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Methane (CH4) emissions from natural landscapes constitute roughly half of global CH4 contributions to the atmosphere, yet large uncertainties remain in the absolute magnitude and the seasonality of emission quantities and drivers. Eddy covariance (EC) measurements of CH4 flux are ideal for constraining ecosystem-scale CH4 emissions due to quasi-continuous and high-temporal-resolution CH4 flux measurements, coincident carbon dioxide, water, and energy flux measurements, lack of ecosystem disturbance, and increased availability of datasets over the last decade. Here, we (1) describe the newly published dataset, FLUXNET-CH4 Version 1.0, the first open-source global dataset of CH4 EC measurements (available at https://fluxnet.org/data/fluxnet-ch4-community-product/, last access: 7 April 2021). FLUXNET-CH4 includes half-hourly and daily gap-filled and non-gap-filled aggregated CH4 fluxes and meteorological data from 79 sites globally: 42 freshwater wetlands, 6 brackish and saline wetlands, 7 formerly drained ecosystems, 7 rice paddy sites, 2 lakes, and 15 uplands. Then, we (2) evaluate FLUXNET-CH4 representativeness for freshwater wetland coverage globally because the majority of sites in FLUXNET-CH4 Version 1.0 are freshwater wetlands which are a substantial source of total atmospheric CH4 emissions; and (3) we provide the first global estimates of the seasonal variability and seasonality predictors of freshwater wetland CH4 fluxes. Our representativeness analysis suggests that the freshwater wetland sites in the dataset cover global wetland bioclimatic attributes (encompassing energy, moisture, and vegetation-related parameters) in arctic, boreal, and temperate regions but only sparsely cover humid tropical regions. Seasonality metrics of wetland CH4 emissions vary considerably across latitudinal bands. In freshwater wetlands (except those between 20g g€¯S to 20g g€¯N) the spring onset of elevated CH4 emissions starts 3g€¯d earlier, and the CH4 emission season lasts 4g€¯d longer, for each degree Celsius increase in mean annual air temperature. On average, the spring onset of increasing CH4 emissions lags behind soil warming by 1 month, with very few sites experiencing increased CH4 emissions prior to the onset of soil warming. In contrast, roughly half of these sites experience the spring onset of rising CH4 emissions prior to the spring increase in gross primary productivity (GPP). The timing of peak summer CH4 emissions does not correlate with the timing for either peak summer temperature or peak GPP. Our results provide seasonality parameters for CH4 modeling and highlight seasonality metrics that cannot be predicted by temperature or GPP (i.e., seasonality of CH4 peak). FLUXNET-CH4 is a powerful new resource for diagnosing and understanding the role of terrestrial ecosystems and climate drivers in the global CH4 cycle, and future additions of sites in tropical ecosystems and site years of data collection will provide added value to this database. All seasonality parameters are available at 10.5281/zenodo.4672601 (Delwiche et al., 2021). Additionally, raw FLUXNET-CH4 data used to extract seasonality parameters can be downloaded from https://fluxnet.org/data/fluxnet-ch4-community-product/ (last access: 7 April 2021), and a complete list of the 79 individual site data DOIs is provided in Table 2 of this paper.

The Body-Mind-Spirit model of health promotion (Chan, Ho&Chow, 2002) guided the construction of a multidimensional inventory for assessing holistic health. Named Body-Mind-Spirit Well-Being Inventory (BMSWBI), it comprises four scales: Physical Distress, Daily Functioning, Affect, and Spirituality (differentiated from religiosity and conceived as ecumenical). Respondents (674 Chinese adults from Hong Kong) completed the BMSWBI via the Internet. Results indicate that all four scales have high reliability, with alpha coefficients ranging from .87 to .92, and concurrent validity. Factor analysis indicates that (a) positive and negative affect form two distinct factors; and (b) spirituality comprises three distinct aspects, tranquility, resistance to disorientation, and resilience. Spirituality is positively associated with mental well-being, positive affect, satisfaction with life, and hope; but negatively associated with negative affect and perceived stress. These results suggest that the inventory may be used to assess different dimensions of health satisfactorily. [ABSTRACT FROM AUTHOR]

The effects of clobazam on critical flicker fusion threshold (CEFT) and menstrual cycle-related symptomatology were examined in a double-blind placebo-controlled study of 11 normally cycling women. Clobazam 10 mg or placebo was administered in two doses, the evening before and the morning of testing at four points in the menstrual cycle (days 7, 14. 21 and 26). Subjects were tested on CEFT and completed the Menstrual Distress Questionnaire (MDQ) and the Premenstrual Mood Index (PMI). Results showed that clobazam did not disrupt the menstrual cycle rhythm in CFFT. which accords with the non-sedative nature of this drug. The lack of effect of clobazam on subjective indices. Impaired Concentration and Behaviour Change of the MDQ confirms the tack of sedative effects, A general tendency. however, was observed For clobazam to reduce symptom reports on some other MDQ PMI scales in the first half of the cycle and to produce a subsequent exacerbation of symptoms in the second half of the cycle. [ABSTRACT FROM AUTHOR]

Importance: Perioperative bleeding is a major concern in patients receiving ticagrelor for acute coronary syndromes (ACS) when coronary artery bypass graft (CABG) surgery is required., Objective: To evaluate whether early CABG surgery at 2 to 3 days after ticagrelor cessation is noninferior to waiting 5 to 7 days., Design, Setting, and Participants: RAPID CABG was a noninferiority, open-label randomized trial with 6 months of follow-up. Participants were patients with ACS who had received ticagrelor and required CABG. Patients were enrolled in tertiary centers in Canada between January 2016 and March 2021. Data were analyzed from March 2021 to December 2023., Intervention: Early or delayed CABG., Main Outcomes and Measures: The primary outcome was based on noninferiority comparison of class 3 or 4 universal definition of perioperative bleeding (UDPB). Noninferiority was prespecified as 8% between groups. Twelve-hour chest tube drainage was reported as a noninferiority comparison. Other bleeding, ischemic, and length-of-stay outcomes were assessed for superiority., Results: Among 143 randomized patients, the median (IQR) age was 65 (58-72) years; there were 117 male patients (82%) and 26 female (18%). Of these, 123 patients (86.0%) underwent surgery in the allocated time frame (per protocol). The median (IQR) time to surgery was 3 (2-3) days in the early group and 6 (5-7) days in the delayed group (P < .001). In a per-protocol analysis, severe or massive UDPB occurred in 3 of 65 early-group patients (4.6%) and 3 of 58 patients (5.2%) in the delayed group (between-group difference, -0.6%; 95% CI, -8.3% to 7.1%; P = .03 for noninferiority). Median (IQR) chest tube drainage was 470 (330-650) mL vs 495 (380-610) mL (between-group difference -25 mL; 95% CI, -111.25 to 35; P = .01 for noninferiority). Median (IQR) hospital stay was 9 (7-13) days and 12 (10-15) days for the early and delayed groups (P < .001)., Conclusion and Relevance: This study found that an early surgical strategy, 2 to 3 days after ticagrelor cessation, was noninferior in incurring perioperative bleeding. The data support a reduction in the delay between ticagrelor cessation and CABG surgery and may decrease hospital length of stay., Trial Registration: ClinicalTrials.gov Identifier: NCT02668562.

Current evidence indicates that dual antiplatelet therapy with aspirin plus a P2Y 12 inhibitor is essential for the prevention of thrombotic events after percutaneous coronary interventions. However, dual antiplatelet therapy is associated with increased bleeding which may outweigh the benefits. This has set the foundations for customizing antiplatelet treatments to the individual patient. However, bleeding and ischemic risks are often present in the same patient, making it difficult to achieve this balance. The fact that oral P2Y 12 inhibitors (clopidogrel, prasugrel, and ticagrelor) have diverse pharmacodynamic profiles that affect clinical outcomes supports the rationale for using platelet function and genetic testing to individualize antiplatelet treatment regimens. Indeed, up to one-third of patients treated with clopidogrel, but a minority of those treated with prasugrel or ticagrelor, exhibit high residual platelet reactivity resulting in an increased thrombotic risk. On the other hand, prasugrel and ticagrelor are frequently associated with low platelet reactivity and increased bleeding risk compared with clopidogrel without providing any additional reduction in ischemic events compared with patients who adequately respond to clopidogrel. The use of platelet function and genetic testing may allow for a guided selection of oral P2Y 12 inhibitors. However, the nonuniform results of randomized controlled trials have led guidelines to provide limited recommendations on the implementation of these tests in patients undergoing percutaneous coronary intervention. In light of recent advancements in the field, this consensus document by a panel of international experts fills in the guideline gap by providing updates on the latest evidence in the field as well as recommendations for clinical practice., Competing Interests: Funding Support and Author Disclosures Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly, Faraday, Haemonetics, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Faraday, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr Alexopoulos has received advisory board fees or honoraria from AstraZeneca, Bayer, Chiesi, and Pfizer; and institutional research grants from CSL Behring. Dr Aradi has received lecture fees from Amgen, AstraZeneca, Bayer AG, Biotronik, Boehringer, Egis, Krka, Medtronic, Novartis, Novo Nordisk, Pfizer, Richter Gedeon, and Vascular Venture. Dr Bhatt has served on the advisory board for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; has served on the Board of Directors for American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); has served as a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; has served on Data Monitoring Committees for Acesion Pharma, Assistance Publique–Hôpitaux de Paris, the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic, the Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, the Population Health Research Institute, Rutgers University (for the National Institutes of Health–funded MINT trial); has served as a Data Monitoring Committee chair for Boston Scientific (PEITHO trial) and Contego Medical (PERFORMANCE 2); has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), the Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Cowen and Company, the Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), JACC (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (continuing medical education steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and U.S. national co-leader, funded by Bayer), WebMD (continuing medical education steering committees), and Wiley (steering committee); has served as the Deputy Editor for Clinical Cardiology; owns a patent for Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither Dr Bhatt nor Brigham and Women's Hospital receives any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); has served as a Site Co-Investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; has been a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo. Dr Bonello’s his institution received payment from INARI, Boston Scientific, Abbott, Biotronik, and Bristol Myers Squibb. Dr Capodanno has received payment as an individual for consulting fees or honoraria from Sanofi. Dr Cavallari has received research support from Werfen. Dr Cuisset has received consulting and lecture fees from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Europa Organisation, Medtronic, Terumo, and Sanofi. Dr Ferreiro has received lecture honoraria from Eli Lilly, Daiichi-Sankyo, AstraZeneca, Pfizer, Abbott, Boehringer Ingelheim, Bristol Myers Squibb, Rovi, Terumo and Ferrer; consulting fees from AstraZeneca, Eli Lilly, Ferrer, Boston Scientific, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Bristol Myers Squibb, and Biotronik; and research grants from AstraZeneca. Dr Franchi has received payment as an individual for consulting fees or honoraria from AstraZeneca; and institutional payments for grants from PLx Pharma and the Scott R. MacKenzie Foundation. Dr Geisler has received lecture honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Ferrer/Chiesi, Novartis, and Pfizer; consulting fees from AstraZeneca, Bristol Myers Squibb, Ferrer, Edwards Lifesciences, Haemonetics, and Pfizer; and research grants from Bayer, Bristol Myers Squibb/Pfizer, Ferrer/Chiesi, Medtronic, and Edwards Lifesciences. Dr Gibson has received grants from SCAD Alliance, Johnson & Johnson, Janssen, and CSL Behring; has received personal fees from Bayer, AstraZeneca (during the conduct of the study), Angel Medical Corporation, CSL Behring, Janssen, Johnson & Johnson, the Boston Clinical Research Institute, the Cardiovascular Research Foundation, Gilead Sciences, WebMD, UpToDate in Cardiovascular Medicine, Somahlution, Boston Scientific, the Duke Clinical Research Institute, Medtelligence, Microport, PERT Consortium, Caladrius Biosciences, CeleCor Therapeutics, Eidos Therapeutics, Microdrop, MD Magazine, the Society for Cardiovascular Angiography and Interventions, Revance Therapeutics, Pfizer, Dyad Medical, CytoSorbents, AMAG Pharmaceuticals, Bristol Myers Squibb, Amarin, PhaseBio, Bioclinica, Inari, MedImmune, PLx Pharma, Merck, Paratek, Anthos Therapeutics, PHRI, SmartMedics, EXCITE International ($0 received), Novo Nordisk, MedTrace, and the Cardiovascular Clinical Science Foundation; has received nonfinancial support from the Baim Institute; and owns equity in nference, Absolutys, and Dyad Medical. Dr Gorog has received institutional research grants from Bayer, AstraZeneca, Medtronic, and Werfen; and personal fees from Janssen, Bristol Myers Squibb, and Chiesi. Dr Gurbel has received consulting fees and/or honoraria from Bayer, Vectura/Otitopic, Janssen, Cleveland Clinic Foundation, Wolters Kluwer Pharma, Web MD Medscape, Baron and Budd, Premier Health Care Resource, Baim Institute, and Medforce; has received institutional research grants from Accriva Diagnostics, AstraZeneca, Bayer, Cronos, Janssen Pharmaceuticals Inc., Haemonetics, Hikari Dx, Idorisa, Labcorp Drug Development, Novartis, Prolocor, Recor Medical, Vectura Limited, and Zoll Medical Corporation; owns 2 patents (Detection of restenosis risk in patients issued and Assessment of cardiac health and thrombotic risk in a patient); has served as an expert witness in a lawsuit associated with Plavix. Dr Jeong has received honoraria for lectures from Daiichi-Sankyo, Sanofi, Han-mi Pharmaceuticals, and Daewoong Pharmaceuticals; and research grants or support from Samjin Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals, Biotronik Korea, and U and I Corporation. Dr Marcucci has received consulting fees or honoraria from Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Novartis, Sanofi, Viatris, and Werfen. Dr Siller-Matula has received speaker or consulting fees from AOP, Chiesi, Biosensors, Boston Scientific, P&F, Boehringer Ingelheim, and Daiichi-Sankyo not related to the submitted work. Dr Mehran has received institutional research payments from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi-Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, Shockwave, Vivasure, and Zoll; has received personal fees from Cine-Med Research and WebMD; owns equity (<1%) in Applied Therapeutics, Elixir Medical, Stel, and ControlRad (via her spouse); has served on the Scientific Advisory Board for the American Medical Association, the American College of Cardiology (Board of Trustees Member), the Society for Cardiovascular Angiography and Interventions (Women in Innovations Committee Member), and JAMA (Associate Editor); and has served as faculty for the Cardiovascular Research Foundation (no fee). Dr Neumann has received consulting honoraria from Novartis and Meril; speaker honoraria from Boston Scientific, Amgen, Daiichi-Sankyo, and Meril; speaker honoraria paid to his institution from Bristol Myers Squibb/Pfizer, Daiichi-Sankyo, Boston Scientific, Siemens, and Amgen; and research grants paid to his institution from Boston Scientific and Abbott. Dr So has received consulting fees or honoraria from Abbott Vascular, AstraZeneca, Bayer, HLS Therapeutics, JAMP Pharma Corp, Medtronic, and DYFS; and received research grants from Aggredyne, Diapharma, Eli Lilly, Fujimori Kogyo, Roche Diagnostics, and Spartan Biosciences. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; served as a consultant for Abbott, Daiichi-Sankyo, Ablative Solutions, CorFlow, Cardiomech, Robocath, Miracor, Vectorious, Abiomed, Valfix, Apollo Therapeutics, Elucid Bio, Cardiac Success, TherOx, HeartFlow, Neovasc, Ancora, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, HighLife, Elixir, Remote Cardiac Enablement, and Aria; he owns equity/options in Cardiac Success, Ancora, Cagent, Applied Therapeutics, and Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Valfix, and Xenter; and his employer (Mount Sinai Hospital) has received research grants from Shockwave, Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense Webster, Vascular Dynamics, Pulnovo, and V-wave. Dr Storey has received institutional research grants/support from AstraZeneca and Cytosorbents; and personal fees from Alfasigma, AstraZeneca, Boehringer Ingelheim/Lilly, Chiesi, Cytosorbents, Daiichi-Sankyo, Idorsia, Novartis, Novo Nordisk, Pfizer, PhaseBio, and Tabuk. Dr Tantry has received honoraria from Wolters Kluwer Pharma. Dr ten Berg has received institutional research grants from ZonMw (Dutch Government) and Daiichi-Sankyo; has served on the advisory board CeleCor; and has received lecture and advisory board fees paid to his institution from AstraZeneca, Bristol Myers Squibb, and Pfizer. Dr Trenk has received honoraria for lectures from AstraZeneca, Daiichi-Sankyo, and Novartis; and consulting fees from Atriva, Daiichi-Sankyo, and Eleva. Dr Valgimigli has received personal fees from AstraZeneca, Terumo, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals Ltd, Universität Basel | Dept. Klinische Forschung, Bristol Myers Squibb SA/Janssen, Medscape, Biotronik, Novartis, and Vesalio, outside the submitted work; and grants from Terumo, outside the submitted work. Dr Waksman has served on advisory boards for Abbott Vascular, Boston Scientific, J Valve, Medtronic Inc, Philips IGT, and Pi-Cardia Ltd.; has served as a consultant for Abbott Vascular, Biotronik, Boston Scientific, CardioMed LLC, Cordis, Medtronic Inc, Philips IGT, Pi-Cardia Ltd., Swiss Interventional Systems/SIS Medical AG, Transmural Systems Inc., and Venous MedTech; has received institutional grant support from Amgen, Biotronik, Boston Scientific, Chiesi, Medtronic Inc, and Philips IGT; and is an investor in MedAlliance, Pi-Cardia Ltd., and Transmural Systems. Dr Sibbing has received speaker fees and fees for advisory board activities from Bayer, Sanofi, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Canada is the only country with universal health care lacking universal pharmaceutical care (pharmacare). Currently, a minority portion of the population has drug coverage. Furthermore, there may be discordance between provincial plans of medications that are covered. We aimed to evaluate present systems for drug coverage and ability to provide evidence-based care according to Canadian cardiovascular (CV) guidelines., Methods: The drug review process and formularies for provinces and territories were queried to evaluate concordance between guideline-recommended medications and present coverage. Two common cardiology scenarios, heart failure with reduced ejection fraction and antiplatelet drugs in acute coronary syndrome, were chosen as case studies because of recent Canadian-based CV practice guideline updates. Coverage criteria were extracted to assess for interprovincial variations and determine whether listing decisions are concordant with best evidence and guidelines., Results: Multiple organisations are involved in drug review. Despite Canada's Drug and Health Technology Agency (CADTH) recommendations, there are extensive interprovincial variations in listing decisions for CV drugs, with CADTH recommendations followed only 33% of the time. Among 24 CV drugs reviewed, 23% of listing decisions were discordant from guidelines and best evidence. Novel drugs disproportionately carried the highest discordance from evidence. No systematic process exists for formulary updates based on new evidence, changes in guidelines, or drug pricing., Conclusions: Current Canadian drug review decisions are complex and coverage decisions vary widely, resulting in an inability to provide guideline-recommended CV evidence-based medicine. In developing future pharmacare programs, it is crucial to centralise the drug review process and integrate mechanisms to incorporate up-to-date evidence., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background: Wide interhospital variations exist in cardiovascular intensive care unit (CICU) admission practices and the use of critical care restricted therapies (CCRx), but little is known about the differences in patient acuity, CCRx utilization, and the associated outcomes within tertiary centers., Methods: The Critical Care Cardiology Trials Network is a multicenter registry of tertiary and academic CICUs in the United States and Canada that captured consecutive admissions in 2-month periods between 2017 and 2022. This analysis included 17 843 admissions across 34 sites and compared interhospital tertiles of CCRx (eg, mechanical ventilation, mechanical circulatory support, continuous renal replacement therapy) utilization and its adjusted association with in-hospital survival using logistic regression. The Pratt index was used to quantify patient-related and institutional factors associated with CCRx variability., Results: The median age of the study population was 66 (56-77) years and 37% were female. CCRx was provided to 62.2% (interhospital range of 21.3%-87.1%) of CICU patients. Admissions to CICUs with the highest tertile of CCRx utilization had a greater burden of comorbidities, had more diagnoses of ST-elevation myocardial infarction, cardiac arrest, or cardiogenic shock, and had higher Sequential Organ Failure Assessment scores. The unadjusted in-hospital mortality (median, 12.7%) was 9.6%, 11.1%, and 18.7% in low, intermediate, and high CCRx tertiles, respectively. No clinically meaningful differences in adjusted mortality were observed across tertiles when admissions were stratified by the provision of CCRx. Baseline patient-level variables and institutional differences accounted for 80% and 5.3% of the observed CCRx variability, respectively., Conclusions: In a large registry of tertiary and academic CICUs, there was a >4-fold interhospital variation in the provision of CCRx that was primarily driven by differences in patient acuity compared with institutional differences. No differences were observed in adjusted mortality between low, intermediate, and high CCRx utilization sites., Competing Interests: Disclosures Dr Barnett reports clinical trial enrollment for Acceleron, Merck, Merck Shape & Dohme, and Aerovate Therapeutics. Dr Bohula, Dr Morrow, and J. Guo are members of the TIMI study group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc, Daiichi Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc, Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Roche, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, The Medicines Company, and Zora Biosciences. Dr Morrow has received consulting fees from Abbott Laboratories, ARCA Biopharma, InCarda, Inflammatix, Merck, Novartis, and Roche Diagnostics. Dr Daniels reports consulting income from Roche Diagnostics and QuidelOrtho serves on clinical end point adjudication committees for Abbottand Applied Therapeutics. Dr Prasad reports advisory board for Abiomed and NIH R01 grant. Dr Teuteberg reports consulting with Abbott, Abiomed advisory board, CareDx advisory board and speaking fees, Cytokinetics speaking fees, Medtronic advisory board, speaking and consulting fees, Paragonix speaking fees, and Takeda advisory board. The other authors report no conflicts.

Loss-of-function CYP2C19 variants are associated with increased cumulative ischemic outcomes warranting CYP2C19 genotyping prior to clopidogrel administration. TAILOR-PCI was an international, multicenter (40 sites), prospective, randomized trial comparing rapid point of care (POC) genotype-guided vs. conventional anti-platelet therapy. The performance of buccal-based rapid CYP2C19 genotyping performed by non-laboratory-trained staff in TAILOR-PCI was assessed. Pre-trial training and evaluation involved rapid genotyping of 373 oral samples, with 99.5% (371/373) concordance with Sanger sequencing. During TAILOR-PCI, 5302 patients undergoing PCI were randomized to POC rapid CYP2C19 *2, *3, and *17 genotyping versus no genotyping. At 12 months post-PCI, TaqMan genotyping determined 99.1% (2,364/2,385) concordance with the POC results, with 90.7-98.8% sensitivity and 99.2-99.6% specificity. In conclusion, non-laboratory personnel can be successfully trained for on-site instrument operation and POC rapid genotyping with analytical accuracy and precision across multiple international centers, thereby supporting POC genotyping in patient-care settings, such as the cardiac catheterization laboratory.Clinical Trial Registration: https://www.clinicalTrials.gov (Identifier: NCT01742117)., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims: The PRECISE-DAPT (Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) score identifies patients at high risk of bleeding complications following percutaneous coronary intervention (PCI). International guidelines recommend the PRECISE-DAPT score to identify patients at high risk for bleeding, who may benefit from shortened dual antiplatelet therapy. The association of the PRECISE-DAPT score with ischaemic outcomes remains unclear. We performed a meta-analysis investigating the association between a high PRECISE-DAPT score and ischaemic outcomes., Methods and Results: A comprehensive literature search was conducted on articles published between 11 March 2017 and 5 June 2021. Two reviewers independently screened articles for inclusion using pre-defined criteria. The outcome measures extracted included composite ischaemic events, major bleeding events, and all-cause mortality. A random effects model was applied to obtain combined risk estimates for outcomes. From 12 included studies, there were 39 459 patients with PRECISE-DAPT <25 and 14 761 patients with PRECISE-DAPT ≥25. PRECISE-DAPT score ≥25 was associated with increased risk of composite ischaemic events [odds ratio (OR) 2.16; 95% confidence interval (CI) 1.77-2.65], myocardial infarction (OR 2.06; 95% CI 1.38-3.08), and ischaemic stroke (OR 2.90; 95% CI 1.76-4.78). Patients with a PRECISE-DAPT score ≥25 had increased risk of major bleeding (OR 3.62; 95% CI 2.62-4.99). Patients with a PRECISE-DAPT score ≥25 had higher risk of all-cause mortality (OR 5.83; 95% CI 5.37-6.33)., Conclusion: Patients with a PRECISE-DAPT score ≥25 are at increased risk for ischaemic events, bleeding, and all-cause mortality. Prospective evaluation of a PRECISE-DAPT guided approach to antiplatelet therapy is required to demonstrate benefit in this high-risk population., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to decreased Clopidogrel Response After Percutaneous Coronary Intervention) studied genotype-guided selection of antiplatelet therapy after percutaneous coronary intervention versus conventional therapy with clopidogrel. The presence of CYP2C19 loss-of-function alleles in patients treated with clopidogrel may be associated with increased risk for ischemic events. We report a prespecified sex-specific analysis of genotyping and associated cardiovascular outcomes from this study. Methods and Results Associations between sex and major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia) and Bleeding Academic Research Consortium (BARC) bleeding at 12 months were analyzed using Cox proportional-hazards models. Among 5276 randomized patients, loss-of-function carriers were observed in ≈36% of both sexes, and >80% of carriers were heterozygotes. At 12 months, after adjustment for baseline differences, risks of MACE (HR , 1.28 [0.97 to 1.68]; P =0.088) and BARC bleeding (hazard ratio [HR], 1.36 [0.91 to 2.05]; P =0.14) were comparable among women and men. There were no significant interactions between sex and treatment strategy for MACE interaction P value ( P int =0.59) or BARC bleeding ( P int =0.47) nor for sex and genotype (MACE P int =0.15, and BARC bleeding P int =0.60). Conclusions CYP2C19 loss-of-function alleles were present in ≈1 in 3 women and men. Women had similar adjusted risks of MACE and bleeding as men following percutaneous coronary intervention. Genotype-guided therapy did not significantly reduce the risk of MACE or bleeding relative to conventional therapy for both sexes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01742117.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is prescribed for 1-year after myocardial infarction. Two clinical strategies are considered at 1-year: continuation of DAPT or "Dual Pathway" (DP), using aspirin and rivaroxaban. No head-to-head comparative studies exist. In our in-vitro study, 24 samples of donor blood were treated with clinically proven concentrations of 5 antithrombotic regimens: aspirin, ticagrelor, rivaroxaban, DAPT, and DP. Thrombosis was analyzed using the Total Thrombus Analysis System (T-TAS) to measure both antiplatelet and anticoagulant effects. Flow cytometry was performed to quantify platelet activation. DAPT was the most potent antiplatelet regimen, delaying thrombus onset ( p < .0001) and reducing thrombogenicity ( p < .0001), relative to control. DP did not delay thrombus formation relative to aspirin alone ( p = .69). DP was the most potent anticoagulant regimen, delaying thrombus onset ( p < .0001) and reducing thrombogenicity ( p < .0001), relative to control. DP showed synergistic antithrombotic effects by delaying thrombus onset ( p < .0001) and reducing thrombogenicity ( p = .0003), relative to rivaroxaban alone. Flow cytometry showed only DAPT ( p = .0023) reduced platelet activation. DP treatment demonstrated synergistic antithrombotic effects over rivaroxaban alone, but no additional antiplatelet synergism over aspirin alone.

The optimal length of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remains debated. Current guidelines recommend individualized treatment with consideration of risk scores. We sought to evaluate the degree of agreement in treatment recommendations and the ability to predict ischemic and bleeding complications of the PRECISE-DAPT (predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy) and DAPT scores. Consecutive patients receiving 12 months of DAPT were grouped based on score treatment recommendation at the time of PCI: PRECISE-DAPT prolonged or shortened (PRECISE DAPT <25 vs ≥25) and DAPT prolonged or shortened (DAPT ≥2 vs <2). One-year ischemic and bleeding outcomes were compared for each group. In 451 patients, the PRECISE-DAPT and DAPT score recommendations were concordant in 56.7% of patients (Cohen's kappa for agreement of k = 0.139, 95% confidence interval 0.065 to 0.212). There was no difference in composite major adverse cardiovascular and cerebrovascular events between patients with high versus low PRECISE-DAPT or DAPT scores. In patients with a high PRECISE-DAPT score versus a low score, there was an increased incidence of 1-year all-cause mortality (2.13% vs 0%, p = 0.04) and an increase in bleeding (Bleeding Academic Research Consortium ≥3a: 17.0% vs 2.8%; p <0.001; Bleeding Academic Research Consortium 3b/c and 5: 8.5% vs 1.4%; p = 0.001). There were no differences in rates of mortality or bleeding for patients with high versus low DAPT scores. In conclusion, when applied at the baseline, the PRECISE-DAPT and DAPT scores frequently make discordant DAPT duration recommendations. The PRECISE-DAPT, but not the DAPT score, demonstrated associations with all-cause mortality and bleeding in patients prescribed 12 months of DAPT after PCI., Competing Interests: Disclosures Dr. So (principal investigator) reports receiving unrestricted grant supports from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, National Institutes of Health, Eli-Lilly Canada Inc, Spartan Bioscience, Roche Diagnostics, and Aggredyne; and speaker honoraria and advisory board honoraria from AstraZeneca Pharmaceuticals LP and Bayer Canada. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A better understanding of the central role of inflammation in the development of coronary artery disease (CAD) has been the impetus for the evaluation of therapeutic strategies targeting the interleukin-1ß/interleukin-6 cytokine signaling pathway, involved in both chronic atherogenesis and in triggering of atherosclerotic plaque rupture. As an inexpensive pharmacologic agent with relatively few adverse effects that tend to be mild and tolerable, the role of colchicine in secondary prevention of atherothrombotic events has been the focus of multiple recent large-scale randomized controlled trials involving patients with stable CAD (Low-Dose Colchicine [LoDoCo] and LoDoCo2 trials), a recent myocardial infarction (Colchicine Cardiovascular Outcome Trial [COLCOT], Colchicine in Patients With Acute Coronary Syndrome [COPS], and Colchicine and Spironolactone in Patients With Myocardial Infarction/Synergy Stent Registry [CLEAR SYNERGY] trials), and undergoing percutaneous coronary interventions (Colchicine in Percutaneous Coronary Intervention [COLCHICINE-PCI] trial). Based on this evidence, low-dose colchicine (0.5 mg once daily) should be considered in patients with recent myocardial infarctions-within 30 days and, ideally, within 3 days-or with stable CAD to improve cardiovascular outcomes. Colchicine should not be used in patients with severe renal or hepatic disease because of the risk of severe toxicity. No serious adverse effect was associated with the combined use of colchicine and high-intensity statin therapy in large trials. The impact of colchicine in high-risk populations of patients with peripheral arterial disease and in those with diabetes for the primary prevention of CAD remains to be established., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: In patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), selecting an antithrombotic regimen requires balancing risks of ischemic cardiac events, stroke, and bleeding., Methods: We studied 467 patients with AF undergoing PCI in the time period from December 2015 to July 2018 identified via a chart audit by 47 Canadian cardiologists in the CONNECT AF+PCI (the Co ordinated N ational N etwork to E ngage Interventional C ardiologists in the Antithrombotic T reatment of Patients With A trial F ibrillation Undergoing P ercutaneous C oronary I ntervention) study, to determine patterns of initial antithrombotic therapy selection., Results: The median (25th, 75th percentile) CHADS 2 score was 2 (1, 3), and PCI was performed in the setting of acute coronary syndrome in 62.1%. Triple antithrombotic therapy (TAT) was the initial treatment in 62.7%, dual-pathway therapy in 25.7%, and dual antiplatelet therapy in 11.6%, with a temporal increase in use of dual-pathway therapy during the course of the study; median intended TAT duration was 1 (1, 3) month. Compared with patients selected for TAT, patients selected for dual-pathway therapy were less likely to have prior myocardial infarction (35.8% vs 25.8%, P  = 0.045) and prior PCI (33.8% vs 23.3%, P  = 0.03), and they received shorter total length of stents (38 [23, 56] vs 30 [20, 46] mm, P  = 0.03). Patients selected for dual-pathway therapy had a higher prevalence of prior stroke/transient ischemic attack (13.0% vs 23.3%, P  = 0.01). There was no difference in prevalence of anemia (21.5% vs 25.8%, P  = 0.30). Use of dual-pathway therapy was similar among patients with acute coronary syndrome and those with stable disease (24.1% vs 28.2%, P  = 0.32)., Conclusions: Approximately one-quarter of AF patients undergoing PCI are treated with dual-pathway therapy in Canadian practice, with its use increasing during the studied period. Patients selected for dual-pathway therapy have less-complex coronary disease history and intervention., (© 2021 The Authors.)

Background: The current Canadian Cardiovascular Society antiplatelet therapy guidelines recommend the use of ticagrelor or prasugrel over clopidogrel as first-line platelet P2Y12 receptor antagonists for treatment of moderate- to high-risk acute coronary syndromes. Recently, Effient (prasugrel [Eli Lilly Canada Inc, Toronto, Canada]) was discontinued by its distributor in Canada., Methods: Five members of the Canadian Cardiovascular Society antiplatelet therapy 2018 guidelines committee undertook an independent, evidence-based review to outline patients for whom prasugrel should be the optimal P2Y12 agent and discuss alternative strategies to consider without prasugrel., Results: Several clinical scenarios where prasugrel should be indicated are identified and discussed. Considerations to be undertaken for alternative therapies are summarized, including a review of national and international guidelines for de-escalation of P2Y12 receptor antagonists., Conclusions: The discontinuation of prasugrel poses a challenge for clinicians. Clinicians must consider key factors in determining the best alternate therapy., (© 2021 The Authors.)

Background: Management of ST-elevated myocardial infarction (STEMI) necessitates rapid reperfusion. Delays prolong myocardial ischemia and increase the risk of complications, including death. The COVID-19 pandemic may have impacted STEMI management. We evaluated the relative volume of hospitalizations and clinical time intervals within a regional STEMI system., Methods: 494 patients with STEMI were grouped into pre-lockdown, lockdown and re-opening cohorts. Clinical, temporal and outcome data were collected and compared between groups for both urban and rural patients, receiving primary percutaneous coronary intervention (PCI) and pharmacoinvasive revascularization, respectively. Data was compared to a 10-year historical comparator., Results: During pre-lockdown there was 238 cases versus 193 in lockdown; a 19.0% reduction in volume. When lockdown was compared to the median caseload from a 10-year historical cohort, a 19.8% reduction was observed. For patients treated with primary PCI during lockdown, median symptom-to-balloon time increased by 44-minutes [217 (IQR 157-387) vs. 261 (160-659) minutes; p=0.03]; driven by an increase in median symptom-to-door time of 41-minutes [136 (IQR 80-267) vs. 177 (IQR 90-569) minutes; p<0.01]. Only patients transferred from non-PCI facilities demonstrated an increase in door-to-reperfusion time [116 (IQR 93-150) vs. 139 (IQR 100-199) minutes; p<0.01]. More patients had left ventricular dysfunction during the lockdown [35% vs. 44%; p=0.04], but there was no difference in mortality., Conclusion: During the COVID-19 lockdown, fewer patients presented with STEMI. Time-to-reperfusion was significantly prolonged and appeared driven predominantly by patient-level and transfer delays. Public education and systems-level changes will be integral to STEMI care during the second wave of COVID-19., (© 2020 Published by Elsevier Inc. on behalf of the Canadian Cardiovascular Society.)

The vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation level is a highly specific method to assess P2Y12 receptor inhibition. Traditionally, VASP phosphorylation is analyzed by flow cytometry, which is laborious and restricted to specialized laboratories. Recently, a simple ELISA kit has been commercialized. The primary objective of this study was to compare the performance of VASP assessment by ELISA and flow cytometry in relation to functional platelet aggregation testing by Multiplate ® whole-blood aggregometry. Blood from 24 healthy volunteers was incubated with increasing concentration of a P2Y12 receptor inhibitor (AR-C 66096). Platelet function testing was carried out simultaneously by Multiplate ® aggregometry and by VASP assessment through ELISA and flow cytometry. As expected, increasing concentrations of the P2Y12 receptor inhibitor induced a proportional inhibition of platelet aggregation and P2Y12 receptor activation across the modalities. Platelet reactivity index values of both ELISA- and flow cytometry-based VASP assessment methods correlated strongly ( r = 0.87, p < 0.0001) and showed minimal bias (1.05%). Correlation with Multiplate ® was slightly higher for the flow cytometry-based VASP assay ( r = 0.79, p < 0.0001) than for the ELISA-based assay ( r = 0.69, p < 0.0001). Intraclass correlation (ICC) was moderate for all the assays tested (ICC between 0.62 and 0.84). However, categorization into low, optimal, or high platelet reactivity based on these assays was strongly concordant (κ between 0.86 and 0.92). In conclusion, the consensus-recommended assays with their standardized cut-offs should not be used interchangeably in multi-center clinical studies but, rather, they should be standardized throughout sites., Competing Interests: J.F.T. has received research grants for his institution from Abbott Vascular, Biosensors, Idorsia, and Novartis and has received scientific advisory board or speaker honoraria from Abbott Vascular, Bayer, Bristol-Myers Squibb-Pfizer Alliance, AstraZeneca, Servicer, Novartis, and Daiichi-Sankyo. D.S. has received unrestricted grant support (physician-initiated grant) from Eli Lilly Canada, Aggredyne, Spartan Biosciences, and Diapharma/Roche Diagnostics and is a member of the advisory board and has received honoraria from AstraZeneca, Bayer, Abbott Vascular. M.L. has received speaker honoraria from Bayer, has participated in industry-funded trials from Idorsia, and has received in-kind and financial support for investigator-initiated grants from Leo Pharma, Roche Diagnostics, and Aggredyne. The remaining authors declare no conflict of interest.

Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y 12 receptor inhibitor is the standard treatment for patients undergoing percutaneous coronary intervention. The availability of different P2Y 12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor) with varying levels of potency has enabled physicians to contemplate individualized treatment regimens, which may include escalation or de-escalation of P2Y 12 -inhibiting therapy. Indeed, individualized and alternative DAPT strategies may be chosen according to the clinical setting (stable coronary artery disease vs. acute coronary syndrome), the stage of the disease (early- vs. long-term treatment), and patient risk for ischemic and bleeding complications. A tailored DAPT approach may be potentially guided by platelet function testing (PFT) or genetic testing. Although the routine use of PFT or genetic testing in percutaneous coronary intervention-treated patients is not recommended, recent data have led to an update in guideline recommendations that allow considering selective use of PFT for DAPT de-escalation. However, guidelines do not expand on when to implement the selective use of such assays into decision making for personalized treatment approaches. Therefore, an international expert consensus group of key leaders from North America, Asia, and Europe with expertise in the field of antiplatelet treatment was convened. This document updates 2 prior consensus papers on this topic and summarizes the contemporary updated expert consensus recommendations for the selective use of PFT or genotyping in patients undergoing percutaneous coronary intervention., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with stenting requires consideration of patient characteristics, and decision makers require a comprehensive overview of the evidence., Methods: We performed an umbrella review of systematic reviews (SRs) of randomized controlled trials of extended DAPT (> 12 months) compared with DAPT for 6 to 12 months after percutaneous coronary intervention with stenting. Outcomes of interest were death, myocardial infarction (MI), stroke, stent thrombosis, major adverse cardiac and cerebrovascular events, bleeding, and urgent revascularization. We aimed to assess the evidence of benefits and harms among clinically important subgroups (eg, elderly patients, those with diabetes, prior MI, acute coronary syndrome). We assessed the quality of the included reviews by use of A Measurement Tool to Assess Systematic Reviews (AMSTAR)., Results: Sixteen SRs involving 8 randomized controlled trials were included. Most scored 7 or more points on the AMSTAR checklist. There was no significant difference in outcomes with extended DAPT compared with 6 months of DAPT in most SRs, with the exception of an increased risk of major bleeding. Compared with 12 months, extended DAPT may reduce the risk of MI and stent thrombosis; however, the findings were not consistent across all reviews. There have been conflicting reports of an increased risk of death with extended DAPT. Few SRs assessed outcomes among patient subgroups., Conclusions: Extended DAPT may reduce the risk of MI and stent thrombosis but increase the risk of major bleeding and death. Whether the effects of extended DAPT are consistent across patient subgroups is unclear, and future SRs should address this knowledge gap., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background To manage overcrowding and bed shortages in Canadian hospitals, same-day discharge (SDD) after percutaneous coronary intervention (PCI) has emerged as a solution to improve resource utilization. However, limited information exists regarding current trends, hospital variation, and safety of SDD PCI in Canada. Methods and Results We evaluated outpatients undergoing elective PCI in Ontario, Canada, from October 2008 to March 2016. SDD was defined when patients were discharged on the day of PCI, and non-SDD was defined as those patients who had 1 overnight stay. The primary outcome was 30-day all-cause death or hospitalization for acute coronary syndrome. Inverse probability of treatment weighting with propensity score was used to account for differences in baseline and clinical characteristics between SDD and non-SDD groups. Among 35 972 patients who underwent elective PCI at 17 PCI centers in Ontario, 10 801 patients (30%) had SDD PCI and 25 121 patients (70%) had non-SDD PCI. Substantial hospital variation for SDD PCI was observed, ranging from 0% to 87% during the study period. In the propensity-weighted cohort, SDD patients had no significant difference in 30-day rates of death or hospitalization for acute coronary syndrome (1.3% versus 1.6%; hazard ratio: 0.84 [95% CI, 0.65-1.08]; P=0.17) compared with non-SDD patients. SDD and non-SDD patients also had no significant difference in 30-day rates of mortality or coronary revascularization. Conclusions In this large population-based cohort of elective PCI patients, we demonstrated the safety of SDD PCI. Increased adoption of this strategy could lead to improved bed-flow efficiency and substantial savings for the Canadian healthcare system without comprising outcomes.

Introduction: Dual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting; however, there is ongoing debate about the optimal duration, especially in specific patient groups. In the proposed systematic review, we intend to assess the optimal duration of DAPT following PCI with stenting, with a focus on clinically relevant patient subgroups., Methods and Analysis: We will perform a comprehensive search of the published literature for randomised controlled trials (RCTs) assessing the benefits and harms of extended DAPT (>12 months) compared with short-term DAPT (6-12 months) following PCI with stenting (bare metal or drug eluting). ClinicalTrials.gov and ICTRP will also be searched to identify ongoing and completed clinical trials. Two independent reviewers will select studies for inclusion, and the risk of bias will be assessed by use of Cochrane's Risk of Bias tool. The primary outcome of interest is death (all-cause, cardiovascular, non-cardiovascular). Secondary outcomes are bleeding (major, minor, gastrointestinal), urgent target vessel revascularisation, major adverse cardiovascular events, myocardial infarction, stroke and stent thrombosis. Subgroup data will be sought for patients with prior myocardial infarction, acute coronary syndrome at presentation and diabetes, and based on smoking status and age group. Data will be analysed by random-effects meta-analysis, and separate analyses will be performed for patient subgroups. Bayesian network meta-analysis will be performed to investigate the effect of individual P2Y12 inhibitors at different DAPT durations longer than 6 months., Ethics and Dissemination: This review will provide a comprehensive overview of the available evidence of the benefits and harms associated with extending DAPT beyond 12 months following PCI with stenting and the effects on clinically important subgroups. The results of this review will inform clinical and policy decisions regarding the optimal treatment duration of DAPT following PCI with stenting., Systematic Review Registration: PROSPERO no. CRD42018082587., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Common genetic variation in CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) *2 and *3 alleles leads to a loss of functional protein, and carriers of these loss-of-function alleles when treated with clopidogrel have significantly reduced clopidogrel active metabolite levels and high on-treatment platelet reactivity resulting in increased risk of major adverse cardiovascular events, especially after percutaneous coronary intervention. The Food and Drug Administration has issued a black box warning advising practitioners to consider alternative treatment in CYP2C19 poor metabolizers who might receive clopidogrel and to identify such patients by genotyping. However, routine clinical use of genotyping for CYP2C19 loss-of-function alleles in patients undergoing percutaneous coronary intervention is not recommended by clinical guidelines because of lack of prospective evidence. To address this critical gap, TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention) is a large, pragmatic, randomized trial comparing point-of-care genotype-guided antiplatelet therapy with routine care to determine whether identifying CYP2C19 loss-of-function allele patients prospectively and prescribing alternative antiplatelet therapy is beneficial.

Objectives: A 6-month weight-management program with full meal replacement, low-calorie diet (full MR-LCD) (900 kcal/day for 6 to 12 weeks) follows a protocol for patients with diabetes for decreasing or discontinuing weight-gaining diabetes medications first (Group WG) and then titrating weight-neutral medications (Group WN)., Methods: This is a retrospective cohort study (1992 to 2009) of weight, glycemic control and diabetes medications changes in 317 patients with obesity and type 2 diabetes who were taking medications., Results: Group WG and Group WN were similar at baseline, except that glycated hemoglobin (A1C) levels were significantly lower in Group WN (7.5% vs. 6.6%; p<0.001). At 6 months, both groups had lost 16% of their weight, and the decreases or discontinuations of medications were 92.1% sulfonureas, 86.5% insulins, 78.8% thiazolidinediones, 77.8% alpha-glucosidase inhibitors, 50% meglitinides, 33.3% dipeptidyl peptidase-4 (DPP-4) inhibitors and 32.8% metformin. At 6 months, compared with baseline, A1C levels improved in Group WG and Group WN (6-month A1C levels 6.7% and 5.8%, respectively; p<0.0001), and Group WN had significantly better A1C levels than Group WG. At 6 months, 30% of patients were no longer taking diabetes medications and had significantly better percentages of weight loss compared with those taking medications (18.6% vs. 16%; p=0.002); both groups had improved glycemic control at 6 months (A1C 6.0% vs. A1C 6.6%; NS)., Conclusions: In patients with obesity and type 2 diabetes taking medications, a full MR-LCD program appears to be safe and includes improvement in A1C levels. At 6 months, the percentage of weight loss can be significantly better in patients who no longer require diabetes medications, and A1C levels are best controlled in patients who are on WN medications., (Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)

Dual antiplatelet therapy with aspirin and a P2Y 12 inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y 12 inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y 12 inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y 12 inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y 12 inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y 12 inhibitors., (© 2017 American Heart Association, Inc.)

Purpose of Review: Platelet P2Y12 receptor inhibitors are routinely prescribed for patients after acute coronary syndromes and percutaneous coronary interventions. Patients may have underresponsiveness (or resistance) to these drugs and in particular to clopidogrel, the most often used type. This review aims to focus on the concept of P2Y12 receptor inhibitor resistance and discuss incidence, mechanisms, novel diagnostic techniques and past and future clinical trials on the topic., Recent Findings: Patients treated with P2Y12 receptor inhibitors may develop high on-treatment platelet reactivity (HPR), a phenomenon of impaired response toward the drug, which has been associated with ischemic complications. Although potent P2Y12 inhibitors provide better ischemic protection, this must be balanced with increased bleeding risk. Several clinical factors, including common genetic variants such as Cytochrome P450 2C19 loss-of-function alleles, have been shown to predispose to HPR among patients on clopidogrel. Platelet function tests and genotyping platforms have enabled identification of patients at-risk for HPR. Past studies using platelet testing and tailoring therapy among patients with HPR have failed to provide conclusive data to support its routine use., Summary: Ongoing studies using genotyping and novel antiplatelet regimens may identify potential strategies to minimize ischemic and bleeding risks concurrently. Until definitive studies demonstrate clear benefit of a personalized approach to P2Y12 inhibitor prescription, the choice of P2Y12 inhibitors should continue to be based on best evidence from previous large clinical trials.