEL, Divisions of Cardiology and Thromboembolism McMaster University Hamiton, Population Health Research Institute, McMaster University [Hamilton, Ontario], Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Research Center [Associazione Nazionale Medici Cardiologi Ospedalieri] (ANMCO Research Center), Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO), Department of Statistics, University of Haifa [Haifa], Cardiology, University and Emergency Hospital, University of Edinburgh, VA Boston Healthcare System, Hamilton General Hospital, Universidad Autonoma de Madrid (UAM), Cardiology Department, Dipartimento di Bioscienze, University of Parma, University of Barcelona, Hospital Clinic Barcelona, Laval University and Hospital Heart and Lung Institute, UVSQ - UFR des sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University Hospital Brno, Masaryk University, Department of Public Health, Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Pasteur [Nice] (CHU), Service de Cardiologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), CHU Gabriel Montpied (CHU), CHU Clermont-Ferrand, Department of Medicine (DEBRECEN - Dpt Medicine), University of Debrecen, University of Trieste, Lab Dev Cell Biol,Bunkyo Ku, The University of Tokyo, The Netherlands Organisation for Applied Scientific Research (TNO), Regional Specialist Hospital in Wroclaw, Research and Development Centre, Kamienskiego, Division of Angiology, Wroclaw Medical University, Sahlgrenska University Hospital/Östra, Cardiocentro Ticino [Lugano], University of Zürich [Zürich] (UZH), Danylo Halytskyi Lviv National Medical University, Department of Cardiology, Sandwell General Hospital, Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Rigshospitalet [Copenhagen], Université de Médecine Carol Davila, Cardiology Department [Târgu Mureș], University of Medicine and Pharmacy of Târgu Mureș, Institute for Cardiovascular Diseases C.C. Iliescu, Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), University of Parma = Università degli studi di Parma [Parme, Italie], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), 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), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Gabriel Montpied [Clermont-Ferrand], The University of Tokyo (UTokyo), Universität Zürich [Zürich] = University of Zurich (UZH), and Copenhagen University Hospital

Subjects
Carotid Artery Diseases, Male, Myocardial Infarction, MESH: Lower Extremity, 030204 cardiovascular system & hematology, THERAPY, Stroke/epidemiology, MESH: Dose-Response Relationship, Drug, 0302 clinical medicine, Rivaroxaban, prevention, Hemorrhage/chemically induced, MESH: Peripheral Arterial Disease, MESH: Double-Blind Method, guidelines, MESH: Incidence, 030212 general & internal medicine, Cardiovascular Diseases/mortality, risk, RISK, MESH: Aged, MESH: Middle Aged, Incidence, General Medicine, Middle Aged, 3. Good health, Stroke, MESH: Myocardial Infarction, Lower Extremity, Cardiovascular Diseases, MESH: Platelet Aggregation Inhibitors, Factor Xa Inhibitors/administration & dosage, Drug Therapy, Combination, Female, MESH: Factor Xa Inhibitors, OUTPATIENTS, MESH: Rivaroxaban, management, MESH: Hemorrhage, metaanalysis, Lower Extremity/blood supply, Rivaroxaban/administration & dosage, Hemorrhage, MESH: Drug Administration Schedule, Amputation, Surgical, Drug Administration Schedule, MESH: Stroke, Peripheral Arterial Disease, 03 medical and health sciences, Double-Blind Method, atherothrombosis, Myocardial Infarction/epidemiology, MANAGEMENT, Humans, MESH: Amputation, MESH: Aspirin, Aspirin/administration & dosage, Platelet Aggregation Inhibitors/administration & dosage, METAANALYSIS, Aged, MESH: Humans, Aspirin, Dose-Response Relationship, Drug, MESH: Carotid Artery Diseases, MORTALITY, MESH: Cardiovascular Diseases, cardiovascular event rates, PREVENTION, CARDIOVASCULAR EVENT RATES, MESH: Male, outpatients, atrial-fibrillation, MESH: Drug Therapy, Combination, MESH: Morbidity, Carotid Artery Diseases/complications, lower-extremity amputation, Peripheral Arterial Disease/complications, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Morbidity, MESH: Female, Platelet Aggregation Inhibitors, Amputation/statistics & numerical data, Factor Xa Inhibitors
Abstract

BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.FUNDING: Bayer AG.

Published
2018

12. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease

Author

Stephane Ederhy, Gilmar Reis, Andrzej Rynkiewicz, Keith Fox, Luca Padua, Helene ABERGEL, Andrew Murphy, Andrzej Szuba, YAN CARLOS DUARTE VERA, Pawel Maga, Scott Berkowitz, Roxana Buzas, Alexey Repin, Gregory Ducrocq, Olga Barbarash, Anton Sadomov, Grzegorz Gajos, Miguel Urina, David McEneaney, Richard Tytus, Dmitriy Panov, Angelika Chachaj, Weimar Kunz Sebba Barroso Souza, Akihiko Takahashi, Salim Yusuf, Mpiko Ntsekhe, Elena Gromova, David Halon, Richard Cheng, Marcello Galvani, Rohan Poulter, JUAN PABLO YEPEZ ALVARAN, Sara Doimo, Kim Houlind, Marcelo Arruda Nakazone, Avinainder Singh, Fabrice Martens, Aldo Pietro Maggioni, Fredrik Folke, Miroslav Brtko, Peter Verhamme, Laszlo Koranyi, Bart Meuris, ALVARO AVEZUM, Boris Vesga, Cyrille Boulogne, Peter Sinnaeve, Zhanna Sizova, Marianna Janion, Crina Julieta Sinescu, Laurent BERTOLETTI, Susanne Brenner, Jaroslav Hlubocký, ELENA BOBESCU, Michelle Canavan, Kamil Bury, Elena Nalesnik, Robert Mikulik, Yaroslav Malynovsky, Liudmyla Parkhomenko, Andrea Barbieri, Philippe Gabriel STEG, Kelley Branch, Olga Shestakovska, Jan Fedacko, Khairul Shafiq Ibrahim, Nicolae-Dan Tesloianu, Daniel Pella, Paul Fedak, Pavel Kaplan, Shirley Jansen, Martin O'Donnell, Marlena Broncel, Fernando Lanas, Stefan Störk, Natalia Garganeeva, Heyman Luckraz, CARLOS AUGUSTO CELEMIN FLOREZ, Larysa Mishchenko, Amos Katz, Jaroslava Paulasova Schwabova, Patricio Lopez-Jaramillo, Gustavo Aroca, Monika Możdżan, Zoltan Varallyay, María José Paucar, Tim Ramsay, Fernando Botto, Muhammad Imran Abdul Hafidz, Juan Esteban Gómez-Mesa, Kaijian Hou, Miroslav Spacek, Tomasz Guzik, Diego Rizzotti, Jackie Bosch, Shrikant Bangdiwala, Robert Welsh, Vojtěch Novotný, Andriy Bazylevych, Niall Mahon, Serhii Serik, Irina PARVU, Daniel Turek, Laurent Feldman, Dmitry Zateyshchikov, Mykola Bychkov, Yury Vasyuk, Camilo Felix, James Cotton, DHAYRA KAREM BARRETO, Sergey Kozhukhov, Sergio Zimmermann, Whady Hueb, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Biomedical Engineering and Physics, Other departments, ACS - Amsterdam Cardiovascular Sciences, Pulmonology, Graduate School, Radiology and Nuclear Medicine, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Male, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, Rivaroxaban, Randomized controlled trial, law, Hemorrhage/chemically induced, Secondary Prevention, Atherosclerosis/complications, 030212 general & internal medicine, Myocardial infarction, Factor Xa Inhibitors/adverse effects, Rivaroxaban/adverse effects, Stroke, risk, Aspirin, oral rivaroxaban, Research Support, Non-U.S. Gov't, Hazard ratio, General Medicine, Middle Aged, trial, Clopidogrel, 3. Good health, Multicenter Study, Cardiovascular Diseases, Randomized Controlled Trial, Platelet aggregation inhibitor, Drug Therapy, Combination, Female, secondary prevention, medicine.drug, Platelet Aggregation Inhibitors/adverse effects, medicine.medical_specialty, venous thromboembolism, Hemorrhage, Aspirin/adverse effects, 03 medical and health sciences, Secondary Prevention/methods, Double-Blind Method, Internal medicine, Journal Article, medicine, Humans, Aged, clopidogrel, business.industry, ta3121, Atherosclerosis, atherothrombotic events, medicine.disease, Surgery, Cardiovascular Diseases/drug therapy, business, Platelet Aggregation Inhibitors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Factor Xa Inhibitors
Abstract

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention.METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months.RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; PCONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

Published
2017

13. [Rehabilitation and palliative care in cardiovascular diseases in Denmark]

Author

Ann Dorthe, Olsen Zwisler, Vicky L, Joshi, Anne Merete, Boas Soja, Vibeke Brogaard, Hansen, Kim, Houlind, Britt, Borregaard, Mette Merlin, Husted, Claus, Engstrup, Amalie Martinus, Hauge, Grete, Broholt, and Lars Hermann, Tang

Subjects
Heart Failure, Cardiovascular Diseases, Denmark, Palliative Care, Humans, Coronary Disease
Abstract

An increasing number of Danes are living, and dying, with cardiovascular disease. There is good evidence for the impact of cardiac rehabilitation on coronary heart disease, heart failure and symptomatic peripheral arterial disease. However, more high-quality research is needed into a wider range of cardiac diseases including rehabilitation following cardiac arrest, and palliative care for patients with advanced heart disease. In this review it is discussed how to improve the quality of care and identify the direction of future research and development.

Published
2018

14. Quantification of circulating microRNA using single TaqMan assays v1

Author

Helle Glud Binderup, Jonna Skov Madsen, Kim Houlind, Rikke Fredslund Andersen, and Claus Lohman Brasen

Subjects
Circulating MicroRNA, TaqMan, Biology, Molecular biology
Abstract

A protocol for quantification of circulating microRNA using TaqMan assays. MicroRNAs are purified from platelet-poor plasma using Nucleospin columns During the purification step samples are spiked with cel-miR-39 as a mean of technical normalization Normalization is performed using the ΔCt-method

Published
2018

15. Quantification of circulating microRNA using droplet digital PCR v1

Author

Helle Glud Binderup, Jonna Skov Madsen, Kim Houlind, Rikke Fredslund Andersen, and Claus Lohman Brasen

Subjects
Circulating MicroRNA, Chemistry, Digital polymerase chain reaction, Molecular biology
Abstract

A protocol for quantification of circulating microRNA using droplet digital PCR with TaqMan assays. MicroRNAs are purified from platelet-poor plasma using Nucleospin columns During the purification step samples are spiked with cel-miR-39 as a mean of technical normalization Normalization are performed by calculating the relative concentration of the target microRNA and the reference.

Published
2018

16. Quantification of circulating microRNA using TaqMan Low Density Array (TLDA) v1

Author

Helle Glud Binderup, Jonna Skov Madsen, Kim Houlind, Rikke Fredslund Andersen, and Claus Lohman Brasen

Abstract

A protocol for quantification of circulating microRNA using TaqMan Low Density Array. MicroRNAs are purified from platelet-poor plasma using Nucleospin columns During the purification step samples are spiked with cel-miR-39 as a mean of technical normalization Normalization is performed using the ΔCt-method

Published
2018

17. Rivaroxaban with or without aspirin in patients with stable coronary artery disease : an international, randomised, double-blind, placebo-controlled trial

Author

Stuart J Connolly, John W Eikelboom, Jackie Bosch, Gilles Dagenais, Leanne Dyal, Fernando Lanas, Kaj Metsarinne, Martin O'Donnell, Anthony L Dans, Jong-Won Ha, Alexandr N Parkhomenko, Alvaro A Avezum, Eva Lonn, Liu Lisheng, Christian Torp-Pedersen, Petr Widimsky, Aldo P Maggioni, Camilo Felix, Katalin Keltai, Masatsugu Hori, Khalid Yusoff, Tomasz J Guzik, Deepak L Bhatt, Kelley R H Branch, Nancy Cook Bruns, Scott D Berkowitz, Sonia S Anand, John D Varigos, Keith A A Fox, Salim Yusuf, JORGELINA SALA, LUIS CARTASEGNA, MARISA VICO, MIGUEL ANGEL HOMINAL, EDUARDO HASBANI, ALBERTO CACCAVO, CESAR ZAIDMAN, DANIEL VOGEL, ADRIAN HRABAR, PABLO OMAR SCHYGIEL, CARLOS CUNEO, HUGO LUQUEZ, IGNACIO J. MACKINNON, RODOLFO ANDRES AHUAD GUERRERO, JUAN PABLO COSTABEL, INES PALMIRA BARTOLACCI, OSCAR MONTANA, MARIA BARBIERI, OSCAR GOMEZ VILAMAJO, RUBEN OMAR GARCIA DURAN, LILIA BEATRIZ SCHIAVI, MARCELO GARRIDO, ADRIAN INGARAMO, ANSELMO PAULINO BORDONAVA, MARIA JOSE PELAGAGGE, LEONARDO NOVARETTO, JUAN PABLO ALBISU DI GENNERO, LUZ MARIA IBANEZ SAGGIA, MOIRA ALVAREZ, NESTOR ALEJANDRO VITA, STELLA MARIS MACIN, RICARDO DARIO DRAN, MARCELO CARDONA, LUIS GUZMAN, RODOLFO JUAN SARJANOVICH, JESUS CUADRADO, SEBASTIAN NANI, MARCOS RAUL LITVAK BRUNO, CAROLINA CHACON, LAURA ELENA MAFFEI, DIEGO GRINFELD, NATALIA VENSENTINI, CLAUDIO RODOLFO MAJUL, HECTOR LUCAS LUCIARDI, PATRICIA DEL CARMEN GONZALEZ COLASO, FREDY ANTONI FERRE PACORA, PAUL VAN DEN HEUVEL, PETER VERHAMME, BAVO ECTOR, PHILIPPE DEBONNAIRE, PHILIPPE VAN DE BORNE, JEAN LEROY, HERMAN SCHROE, PASCAL VRANCKX, IVAN ELEGEERT, ETIENNE HOFFER, KARL DUJARDIN, CLARISSE INDIO DO BRASIL, DALTON PRECOMA, JOSE ANTONIO ABRANTES, EULER MANENTI, GILMAR REIS, JOSE SARAIVA, LILIA MAIA, MAURO HERNANDES, PAULO ROSSI, FABIO ROSSI DOS SANTOS, SERGIO LUIZ ZIMMERMANN, RAFAEL RECH, EDUARDO ABIB JR, PAULO LEAES, ROBERTO BOTELHO, OSCAR DUTRA, WEIMAR SOUZA, MARIA BRAILE, NILO IZUKAWA, JOSE CARLOS NICOLAU, LUIZ FERNANDO TANAJURA, CARLOS VICENTE SERRANO JUNIOR, CESAR MINELLI, LUIZ ANTONIO NASI, LIVIA OLIVEIRA, MARCELO JOSE DE CARVALHO CANTARELLI, RICHARD TYTUS, SHEKHAR PANDEY, EVA LONN, JAMES CHA, SAUL VIZEL, MOHAN BABAPULLE, ANDRE LAMY, KEVIN SAUNDERS, JOSEPH BERLINGIERI, BOB KIAII, RAKESH BHARGAVA, PRAVINSAGAR MEHTA, LAURIE HILL, DAVID FELL, ANDY LAM, FAISAL AL-QOOFI, CRAIG BROWN, ROBERT PETRELLA, JOSEPH A RICCI, ANTHONY GLANZ, NICOLAS NOISEUX, KEVIN BAINEY, FATIMA MERALI, MICHAEL HEFFERNAN, ANTHONY DELLA SIEGA, GILLES R DAGENAIS, FRANCOIS DAGENAIS, STEEVE BRULOTTE, MICHEL NGUYEN, MICHAEL HARTLEIB, RANDOLPH GUZMAN, RONALD BOURGEOIS, DENNIS RUPKA, YAARIV KHAYKIN, GILBERT GOSSELIN, THAO HUYNH, CLAUDE PILON, JEAN CAMPEAU, FRANCIS PICHETTE, ARIEL DIAZ, JAMES JOHNSTON, PRAVIN SHUKLE, GREGORY HIRSCH, PAUL RHEAULT, WLODZIMIERZ CZARNECKI, ANNIE ROY, SHAH NAWAZ, STEPHEN FREMES, DINKAR SHUKLA, GABRIEL JANO, JORGE LEONARDO COBOS, RAMON CORBALAN, MARCELO MEDINA, LEONARDO NAHUELPAN, CARLOS RAFFO, LUIS PEREZ, SERGIO POTTHOFF, BENJAMIN STOCKINS, PABLO SEPULVEDA, CHRISTIAN PINCETTI, MARGARITA VEJAR, HONGYAN TIAN, XUESI WU, YUANNAN KE, KAIYING JIA, PENGFEI YIN, ZHAOHUI WANG, LITIAN YU, SHULIN WU, ZONGQUI WU, SHAO WEN LIU, XIAO JUAN BAI, YANG ZHENG, PING YANG, YUN MEI YANG, JIWEI ZHANG, JUNBO GE, XIAO PING CHEN, JUNXIA LI, TAO HONG HU, RUIYAN ZHANG, ZHE ZHENG, XIN CHEN, LIANG TAO, JIANPING LI, WEIJIAN HUANG, GUOSHENG FU, CHUNJIAN LI, YUGANG DONG, CHUNSHENG WANG, XINMIN ZHOU, YE KONG, ARISTIDES SOTOMAYOR, JOSE LUIS ACCINI MENDOZA, HENRY CASTILLO, MIGUEL URINA, GUSTAVO AROCA, MARITZA PEREZ, DORA INES MOLINA DE SALAZAR, GREGORIO SANCHEZ VALLEJO, MANZUR J FERNANDO, HENRY GARCIA, LUIS HERNANDO GARCIA, EDGAR ARCOS, JUAN GOMEZ, FRANCISCO CUERVO MILLAN, FREDY ALBERTO TRUJILLO DADA, BORIS VESGA, GUSTAVO ADOLFO MORENO SILGADO, EVA ZIDKOVA, JEAN-CLAUDE LUBANDA, MARKETA KALETOVA, RADIM KRYZA, GABRIEL MARCINEK, MAREK RICHTER, JINDRICH SPINAR, JIRI MATUSKA, MARTIN TESAK, ZUZANA MOTOVSKA, MARIAN BRANNY, JIRI MALY, MARTIN MALY, MARTIN WIENDL, LENKA FOLTYNOVA CAISOVA, JOSEF SLABY, PETR VOJTISEK, JAN PIRK, LENKA SPINAROVA, MIROSLAVA BENESOVA, JULIA CANADYOVA, MIROSLAV HOMZA, JINDRICH FLORIAN, ROSTISLAV POLASEK, ZDENEK COUFAL, VLADIMIRA SKALNIKOVA, RADIM BRAT, MIROSLAV BRTKO, PETR JANSKY, JAROSLAV LINDNER, PAVEL MARCIAN, ZBYNEK STRAKA, MARTIN TRETINA, YAN CARLOS DUARTE, FREDDY POW CHON LONG, MAYRA SANCHEZ, JOSE LOPEZ, CARMITA PERUGACHI, RICARDO MARMOL, FREDDY TRUJILLO, PABLO TERAN, JAAKKO TUOMILEHTO, HENRI TUOMILEHTO, MARJA-LEENA TUOMINEN, ILKKA KANTOLA, GABRIEL STEG, VICTOR ABOYANS, FLORENCE LECLERCQ, EMILE FERRARI, FRANCK BOCCARA, EMMANUEL MESSAS, PATRICK MISMETTI, MARIE ANTOINETTE SEVESTRE, GUILLAUME CAYLA, PASCAL MOTREFF, STEFAN STOERK, HANS-DIRK DUENGEN, CHRISTOPH STELLBRINK, OSMAN GUEROCAK, CHRISTOPH KADEL, RUEDIGER BRAUN-DULLAEUS, MICHAEL JESERICH, CHRISTIAN OPITZ, HANS-FRIEDRICH VOEHRINGER, KARL-FRIEDRICH APPEL, BERNHARD WINKELMANN, THOMAS DORSEL, SIGRID NIKOL, HARALD DARIUS, JURGEN RANFT, SEBASTIAN SCHELLONG, WOLFGANG JUNGMAIR, PIROZE DAVIERWALA, MARC VORPAHL, LASZLO BAJNOK, ZOLTAN LASZLO, EBRAHIM NOORI, GABOR VERESS, ANDRAS VERTES, ANDRAS ZSARY, ERNO KIS, LASZLO KORANYI, JUDIT BAKAI, ZOLTAN BODA, FERENC POOR, ZOLTAN JARAI, VENDEL KEMENY, JOHN BARTON, BRENDAN MCADAM, ANDREW MURPHY, PETER CREAN, NIALL MAHON, RONAN CURTIN, BRIAIN MACNEILL, SEAN DINNEEN, MAJDI HALABI, REUVEN ZIMLICHMAN, DAVID ZELTSER, YOAV TURGEMAN, ELIEZER KLAINMAN, BASIL LEWIS, AMOS KATZ, SHAUL ATAR, EUGENIA NIKOLSKY, STEFANO BOSI, MONICA NALDI, POMPILIO FAGGIANO, DEBORA ROBBA, LUCIO MOS, GIANFRANCO SINAGRA, FRANCO COSMI, LUIGI OLTRONA VISCONTI, DE MATTEIS CARMINE, GIUSEPPE DI PASQUALE, MATTEO DI BIASE, SARA MANDORLA, MARINO BERNARDINANGELI, GIOVANNI CARLO PICCINNI, MICHELE MASSIMO GULIZIA, MARCELLO GALVANI, FLAVIO VENTURI, GIORGIO MOROCUTTI, MARIA GRAZIA BALDIN, CARLO OLIVIERI, GIAN PIERO PERNA, VINCENZO CIRRINCIONE, TAKAYASU KANNO, HIROYUKI DAIDA, YUKIO OZAKI, NAOMASA MIYAMOTO, SHINICHI HIGASHIUE, HIROSHI DOMAE, SHINOBU HOSOKAWA, HIROO KOBAYASHI, TAKEHIKO KURAMOCHI, KENSHI FUJII, KAZUAKI MIZUTOMI, KEIJIRO SAKU, KAZUO KIMURA, YOSHIHARU HIGUCHI, MITSUNORI ABE, HARUHITO OKUDA, TOSHIYUKI NODA, TERUAKI MITA, ATSUSHI HIRAYAMA, HARUHIKO ONAKA, MORIAKI INOKO, MITSUGU HIROKAMI, MUNENORI OKUBO, YUTAKA AKATSUKA, MIZUHO IMAMAKI, HARUO KAMIYA, MAMORU MANITA, TOSHIHARU HIMI, HIDEKI UENO, YUJI HISAMATSU, JUNYA AKO, YASUHIRO NISHINO, HIDEO KAWAKAMI, YUTAKA YAMADA, YUKIHIRO KORETSUNE, TAKAHISA YAMADA, TETSURO YOSHIDA, HIDEKI SHIMOMURA, NORIYUKI KINOSHITA, AKIHIKO TAKAHASHI, KHALID YUSOFF, WAN AZMAN WAN AHMAD, MUHAMMAD RADZI ABU HASSAN, SAZZLI KASIM, AIZAI AZAN ABDUL RAHIM, DIMON MOHD ZAMRIN, MASAHARU MACHIDA, YORIHIKO HIGASHINO, NORIAKI UTSU, AKIHIKO NAKANO, SHIGERU NAKAMURA, TETSUO HASHIMOTO, KENJI ANDO, TOMOHIRO SAKAMOTO, F.J. PRINS, DIRK LOK, JOHANNES GERT-JAN MILHOUS, ERIC VIERGEVER, FRANK WILLEMS, HENK SWART, MARCO ALINGS, ROB BREEDVELD, KEES-JAN DE VRIES, ROGER VAN DER BORGH, FANNY OEI, STIENEKE ZOET-NUGTEREN, HANS KRAGTEN, JEAN PAUL HERRMAN, PAUL VAN BERGEN, MARCEL GOSSELINK, EDUARD HOEKSTRA, ERWIN ZEGERS, EELKO RONNER, FRANK DEN HARTOG, GERARD BARTELS, PETER NIEROP, COEN VAN DER ZWAAN, JACOB VAN ECK, EDWIN VAN GORSELEN, BJORN GROENEMEIJER, PIETER HOOGSLAG, MARC ROBERT DE GROOT, ALDRIN LOYOLA, DENNIS JOSE SULIT, NANNETTE REY, MARIA TERESA ABOLA, DANTE MORALES, ELLEN PALOMARES, MARC EVANS ABAT, GREGORIO ROGELIO, PHILIP CHUA, JOSE CARLO DEL PILAR, JOHN DENNIS ALCARAZ, GERALDINE EBO, LOUIE TIRADOR, JOSEFINA CRUZ, JOHN ANONUEVO, ARTHUR PITARGUE, MARIANNA JANION, TOMASZ GUZIK, GRZEGORZ GAJOS, MACIEJ ZABOWKA, ANDRZEJ RYNKIEWICZ, MARLENA BRONCEL, ANDRZEJ SZUBA, DANUTA CZARNECKA, PAWEL MAGA, IRINA STRAZHESKO, YURY VASYUK, ZHANNA SIZOVA, YURY POZDNYAKOV, OLGA BARBARASH, MIKHAIL VOEVODA, TATIANA POPONINA, ALEXEY REPIN, IRINA OSIPOVA, ANNA EFREMUSHKINA, NINA NOVIKOVA, OLEG AVERKOV, DMITRY ZATEYSHCHIKOV, ARKADIY VERTKIN, AZA AUSHEVA, PATRICK COMMERFORD, SAADIYA SEEDAT, LOUIS VAN ZYL, JAN ENGELBRECHT, ELLEN MAKONLI MAKOTOKO, CATHARINA ELIZABETH PRETORIUS, ZAID MOHAMED, ADRIAN HORAK, THOMAS MABIN, ERIC KLUG, JANG-HO BAE, CHEOLHO KIM, CHONG-JIN KIM, DONG-SOO KIM, YONG JIN KIM, SEUNGJAE JOO, JONG-WON HA, CHUL SOO PARK, JANG YOUNG KIM, YOUNG-KWON KIM, CHRISTINA JARNERT, THOMAS MOOE, MIKAEL DELLBORG, INGEMAR TORSTENSSON, PER ALBERTSSON, LARS JOHANSSON, FARIS AL-KHALILI, HENRIK ALMROTH, TOMMY ANDERSSON, EMIL PANTEV, BENGT-OLOV TENGMARK, BO LIU, GUNDARS RASMANIS, CARL-MAGNUS WAHLGREN, TIZIANO MOCCETTI, ALEXANDER PARKHOMENKO, VIRA TSELUYKO, VOLODYMYR VOLKOV, OLENA KOVAL, LYUDMYLA KONONENKO, OLEKSANDR PROKHOROV, VALERIY VDOVYCHENKO, ANDRIY BAZYLEVYCH, LEONID RUDENKO, VADYM VIZIR, OLEKSANDR KARPENKO, YAROSLAV MALYNOVSKY, VALENTYNA KOVAL, BORYS STOROZHUK, JAMES COTTON, ASOK VENKATARAMAN, ANDREW MORIARTY, DEREK CONNOLLY, PATRICK DAVEY, ROXY SENIOR, INDERPAUL BIRDI, JOHN CALVERT, PATRICK DONNELLY, JASPER TREVELYAN, JUSTIN CARTER, AARON PEACE, DAVID AUSTIN, NEVILLE KUKREJA, THOMAS HILTON, SUNNY SRIVASTAVA, RONALD WALSH, RONALD FIELDS, JOSEPH HAKAS, EDWARD PORTNAY, HARINDER GOGIA, ABRAHAM SALACATA, JOHN J. HUNTER, J MICHAEL BACHARACH, NICOLAS SHAMMAS, DAMODHAR SURESH, RICKY SCHNEIDER, PAUL GURBEL, SUBHASH BANERJEE, PAUL GRENA, NOEL BEDWELL, STEPHEN SLOAN, STEVEN LUPOVITCH, ANAND SONI, KATHLEEN GIBSON, RENEE SANGRIGOLI, RAJENDRA MEHTA, PETER I-HSUAN TSAI, EVE GILLESPIE, STEPHEN DEMPSEY, GLENN HAMROFF, ROBERT BLACK, ELLIS LADER, JOHN B. KOSTIS, VERA BITTNER, WILLIAM MCGUINN, KELLEY BRANCH, VINAY MALHOTRA, STEPHEN MICHAELSON, MICHAEL VACANTE, MATTHEW MCCORMICK, RALUCA ARIMIE, ALAN CAMP, GEORGE DAGHER, N. MATHEW KOSHY, STEPHEN THEW, FREDERICK COSTELLO, MARK HEIMAN, ROBERT CHILTON, MICHAEL MORAN, FREDRIC ADLER, ANTHONY COMEROTA, ANDREW SEIWERT, WILLIAM FRENCH, HARVEY SEROTA, ROBERT HARRISON, FAISAL BAKAEEN, SHUAB OMER, LOKESH CHANDRA, ALAN WHELAN, ANDREW BOYLE, PHILIP ROBERTS-THOMSON, JAMES ROGERS, PATRICK CARROLL, DAVID COLQUHOUN, JAMES SHAW, PETER BLOMBERY, JOHN AMERENA, CHRIS HII, ALISTAIR ROYSE, BHUWAN SINGH, JOSEPH SELVANAYAGAM, SHIRLEY JANSEN, WINGCHI LO, CHRISTOPHER HAMMETT, ROHAN POULTER, SESHASAYEE NARASIMHAN, HENRIK WIGGERS, HENRIK NIELSEN, GUNNAR GISLASON, LARS KOBER, KIM HOULIND, VIBEKE BOENELYKKE SOERENSEN, ULRIK DIXEN, JENS REFSGAARD, ELISABETH ZEUTHEN, PETER SOEGAARD, MARIAN HRANAI, LUDOVIT GASPAR, DANIEL PELLA, KATARINA HATALOVA, ERIKA DROZDAKOVA, IOAN COMAN, DOINA DIMULESCU, DRAGOS VINEREANU, MIRCEA CINTEZA, CRINA SINESCU, CATALINA ARSENESCU, IMRE BENEDEK, ELENA BOBESCU, DAN DOBREANU, DAN GAITA, ADRIAN IANCU, ADRIANA ILIESIU, DANIEL LIGHEZAN, LUCIAN PETRESCU, OCTAVIAN PIRVU, IULIA TEODORESCU, DAN TESLOIANU, MARIUS MARCIAN VINTILA, and OVIDIU CHIONCEL

Subjects
Male, medicine.medical_treatment, Myocardial Infarction, Coronary Artery Disease, 030204 cardiovascular system & hematology, Stroke/epidemiology, Coronary artery disease, 0302 clinical medicine, Rivaroxaban, Hemorrhage/chemically induced, Carotid artery disease, 030212 general & internal medicine, Myocardial infarction, Cardiovascular Diseases/mortality, Aspirin, Atrial fibrillation, General Medicine, Stroke, ORAL RIVAROXABAN, Cardiovascular Diseases, Factor Xa Inhibitors/administration & dosage, Cardiology, Female, Drug Therapy, Combination, medicine.drug, medicine.medical_specialty, Rivaroxaban/administration & dosage, Coronary Artery Disease/drug therapy, Hemorrhage, Drug Administration Schedule, 03 medical and health sciences, Double-Blind Method, Internal medicine, Journal Article, Myocardial Infarction/epidemiology, medicine, Humans, Aspirin/administration & dosage, Platelet Aggregation Inhibitors/administration & dosage, Aged, Dose-Response Relationship, Drug, business.industry, Unstable angina, Percutaneous coronary intervention, medicine.disease, PREVENTION, Morbidity, business, Platelet Aggregation Inhibitors, Factor Xa Inhibitors
Abstract

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.

Published
2018

18. OPCAB surgery is cost-effective for elderly patients

Author

Kim, Houlind, Bo Juul, Kjeldsen, Susanne Nørgaard, Madsen, Bodil Steen, Rasmussen, Susanne Juel, Holme, Peter Appel, Pallesen, Poul Erik, Mortensen, Morten, Fenger-Grøn, Søren Jepsen, Beck, Lars Holger, Ehlers, and Jørgen, Lauridsen

Subjects
Male, medicine.medical_specialty, Time Factors, Cost-Benefit Analysis, Denmark, Coronary Artery Bypass, Off-Pump, Coronary Artery Disease, law.invention, Coronary artery disease, Indirect costs, Coronary artery bypass surgery, Postoperative Complications, Quality of life, Randomized controlled trial, law, Surveys and Questionnaires, medicine, Humans, Prospective Studies, Coronary Artery Bypass, Hospital Costs, Prospective cohort study, Aged, Aged, 80 and over, Chi-Square Distribution, business.industry, Age Factors, Perioperative, medicine.disease, Quality-adjusted life year, Surgery, Outcome and Process Assessment, Health Care, Treatment Outcome, Quality of Life, Female, Quality-Adjusted Life Years, Cardiology and Cardiovascular Medicine, business
Abstract

Objective. To determine the cost-effective operative strategy for coronary artery bypass surgery in patients above 70 years. Design. Randomized, controlled trial of 900 patients above 70 years of age subjected to coronary artery bypass surgery. Patients were randomized to either on-pump or off-pump coronary artery bypass surgery. Data on direct and indirect costs were prospectively collected. Preoperatively and six months postoperatively, quality of life was assessed using EuroQol-5D questionnaires. Perioperative in-hospital costs and costs of re-intervention were included. Results. The Summary Score of EuroQol-5D increased in both groups between preoperatively and postoperatively. In the on-pump group, it increased from 0.75 (0.16) (mean (SD)) to 0.84 (0.17), while the increase in the off-pump group was from 0.75 (0.15) to 0.84 (0.18). The difference between the groups was 0.0016 QALY and not significantly different. The mean costs were 148.940 D.Kr (CI, 130.623 D.Kr-167.252 D.Kr) for an on-pump patient and 138.693 D.Kr (CI, 123.167 D.Kr-154.220 D.Kr) for an off-pump patient. The ICER base-case point estimate was 6,829,999 D.Kr/QALY. The cost-effectiveness acceptability curve showed 89% probability of off-pump being cost-effective at a threshold value of 269,400 D.Kr/QALY. Conclusions. Off-pump surgery tends to be more cost-effective than on-pump surgery. Long-term comparisons are warranted.

Published
2013

19. Vein arterialization for lower limb revascularization

Author

Kim Houlind, Johnny Christensen, and Jepsen, Jørn M.

Subjects
Peripheral artery disease, Limb salvage, Vascular surgical procedures
Abstract

Conventional bypass surgery is only possible when patent distal arterial outflow vessels are available. In patients with critical limb ischemia and occluded distal arteries, attempts have been made to establish retrograde perfusion through either deep or superficial pedal veins. Though historical results were disappointing, more recently limb salvage has been achieved after adopting a principle of 1) placing the anastomosis distally, and 2) actively destroying the distal valves. Experimental, para-clinical, and clinical data confirm that direct tissue nutrition is improved, angiogenesis stimulated, and collaterals opened. Only a limited number of cases have been reported in the literature and a number of different operative techniques have been described. The results in terms of limb salvage and wound healing vary widely. Generally, results are poorer than what would have been expected if femoro-distal arterial bypass had been possible. Recently, hybrid approaches have been developed to avoid extensive distal incisions by endovascular destruction of valves and closure of side branches. Also, a totally endovascular technique, including the position of a stent graft between the vein and artery, has been proposed and tested. These developments may in the future improve results by limiting incisional wound complications and make this treatment available to more patients who would otherwise have no other alternative than amputation.

Published
2016

21. Vein arterialization for lower limb revascularization

Author

Kim, Houlind, Johnny K, Christensen, and Jørn M, Jepsen

Subjects
Femoral Artery, Lower Extremity, Humans, Arterial Occlusive Diseases, Vascular Surgical Procedures, Veins
Abstract

Conventional bypass surgery is only possible when patent distal arterial outflow vessels are available. In patients with critical limb ischemia and occluded distal arteries, attempts have been made to establish retrograde perfusion through either deep or superficial pedal veins. Though historical results were disappointing, more recently limb salvage has been achieved after adopting a principle of 1) placing the anastomosis distally, and 2) actively destroying the distal valves. Experimental, para-clinical, and clinical data confirm that direct tissue nutrition is improved, angiogenesis stimulated, and collaterals opened. Only a limited number of cases have been reported in the literature and a number of different operative techniques have been described. The results in terms of limb salvage and wound healing vary widely. Generally, results are poorer than what would have been expected if femoro-distal arterial bypass had been possible. Recently, hybrid approaches have been developed to avoid extensive distal incisions by endovascular destruction of valves and closure of side branches. Also, a totally endovascular technique, including the position of a stent graft between the vein and artery, has been proposed and tested. These developments may in the future improve results by limiting incisional wound complications and make this treatment available to more patients who would otherwise have no other alternative than amputation.

Published
2015

22. [Angiosome-directed revascularization of critical limb ischaemia]

Author

Kim, Houlind

Subjects
Lower Extremity, Ischemia, Regional Blood Flow, Angioplasty, Angiography, Humans, Vascular Grafting, Limb Salvage
Abstract

Critical limb ischaemia is the major cause of amputation in the developed world. When performing revascularization of the lower limb, guidelines recommend grafting of the "least diseased distal artery with the best continuous run-off to the ankle/foot... regardless of location" often implying indirect perfusion of the ischaemic area through collaterals. An alter-native strategy, called the "angiosome model", advocates a strategy which provides blood supply directly to the ischaemic area. This paper reviews the current evidence of indirect versus angiosome-directed revascularization of the lower limb.

Published
2015

28. Kombineret laser Doppler flowmetri og spectrophotometri som metode til vurdering af mikrocirculation

Author

Mette Berggren Olsen, Hanne Birke Sørensen, and Kim Houlind

Abstract

Kombineret laser Doppler flowmetri og spectrophotometri som metode til vurdering af mikrocirculation Berggren, MB, reservelæge, Karkirurgisk Afdeling, Kolding, mette.marie.berggren.olsen@slb.regionsyddanmark.dk; Houlind, K, lektor, afdelingslæge, Ph.d., Karkirurgisk afdeling, Kolding, kim.christian.houlind@slb.regionsyddanmark.dk; Sørensen, HB, lektor, speciallæge, Ph.d., Klinisk Institut, Århus Universitetshospital, hanne.Birke@ki.au.dk Foredragsholder: Berggren, MB, reservelæge, Karkirurgisk Afdeling, Kolding. Formål og baggrund: Postoperativ iskæmi er den største trussel mod autologe, mikrovaskulære transplantater. Da venøs occlusion er mere skadelig end arteriel, er det ønskeligt med en metode, som hurtigt og sikkert kan både afsløre og skelne mellem venøs og arteriel thrombose. O2C er en non-invasiv metode, som ved laser Doppler flowmetri og photospectroscopi måler flow, saturation, relativ hæmoglobin og flowhastighed i 2 og 8mm dybde. Tidligere in-vitro studier , indikerer, at metoden kan være et værdifuldt værktøj til monitorering af vævstransplantater, som giver mulighed for hurtigt at detektere vaskulære problemer, samt at skelne mellem venøs og arterielaflukning. Design: Deskriptivt, dyreeksperimentelt studie. Metoder: På 8 grise løftes højre og venstre rectusmuskel som fri lap og randomiseres til venøs eller arteriel okklusion. Der påsættes tang og på det relevante kar, og foretages O2C målinger hvert 5. min de første 30 min. og herefter hvert 15. min. Efter 3 timer fjernes tangen og der måles igen hvert 5. min. i 30 min. Data analyseres efterfølgende Vigtigste Variable: Ændringer i flow, hæmoglobin og saturation ved venøs og arteriel aflukning og reperfusion. Forventede resultater: Vi forventer at se, at en stigning i rHgb, samt et fald i flow og saturation i både 2 og 8mm dybde på lapperne med venøs obstruktion. På lapper med arteriel occlusion forventes et abrupt fald i flow og saturation. Såfremt ændringerne findes signifikante udregnes grænseværdier og SD.

Published
2012

29. Current Evidence of On-Pump Versus Off-Pump Coronary Artery By-Pass Surgery

Author

Kim Houlind

Subjects
System development, medicine.medical_specialty, Aorta, Beating heart, business.industry, medicine.medical_treatment, Disease, Anastomosis, Chest pain, Surgery, medicine.anatomical_structure, Internal medicine, medicine.artery, Cardiology, Medicine, Embolization, medicine.symptom, business, Artery
Abstract

Conventional coronary artery by-pass grafting (CCABG) performed using cardioplegic arrest and cardiopulmonary by-pass is a very well documented treatment for ischemic heart disease. The operation often relieves chest pain and it improves survival for patients with triplevessel disease and left main coronary artery disease. Since it was introduced in the late 1960 es, CCABG has become one of the most commonly performed operations. In 2007, an estimated 408.000 surgical coronary revascularizations were performed in the United States alone (1) Given the ageing populations in large parts of the world, CCABG is also increasingly being offered to elderly patients and to patients with co-morbidities. As a consequence, a significant number of operated patients suffer major or minor complications. Concerns have been raised that the use of cardiopulmonary by-pass (CPB) could cause neuro-cognitive dysfunction. Also, CPB has been linked to myocardial, renal and pulmonary damage. Several mechanisms have been suggested: Manipulation of the aorta during cannulation and clamping may cause dislodgment and embolization of atherosclerotic deposits, cardiac arrest may induce myocardial damage, and the long-lasting and repeated contact of blood with the non-biological surfaces of filters and tubing of the heartlungmachine induce mechanical wearing of the formed elements and biochemical over-activation of the immuneand coagulation systems Development of the Off-pump Coronary Artery By-pass (OPCAB) technique has been driven by concerns of these possible side-effects from CPB. On the other hand, concerns have been raised about whether the quality of anastomoses constructed “on the beating heart” i.e. without cardiopulmonary by-pass and cardioplegic arrest – would be as good as that of the anastomoses performed during CCABG. The question remains controversial. Best estimates of the proportion of surgical coronary revascularizations performed as OPCAB in the United States is around 25%. Some surgical centres perform almost all coronary by-pass operations off-pump, while others hardly or never use this technique. Tradition and economy dictate that OPCAB is the preferred method in some parts of the developing world. In the beginning of the OPCAB-experience, evidence was limited to small, published series by individual surgeons (2-3). Although seemingly providing good results, these observations were hampered by the lack of a control group. Later studies from databases were difficult to interpret because the original intention-to-treat was not

Published
2012

31. Coronary artery bypass surgery without the use of a heart-lung machine

Author

Kim Houlind, Bo Juel Kjeldsen, Terp, Kim A., Susanne Nørregaard Madsen, Schmidt, Thomas A., Susanne Juel Holme, and Poul Erik Mortensen

Abstract

Within recent years, off-pump coronary artery bypass (OPCAB) has gained renewed interest. Prospective, controlled, randomised trials comparing OPCAB with conventional coronary artery bypass using a heart-lung machine have documented a lower rate of minor complications such as postoperative bleeding, neurocognitive deficits, atrial fibrillation and infections. Furthermore, biochemical analyses show less myocardial and renal injury and less inflammatory reaction. Larger randomised trials are needed to determine the impact of OPCAB on perioperative death, stroke and myocardial infarction.

Published
2005

32. Thromboembolic complication following temporary discontinuance of anticoagulant therapy in a patient with mechanical heart valve

Author

Thomas Decker Christensen, Kim Houlind, Kaj Erik Klaaborg, Kure, Hans-Henrik O., Hans Eiskjaer, and John Michael Hasenkam

Subjects
Adult, Male, Coronary Thrombosis/chemically induced, Heart Valve Prosthesis, Heart Transplantation, Humans, Substance Withdrawal Syndrome/etiology, Anticoagulants/adverse effects, Warfarin/adverse effects, Aortic Valve Insufficiency/surgery, Thromboembolism/chemically induced
Abstract

Patients with mechanical heart valves are treated with oral anticoagulant therapy in order to minimize the risk of thromboembolism. During invasive procedures it is recommended to temporarily discontinue the oral anticoagulant therapy and substitute with injections of low-molecular-weight heparin. We describe a case where a patient discontinued the oral anticoagulant therapy and had no substitution with low-molecular-weight heparin. The patient had an embolism to the coronary arteries causing progressive heart failure, and the patient was subsequently heart transplanted.

Published
2003

37. Rehabilitering og palliation ved hjerte-kar-sygdom

Author

Ann Dorthe Olsen Zwisler, Vicky Joshi, Anne Merete Boas Soja, Vibeke Brogaard Hansen, Kim Houlind, Britt Borregaard, Mette Merlin Husted, Claus Engstrup, Amalie Martinus Hauge, Grete Brorholt, and Lars Hermann Tang

Abstract

An increasing number of Danes are living, and dying, with cardiovascular disease. There is good evidence for the impact of cardiac rehabilitation on coronary heart disease, heart failure and symptomatic peripheral arterial disease. However, more high-quality research is needed into a wider range of cardiac diseases including rehabilitation following cardiac arrest, and palliative care for patients with advanced heart disease. In this review it is discussed how to improve the quality of care and identify the direction of future research and development.

40. Left ventricular flow visualization by magnetic resonance velocity mapping

Author

Milet, Sylvain F., Walker, Peter G., Kim Houlind, Yong Kim, W., Erik Morre Pedersen, and Yoganathan, Ajit P.

Subjects
cardiovascular system
Abstract

Non-invasive three-dimensional cardiac flow velocity measurements was conducted on volunteer and patient groups using magnetic resonance (MR) velocity mapping technique. The data collected was visualized and analyzed using magnetic resonance imaging analyzer (MARIAN). Cardiac events were related to the flow pattern through the measurements of temporal flow velocity profiles at the mitral valve and one pulmonary vein. Significant differences were found between the patient and the volunteer groups in the temporal flow velocity profiles.

44. Intermittent claudication

Author

Christina Harlev, Kim Houlind, Janne Dyrby, and Amrit Rai

Abstract

Intermittent claudication is a manifestation of peripheral arterial occlusive disease. Multiple large international guidelines state that besides cardiovascular risk management, supervised exercise therapy (SET) should be offered to all patients with intermittent claudication. As described in this review, The Netherlands have already established a systemic rehabilitation program, ClaudicatioNet, where SET has been included and have shown positive outcomes. Despite all large national guidelines and the successful experience from the Netherlands, Denmark still fails to include SET to patients with intermittent claudication.

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