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Abstract Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated reduction in heart failure outcomes in patients with type 2 diabetes mellitus, although the exact mechanism of benefit remains unclear. Alteration in left atrial (LA) function due to chronic pressure or volume overload is a hallmark of heart failure. Objective To evaluate the effect of the SGLT2 inhibitor empagliflozin on LA volume and function. Methods 90 patients with coronary artery disease and type 2 diabetes (T2DM) were randomized to empagliflozin (n = 44) or placebo (n = 46), and underwent cardiac magnetic resonance (CMR) imaging at baseline and after 6 months. The main outcome was change in LA volume; LA function, including active and passive components, was also measured by a blinded reader. Results At baseline, there was no significant difference in LA volumes between the empagliflozin (indexed maximum LA volume 26.4 ± 8.4mL/m2, minimum LA volume 11.1 ± 5.7mL/m2) and placebo (indexed maximum LA volume 28.7 ± 8.2mL/m2, minimum LA volume 12.6 ± 5.0mL/m2) groups. After 6 months, changes in LA volumes did not differ with adjusted difference (empagliflozin minus placebo): 0.99 mL/m2 (95% CI: -1.7 to 3.7 mL/m2; p = 0.47) for indexed maximum LA volume, and 0.87 mL/m2 (95% CI: -0.9 to 2.6 mL/m2; p = 0.32) for indexed minimum LA volume. Changes in total LA emptying fraction were also similar, with between-group adjusted mean difference − 0.01 (95% CI: -0.05 to 0.03, p = 0.59). Conclusion SGLT2 inhibition with empagliflozin for 6 months did not have a significant impact on LA volume and function in patients with T2DM and coronary artery disease. (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes [EMPA-HEART]; NCT02998970).

Background: Patients with atrial fibrillation (AF) after an acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI) with multiple comorbidities are at increased risk for bleeding and ischemic events. Objectives: This post-hoc analysis of AUGUSTUS describes the safety and efficacy of antithrombotic regimens in patients with multimorbidity. Methods: AUGUSTUS was a 2 × 2 factorial, randomized controlled trial evaluating the safety of apixaban vs vitamin K antagonists (VKA) (open-label) and aspirin vs placebo (double-blind) in patients with AF and ACS and/or PCI treated with a P2Y12 inhibitor. Patients were categorized as having no multimorbidity (0-2 comorbidities), moderate multimorbidity (3-4 comorbidities), or high multimorbidity (≥5 comorbidities). The associations between multimorbidity and clinical outcomes and interactions with antithrombotic regimens were tested. Results: Of 4,493 patients (97.4%) with available comorbidity data, 1,897 (42.2%) had no multimorbidity, 2,110 (47%) had moderate, and 486 (10.8%) had high multimorbidity. Patients with moderate (HR: 1.23; 95% CI: 1.02-1.47) and high (HR: 1.98; 95% CI: 1.55-2.54) multimorbidity had higher rates of International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant nonmajor (CRNM) bleeding compared to patients with no multimorbidity. No significant interaction between multimorbidity and apixaban vs vitamin K antagonists was observed for ISTH major bleeding/CRNM (Pint = 0.415), death or hospitalization (Pint = 0.092), or death or ischemic event (Pint = 0.299). Similarly, no significant interaction between multimorbidity and aspirin vs placebo was seen for ISTH major bleeding/CRNM (Pint = 0.261), death or hospitalization (Pint = 0.646), or death or ischemic event (Pint = 0.608). Conclusions: Our findings support the standard use of apixaban plus a P2Y12 inhibitor in patients with AF and ACS/PCI, irrespective of the presence of multimorbidity.

Countries face challenges in paying for new drugs. High prices are driven in part by exploding drug development costs, which, in turn, are driven by essential but excessive regulation. Burdensome regulation also delays drug development, and this can translate into thousands of life-years lost. We need system-wide reform that will enable less expensive, faster drug development. The speed with which COVID-19 vaccines and AIDS therapies were developed indicates this is possible if governments prioritize it. Countries also differ in how they value drugs, and generally, those willing to pay more have better, faster access. Canada is used as an example to illustrate how “incremental cost-effectiveness ratios” (ICERs) based on measures such as gains in “quality-adjusted life-years” (QALYs) may be used to determine a drug’s value but are often problematic, imprecise assessments. Generally, ICER/QALY estimates inadequately consider the impact of patient crossover or long post-progression survival, therapy benefits in distinct subpopulations, positive impacts of the therapy on other healthcare or societal costs, how much governments willingly might pay for other things, etc. Furthermore, a QALY value should be higher for a lethal or uncommon disease than for a common, nonlethal disease. Compared to international comparators, Canada is particularly ineffective in initiating public funding for essential new medications. Addressing these disparities demands urgent reform.

Background Days alive out of hospital (DAOH) is an objective and patient‐centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations. Methods and Results ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was an international double‐blind, double‐dummy randomized clinical trial that compared rivaroxaban with warfarin in patients with atrial fibrillation at increased risk for stroke. We assessed DAOH using investigator‐reported event data for up to 12 months after randomization in ROCKET AF. We assessed DAOH overall, by treatment group, and by subgroup, including age, sex, and comorbidities, using Poisson regression. The mean±SD number of days dead was 7.3±41.2, days hospitalized was 1.2±7.2, and mean DAOH was 350.7±56.2, with notable left skew. Patients with comorbidities had fewer DAOH overall. There were no differences in DAOH by treatment arm, with mean DAOH of 350.6±56.5 for those randomized to rivaroxaban and 350.7±55.8 for those randomized to warfarin (P=0.86). A sensitivity analysis found no difference in DAOH not disabled with rivaroxaban versus warfarin (DAOH not disabled, 349.2±59.5 days and 349.1 days±59.3 days, respectively, P=0.88). Conclusions DAOH did not identify a treatment difference between patients randomized to rivaroxaban versus warfarin. This may be driven in part by the low overall event rates in atrial fibrillation anticoagulation trials, which leads to substantial left skew in measures of DAOH.

Abstract Introduction The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on maximally tolerated statins, adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is recommended. This population-based, real-world study examined cardiovascular (CV) events in patients with ASCVD who are on statins and above current guideline threshold LDL-C levels. Methods Using administrative health data in Alberta, Canada, we identified patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8 mmol/L on statins between April 1, 2010 and March 31, 2016. Exploratory subgroups included very high-risk patients with ASCVD shown to derive the most benefit from PCSK9i intensification as identified by the CCS guidelines, including those with acute coronary syndrome (ACS) or recent MI. Frequencies and rates of individual and composite CV events (primary outcome: MI, IS, hospitalization for unstable angina, coronary revascularization, cardiovascular death; secondary outcome: MI, IS, CV death) were calculated over follow-up. Results The study included 32,984 patients with a mean (standard deviation) follow-up of 40.8 (21.0) months. Overall, 17.7% and 15.6% experienced a primary and secondary outcome, respectively, with rates of 5.58 and 4.83 per 100 patient-years, respectively. CV death and MI were the most common events. Subgroups with recurrent MI and comorbid diabetes exhibited higher CV event rates (23.6% and 22.2% had a primary outcome, respectively). Rates of CV events were notably high in patients with ACS or recent MI (49.4% and 54.0% had a primary outcome, respectively). Conclusion This real-world study confirms that statin-treated high-risk patients with ASCVD and above-threshold LDL-C levels have substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to reduce CV risk.

Abstract Background Some data suggest that low levels of low-density lipoprotein cholesterol (LDL-C) are associated with risk of cataracts. Proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors reduce LDL-C below levels achieved with statins alone. We determined whether the incidence of cataracts was influenced by treatment with the PCSK9 inhibitor alirocumab versus placebo, and whether that incidence was affected by achieved LDL-C levels. Methods The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome receiving high-intensity or maximum-tolerated statin. Incident cataracts were pre-specified events of interest. In multivariable analysis using propensity score-matching on characteristics including cataract risk factors, incident cataracts were compared in the alirocumab and placebo groups according to LDL-C levels achieved with alirocumab. Results Over median follow-up of 2.8 years (interquartile range 2.3 − 3.4), the incidence of cataracts was similar with alirocumab (127/9462 [1.3%]) versus placebo (134/9462 [1.4%]); hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.74 − 1.20). In patients treated with alirocumab with ≥ 2 LDL-C values

OBJECTIVES:. Treatments that prevent sepsis complications are needed. Circulating lipid and protein assemblies—lipoproteins play critical roles in clearing pathogens from the bloodstream. We investigated whether early inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) may accelerate bloodstream clearance of immunogenic bacterial lipids and improve sepsis outcomes. DESIGN:. Genetic and clinical epidemiology, and experimental models. SETTING:. Human genetics cohorts, secondary analysis of a phase 3 randomized clinical trial enrolling patients with cardiovascular disease (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402), and experimental murine models of sepsis. PATIENTS OR SUBJECTS:. Nine human cohorts with sepsis (total n = 12,514) were assessed for an association between sepsis mortality and PCSK9 loss-of-function (LOF) variants. Incident or fatal sepsis rates were evaluated among 18,884 participants in a post hoc analysis of ODYSSEY OUTCOMES. C57BI/6J mice were used in Pseudomonas aeruginosa and Staphylococcus aureus bacteremia sepsis models, and in lipopolysaccharide-induced animal models. INTERVENTIONS:. Observational human cohort studies used genetic PCSK9 LOF variants as instrumental variables. ODYSSEY OUTCOMES participants were randomized to alirocumab or placebo. Mice were administered alirocumab, a PCSK9 inhibitor, at 5 mg/kg or 25 mg/kg subcutaneously, or isotype-matched control, 48 hours prior to the induction of bacterial sepsis. Mice did not receive other treatments for sepsis. MEASUREMENTS AND MAIN RESULTS:. Across human cohort studies, the effect estimate for 28-day mortality after sepsis diagnosis associated with genetic PCSK9 LOF was odds ratio = 0.86 (95% CI, 0.67–1.10; p = 0.24). A significant association was present in antibiotic-treated patients. In ODYSSEY OUTCOMES, sepsis frequency and mortality were infrequent and did not significantly differ by group, although both were numerically lower with alirocumab vs. placebo (relative risk of death from sepsis for alirocumab vs. placebo, 0.62; 95% CI, 0.32–1.20; p = 0.15). Mice treated with alirocumab had lower endotoxin levels and improved survival. CONCLUSIONS:. PCSK9 inhibition may improve clinical outcomes in sepsis in preventive, pretreatment settings.

Abstract We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction

The government of Canada now plans to bring into force new federal drug pricing regulations on 1 July 2022. We do not take issue with the goal of medication affordability, which is vital in healthcare the world over. Our concern is that the new guidelines are being implemented without due consideration for three major unintended consequences: regulatory changes will lower the number of clinical trials for new medications in Canada, fewer clinical trials will mean lower research and development investments, and changes will reduce patients’ access to new medications. Access to effective medications is a cornerstone of healthcare for Canadian patients. As physicians, our duty to patient care demands that we tell the government to protect the right of Canadians to timely access to life-changing medicines.

Abstract Background Structured risk-stratification to guide clinician assessment and engagement with evidence-based therapies may reduce care variance and improve patient outcomes for Acute Coronary Syndrome (ACS). The Australian Grace Risk score Intervention Study (AGRIS) explored the impact of the GRACE Risk Tool for stratification of ischaemic and bleeding risk in ACS. While hospitals in the active arm had a higher overall rate of invasive ACS management, there was neutral impact on important secondary prevention prescriptions/referrals, hospital performance measures, myocardial infarction and 12-month mortality leading to early trial cessation. Given the Grace Risk Tool is under investigation internationally, this process evaluation study provides important insights into the possible contribution of implementation fidelity on the AGRIS study findings. Methods Using maximum variation sampling, five hospitals were selected from the 12 centres enrolled in the active arm of AGRIS. From these facilities, 16 local implementation stakeholders (Cardiology advanced practice nurses, junior and senior doctors, study coordinators) consented to a semi-structured interview guided by the Theoretical Domains Framework. Directed Content Analysis of qualitative data was structured using the Capability/Opportunity/Motivation-Behaviour (COM-B) model. Results Physical capability was enhanced by tool usability. While local stakeholders supported educating frontline clinicians, non-cardiology clinicians struggled with specialist terminology. Physical opportunity was enhanced by the paper-based format but was hampered when busy clinicians viewed risk-stratification as one more thing to do, or when form visibility was neglected. Social opportunity was supported by a culture of research/evidence yet challenged by clinical workflow and rotating medical officers. Automatic motivation was strengthened by positive reinforcement. Reflective motivation revealed the GRACE Risk Tool as supporting but potentially overriding clinical judgment. Divergent professional roles and identity were a major barrier to integration of risk-stratification into routine Emergency Department practice. The cumulative result revealed poor form completion behaviors and a failure to embed risk-stratification into routine patient assessment, communication, documentation, and clinical practice behaviors. Conclusions Numerous factors negatively influenced AGRIS implementation fidelity. Given the prominence of risk assessment recommendations in United States, European and Australian guidelines, strategies that strengthen collaboration with Emergency Departments and integrate automated processes for risk-stratification may improve future translation internationally.

Background: Cardiovascular disease is the second-leading cause of death in Canada. However, limited data are available on the prevalence of atherosclerotic cardiovascular disease (ASCVD) in Canada. The study objective was to describe the incidence and prevalence of ASCVD in adult patients in Ontario, Canada, and to evaluate temporal trends for subsequent ASCVD events among those with new-onset ASCVD. Methods: This retrospective, observational study identified ASCVD incidence and prevalence data from the Institute for Clinical Evaluative Sciences Data Repository for adults from Ontario. Overall prevalence was established for the period from 2002 to 2018. Incident cases from April 1, 2005 to March 2016 were then identified, and followed up to 2018. Primary outcomes were date and type of index event/procedure, patient characteristics/baseline demographics, and comorbidities. Secondary outcomes assessed were time from first to second ASCVD event, subsequent event(s) and/or mortality, and type of subsequent event(s) relative to the type of index/primary event. Results: A total of 1,042,621 eligible prevalent ASCVD cases were identified; of these, 743,309 patients (69%) were newly diagnosed with incident ASCVD. The 10-year prevalence rates for all ASCVD subtypes increased over the study period. Overall event incidence rates per 1000 person-years were mostly stable or increased. Among incident cases, 50% experienced subsequent events over the study period. Conclusions: This observational study demonstrated increasing prevalence and high incidence of new ASCVD diagnoses in adults from Ontario, over the study period. These data, together with the substantial number of subsequent events in ASCVD patients, demonstrate significant clinical burden of this disease in Ontario. Résumé: Contexte: Les maladies cardiovasculaires constituent la deuxième cause de décès au Canada. Toutefois, on dispose de peu de données sur la prévalence de la maladie cardiovasculaire athéroscléreuse (MCVAS) au Canada. L’étude avait pour objectifs de décrire l’incidence et la prévalence de la MCVAS chez les patients adultes en Ontario (Canada) et d’évaluer les tendances temporelles des manifestations subséquentes de MCVAS chez les personnes ayant une MCVAS d’apparition récente. Méthodologie: Cette étude observationnelle rétrospective a permis de colliger les données sur l’incidence et la prévalence de la MCVAS chez les adultes ontariens consignées dans le référentiel de l’Institut des sciences cliniques évaluatives. La prévalence globale a été établie pour la période allant de 2002 à 2018. Les cas incidents survenus du 1er avril 2005 à mars 2016 ont ensuite été recensés et suivis jusqu’en 2018. Les paramètres d’évaluation principaux étaient : date et nature de la manifestation index et de l’intervention; caractéristiques des patients et données démographiques initiales; comorbidités. Les éléments suivants constituaient les paramètres d’évaluation secon-daires : temps écoulé entre la première et la deuxième manifestation de MCVAS, la ou les manifestations subséquentes et/ou le décès; nature de la ou des manifestations subséquentes par rapport à celle de la manifestation index ou primaire. Résultats: En tout, 1 042 621 cas de MCVAS prévalents admissibles ont été dénombrés; parmi ceux-ci, il y avait 743 309 (69 %) cas incidents de MCVAS nouvellement diagnostiqués. Les taux de prévalence à 10 ans de tous les sous-types de MCVAS ont augmenté au cours de la période étudiée. Les taux globaux d’incidence des manifestations par 1000 années-personnes étaient généralement stables ou accrus. Cinquante pour cent des cas incidents ont été associés à des manifestations subséquentes au cours de la période étudiée. Conclusions: Cette étude observationnelle a démontré une prévalence croissante et une incidence élevée de nouveaux diagnostics de MCVAS chez les adultes en Ontario au cours de la période étudiée. Les données à cet égard, ainsi que le grand nombre de manifestations subséquentes de la maladie, démontrent que la MCVAS constitue un fardeau clinique considérable en Ontario.

Background: Data are limited data on the prevalence of cardiovascular disease (CVD) and multimorbidity in contemporary cohorts of high-cost users (HCUs) in Canada.We examined the following: (i) the prevalence of CVD, with a comparison of total healthcare costs among HCUs with vs without CVD; (ii) the contribution of other comorbidities to costs among HCUs with CVD; and (iii) the trajectory of healthcare costs in the years before and after becoming an HCU. Methods: The study included adult Alberta patients in the Canadian Institutes of Health Research/Canadian Institute for Health Information Dynamic Cohort of Complex, High System Users from 2011-2012 through 2014-2015. We examined total healthcare costs, including hospital, ambulatory care, physician services, and drugs. Results: Among 88,536 HCUs, 23.4% had no CVD, 28.9% were hospitalized with a primary diagnosis of CVD, and 47.7% were hospitalized with a secondary diagnosis of CVD. Total healthcare costs were $2.0 billion (20.4% non-hospital costs), $2.8 billion (24.1% non-hospital costs), and $4.9 billion (19.8% non-hospital costs), respectively, in the 3 groups. Many HCUs with CVD were frail (74.2%) and many had diabetes (33.8%) or chronic obstructive pulmonary disease (27.9%), which contributed to higher costs and mortality. Healthcare expenditures in HCUs with CVD were several times higher than per capita health expenditures in the years prior to, and following, their inclusion in the dynamic HCU cohort. Conclusions: CVD is very common in HCUs of healthcare. HCUs with CVD have high rates of frailty and multimorbidity. Further research is needed to identify and intervene earlier, in order to flatten the cost curve in these complex patients. Résumé: Introduction: Les données sur la prévalence des maladies cardiovasculaires (MCV) et de la multimorbidité au sein des cohortes contemporaines de grands utilisateurs (GU) du Canada sont limitées. Nous avons examiné ce qui suit : (i) la prévalence des MCV en comparant les coûts totaux des soins de santé entre les GU atteints de MCV et les GU non atteints de MCV; (ii) la contribution des autres comorbidités aux coûts liés aux GU atteints de MCV; (iii) la trajectoire des coûts des soins de santé dans les années avant et après avoir été considérés comme un GU. Méthodes: L’étude portait sur des patients adultes de l’Alberta de la Cohorte dynamique de grands utilisateurs du système de santé aux besoins complexes de 2011-2012 à 2014-2015 des Instituts de recherche en santé du Canada et de l’Institut canadien d’information sur la santé. Nous avons examiné les coûts totaux des soins de santé, notamment les coûts hospitaliers, les coûts des soins ambulatoires, des services médicaux et des médicaments. Résultats: Parmi les 88 536 GU, 23,4 % n’avaient pas de MCV, 28,9 % étaient hospitalisés et avaient un diagnostic principal de MCV, et 47,7 % étaient hospitalisés et avaient un diagnostic secondaire de MCV. Les coûts totaux des soins de santé des 3 groupes étaient respectivement de 2,0 G$ (20,4 % de coûts non hospitaliers), 2,8 G$ (24,1 % de coûts non hospitaliers) et 4,9 G$ (19,8 % de coûts non hospitaliers). Plusieurs GU atteints de MCV étaient fragiles (74,2 %) et beaucoup avaient le diabète (33,8 %) ou une maladie pulmonaire obstructive chronique (27,9 %), qui contribuaient à des coûts et à une mortalité plus élevés. Les dépenses de santé par personne liées aux GU atteints de MCV étaient beaucoup plus élevées que les dépenses de santé par personne dans les années qui précédaient ou suivaient leur inclusion dans la cohorte dynamique de GU atteints de MCV. Conclusions: Les GU de soins de santé sont très fréquemment atteints de MCV. Les GU atteints de MCV présentent des taux de fragilité et de multimorbidité élevés. D’autres recherches sont nécessaires pour cerner et intervenir plus tôt afin d’aplatir la courbe des coûts chez ces patients aux besoins complexes.

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 Coordinated National Network to Engage Interventional Cardiologists in the Antithrombotic Treatment of Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) study, to determine patterns of initial antithrombotic therapy selection. Results: The median (25th, 75th percentile) CHADS2 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. Résumé: Introduction: Les patients atteints de fibrillation auriculaire (FA) qui subissent une intervention coronarienne percutanée (ICP) et choisissent un schéma posologique antithrombotique ont besoin de peser les risques d’événements cardiaques d’origine ischémique, d’accidents vasculaires cérébraux et d’hémorragies. Méthodes: Les 467 patients atteints de FA ayant subi une ICP de décembre 2015 à juillet 2018 qui ont fait l’objet de notre étude ont été trouvés lors de la vérification des dossiers par 47 cardiologues canadiens de l’étude CONNECT AF+PCI (Coordinated National Network to Engage Interventional Cardiologists in the Antithrombotic Treatment of Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) pour déterminer les schémas de sélection du traitement antithrombotique initial. Résultats: Le score CHADS2 médian (25e, 75e percentile) était de 2 (1, 3), et l’ICP avait été réalisée dans le cadre du syndrome coronarien aigu chez 62,1 % des patients. La trithérapie antithrombotique (TTA) était le traitement initial chez 62,7 % des patients, la bithérapie, chez 25,7 % des patients, et la bithérapie antiplaquettaire, chez 11,6 % des patients, mais il y avait une augmentation temporelle dans l’utilisation de la bithérapie durant l’étude; la durée médiane prévue de la TTA était de 1 (1, 3) mois. Comparativement aux patients sélectionnés pour la TTA, les patients sélectionnés pour la bithérapie étaient moins susceptibles d’avoir eu un infarctus du myocarde précédent (35,8 % vs 25,8 %, P = 0,045) et une ICP précédente (33,8 % vs 23,3 %, P = 0,03), et recevaient des endoprothèses de longueur totale plus courte (38 [23, 56] vs 30 [20, 46] mm, P = 0,03). Les patients sélectionnés pour la bithérapie montraient une prévalence plus élevée d’accidents vasculaires cérébraux/accidents ischémiques transitoires (13,0 % vs 23,3 %, P = 0,01). Il n’existait aucune différence dans la prévalence de l’anémie (21,5 % vs 25,8 %, P = 0,30). L’utilisation de la bithérapie était similaire chez les patients atteints d’un syndrome coronarien aigu et chez les patients dont la maladie était stable (24,1 % vs 28,2 %, P = 0,32). Conclusions: Dans la pratique canadienne, environ le quart des patients atteints de FA qui subissent une ICP sont traités par bithérapie, mais durant la période étudiée, son utilisation avait augmenté. Les patients sélectionnés pour la bithérapie ont des antécédents et des interventions liées aux maladies coronariennes moins complexes.

Background: Extension of dual antiplatelet therapy (DAPT) beyond 1 year after acute coronary syndrome is associated with a reduction in ischemic events but also increased bleeding. The DAPT score identifies individuals likely to derive overall benefit or harm from DAPT extension. We sought to evaluate the impact of providing the DAPT score to treating physicians on the decision to extend DAPT beyond 1 year after non–ST-segment elevation myocardial infarction. Methods: Moderate to high-risk non–ST-segment elevation myocardial infarction patients were enrolled from July 2016 to May 2018 in 13 Canadian hospitals by 52 cardiologists. Participating cardiologists were randomly assigned 1:1 to receive their individual patients’ DAPT scores before the 1-year follow-up visit vs not receiving their patients’ DAPT scores. Rates of DAPT extension were compared among the randomized groups. Results: At 1 year, 370 of the 585 (63.2%) patients discharged on DAPT were receiving DAPT. Among patients on DAPT at 1 year, the median (25th, 75th percentile) DAPT score was 2 (1,3). DAPT was extended beyond 1 year in 36.2% randomly assigned to provision of DAPT score vs 35.7% in the control group (P = 0.93). In the subgroup of patients with DAPT score ≥ 2, DAPT extension was 49.5% in the DAPT score provision arm vs 40.4% in the control arm (P = 0.22); among patients with DAPT score < 2, DAPT termination was 78.6% in the DAPT score provision arm vs 70.6% in the control arm (P = 0.26) (P value for interaction = 0.1). Conclusions: In this exploratory randomized trial, provision of the DAPT score to treating physicians had no impact on the duration of DAPT treatment beyond 1 year. Résumé: Introduction: La prolongation de la bithérapie antiplaquettaire au-delà d'un an après un syndrome coronarien aigu est associée à la réduction des accidents ischémiques, mais aussi à l’augmentation des hémorragies. Le score de bithérapie antiplaquettaire permet de déterminer les individus susceptibles d’obtenir des avantages globaux ou des inconvénients de la prolongation de la bithérapie antiplaquettaire. Nous avons cherché à évaluer les répercussions de l’obtention du score de bithérapie antiplaquettaire par les médecins traitants sur la décision quant à la prolongation de la bithérapie antiplaquettaire au-delà d'un an après l'infarctus du myocarde sans élévation du segment ST. Méthodes: De juillet 2016 à mai 2018, 52 cardiologues de 13 hôpitaux du Canada ont inscrit des patients exposés à un risque modéré à élevé d’infarctus du myocarde sans élévation du segment ST. Nous avons réparti de façon aléatoire selon un rapport 1:1 les cardiologues participants qui recevaient les scores de bithérapie antiplaquettaire individuels de leurs patients avant la consultation de suivi après un an vs ceux qui ne recevaient pas les scores de bithérapie antiplaquettaire de leurs patients. Nous avons comparé les taux de prolongation de la bithérapie antiplaquettaire des groupes répartis de façon aléatoire. Résultats: Après un an, 370 (63,2 %) patients sur 585 qui avaient eu à la sortie de l’hôpital une bithérapie antiplaquettaire recevaient la bithérapie antiplaquettaire. Parmi les patients qui prenaient la bithérapie antiplaquettaire après un an, le score médian de bithérapie antiplaquettaire (25e, 75e percentiles) était de 2 (1, 3). La bithérapie antiplaquettaire était prolongée au-delà d'un an chez 36,2 % des patients répartis de façon aléatoire qui avaient un score de bithérapie antiplaquettaire vs 35,7 % dans le groupe témoin (P = 0,93). Dans le sous-groupe de patients qui avaient un score de bithérapie antiplaquettaire ≥ 2, la prolongation de la bithérapie antiplaquettaire était de 49,5 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 40,4 % dans le bras témoin (P = 0,22); parmi les patients qui avaient un score de bithérapie antiplaquettaire < 2, la cessation de la bithérapie antiplaquettaire était de 78,6 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 70,6 % dans le bras témoin (P = 0,26) (valeur P pour l’interaction = 0,1). Conclusions: Dans cet essai exploratoire à répartition aléatoire, l’obtention du score de la bithérapie antiplaquettaire par les médecins traitants n’a pas engendré de répercussions sur la durée de la bithérapie antiplaquettaire au-delà d'un an.

Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial decreased major adverse cardiovascular events with very low‐dose rivaroxaban and aspirin in patients with coronary artery disease and peripheral artery disease. We examined the eligibility and potential real‐world impact of this strategy on the COMPASS‐eligible population. Methods and Results COMPASS eligibility criteria were applied to the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) registry, a population‐based cohort of Ontario adults. We compared 5‐year major adverse cardiovascular events and major bleeding rates stratified by COMPASS eligibility and by clinical risk factors. We applied COMPASS trial rivaroxaban/aspirin arm hazard ratios to estimate the potential impact on the COMPASS‐eligible cohort. Among 362 797 patients with coronary artery disease or peripheral artery disease, 38% were deemed eligible, 47% ineligible, and 15% indeterminate. Among eligible patients, a greater number of risk factors was associated with higher rates of cardiovascular outcomes, whereas bleeding rates increased minimally. Over 5 years, applying COMPASS treatment effects to eligible patients resulted in a 2.4% absolute risk reduction of major adverse cardiovascular events and a number needed to treat of 42, and a 1.3% absolute risk increase of major bleeding and number needed to harm (NNH) of 77. Those with at least 2 risk factors had a 3.0% absolute risk reduction of major adverse cardiovascular events (number needed to treat =34) and a 1.6% absolute risk increase of major bleeding (number needed to harm =61). Conclusions Implementation of very‐low‐dose rivaroxaban therapy would potentially impact ≈$$ \approx $$2 in 5 patients with atherosclerotic disease in Ontario. Eligible individuals with ≥$$ \ge $$2 comorbidities represent a high‐risk subgroup that may derive the greatest benefit‐to‐risk ratio. Selection of patients with high‐risk predisposing factors appears appropriate in routine practice.

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular events in type 2 diabetes (T2DM) and is associated with a reduction in left ventricular (LV) mass index. However, the impact on right ventricular (RV) remodeling is unknown. Accordingly, the objective of this study was to assess the impact of SGLT2 inhibition on RV parameters and function in T2DM and coronary artery disease (CAD). Methods In EMPA-HEART CardioLink-6, 97 patients with T2DM and CAD were randomly assigned to empagliflozin 10 mg (n = 49) once daily or placebo (n = 48). Cardiac magnetic resonance imaging was performed at baseline and after 6 months. RV mass index (RVMi), RV end-diastolic and end-systolic volume index (RVEDVi, RVESVi) and RV ejection fraction (RVEF) were assessed in blinded fashion. Results At baseline, mean RVMi (± SD) (11.8 ± 2.4 g/m2), RVEF (53.5 ± 4.8%), RVEDVi (64.3 ± 13.2 mL/m2) and RVESVi (29.9 ± 6.9 mL/m2) were within normal limits and were similar between the empagliflozin and placebo groups. Over 6 months, there were no significant differences in RVMi (− 0.11 g/m2, [95% CI − 0.81 to 0.60], p = 0.76), RVEF (0.54%, [95% CI − 1.4 to 2.4], p = 0.58), RVEDVi (− 1.2 mL/m2, [95% CI − 4.1 to 1.7], p = 0.41) and RVESVi (− 0.81 mL/m2, [95% CI − 2.5 to 0.90], p = 0.35) in the empaglifozin group as compared with the placebo group. In both groups, there was no significant correlation between RVMi and LVMi changes from baseline to 6 months. Conclusions In this post-hoc analysis, SGLT2 inhibition with empagliflozin had no impact on RVMi and RV volumes in patients with T2DM and CAD. The potentially differential effect of empagliflozin on the LV and RV warrants further investigation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT02998970?cond=NCT02998970&draw=2&rank=1 . Unique identifier: NCT02998970.

Background Oral anticoagulation (OAC) therapy prevents morbidity and mortality in nonvalvular atrial fibrillation; whether location of diagnosis influences OAC uptake or adherence is unknown. Methods and Results Retrospective cohort study (2008–2019), identifying adults with incident nonvalvular atrial fibrillation across health care settings (emergency department, hospital, outpatient) at high risk of stroke. OAC uptake and adherence via proportion of days covered for direct OACs and time in therapeutic range for warfarin were measured. Proportion of days covered was categorized as low (0–39%), intermediate (40–79%), and high (80–100%). Warfarin control was defined as time in therapeutic range ≥65%. All‐cause mortality was examined at a 3‐year landmark. Among 75 389 patients with nonvalvular atrial fibrillation (47.0% women, mean 77.4 years), 19.7% were diagnosed in the emergency department, 59.1% in the hospital, and 21.2% in the outpatient setting. Ninety‐day OAC uptake was 51.6% in the emergency department, 50.9% in the hospital, and 67.9% in the outpatient setting (P

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 (Pint=0.59) or BARC bleeding (Pint=0.47) nor for sex and genotype (MACE Pint=0.15, and BARC bleeding Pint=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.

A recent acute coronary syndrome provides an opportunity to optimise secondary prevention strategies to reduce the risk of future cardiovascular events. This review provides an updated synopsis of current evidence-based approaches. New clinical trial data on the use of antiplatelet and anticoagulants allow choices of the selection and duration of treatment. Lipid lowering after an acute coronary syndrome is now enhanced, with proprotein convertase subtilisin-kexin type 9 inhibitors providing added benefit on top of statin and ezetimibe treatment in high-risk patients. In addition, a recent trial of icosapent ethyl, a highly purified ethyl ester of eicosapentaenoic acid, addresses residual risk in patients with elevated triglycerides already treated with statins. The use of both sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes reduces cardiovascular events independently of glucose lowering. Résumé: La survenue récente d’un syndrome coronarien aigu offre l’occasion d’optimiser les stratégies de prévention secondaire en vue de réduire le risque d’événements cardiovasculaires futurs. Le présent article de synthèse offre une vue d’ensemble actualisée des approches contemporaines fondées sur des données probantes. Les nouvelles données d’essais cliniques sur l’utilisation d’antiplaquettaires et d’anticoagulants permettent de choisir un traitement et sa durée. La réduction des lipides après la survenue d’un syndrome coronarien aigu se trouve maintenant améliorée, les bienfaits des inhibiteurs de la proprotéine convertase subtilisine/kexine de type 9 s’ajoutant à ceux du traitement par des statines et l’ézétimibe chez les patients à haut risque. En outre, un essai récent portant sur l’icosapent éthyl, un ester éthylique hautement purifié de l’acide eicosapentaénoïque, aborde le risque résiduel chez les patients présentant une hypertriglycéridémie déjà traités par des statines. L’utilisation d’inhibiteurs du cotransporteur sodium-glucose de type 2 et d’agonistes des récepteurs du peptide-1 apparenté au glucagon chez les patients atteints de diabète de type 2 limite les événements cardiovasculaires indépendamment de la diminution de la glycémie.

Objectives: This study will compare the incidence of major adverse cardiovascular events (MACEs) with androgen deprivation therapy (ADT) among men with advanced prostate cancer who are being treated with a gonadotropin-releasing hormone (GnRH) antagonist versus a GnRH agonist. Background: Treatment of advanced prostate cancer with ADT might increase the risk of subsequent cardiovascular events among men with known atherosclerotic cardiovascular disease (ASCVD), but a recent meta-analysis suggested that this risk might be lower with ADT using a GnRH antagonist versus a GnRH agonist. Methods: PRONOUNCE is a multicenter, prospective, randomized, open, blinded endpoint trial that will enroll approximately 900 patients with advanced prostate cancer and pre-existing ASCVD who will be treated with ADT. Participants will be randomized to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide as ADT for 12 months. The primary endpoint is time from randomization to first confirmed, adjudicated occurrence of a MACE, which is defined as a composite of all-cause death, nonfatal myocardial infarction, or nonfatal stroke through 12 months of ADT treatment. Baseline cardiovascular biomarkers (high-sensitivity C-reactive protein, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide), as well as serial inflammatory and immune biomarkers, will be evaluated in exploratory analyses. Results: As of October 1, 2019, a total of 364 patients have been enrolled. The mean age is 74 years, 90% are white, 80% have hypertension or dyslipidemia, 30% diabetes mellitus, 40% have had a previous myocardial infarction, and 65% have had previous revascularization. Regarding prostate cancer features at randomization, 48% of the patients had localized disease, 23% had locally advanced disease, and 18% had metastatic disease. Conclusions: PRONOUNCE is the first prospective cardiovascular outcomes trial in advanced prostate cancer that will delineate whether the risk of subsequent cardiovascular events associated with ADT is lower with a GnRH antagonist versus a GnRH agonist for men with pre-existing ASCVD. (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease [PRONOUNCE]; NCT02663908)

Background: Despite the widespread use of statins, approximately 40% to 50% of Canadian patients with known cardiovascular disease do not achieve the low-density lipoprotein cholesterol (LDL-C) goal. Guidelines Oriented Approach to Lipid lowering (GOAL) is an investigator-initiated study aiming to ascertain the use of second- and third-line therapy and its impact on LDL-C goal achievement in a real-world setting. Methods: GOAL enrolled patients with clinical vascular disease or familial hypercholesterolemia and LDL-C > 2.0 mmol/L despite maximally tolerated statin therapy. During follow-up, physicians managed patients as clinically indicated but with online reminders of guideline recommendations. Results: Of 2009 patients enrolled (median age 63 years, 42% were female), baseline total cholesterol was 5.5 ± 1.4 mmol/L, LDL-C was 3.3 ± 1.3 mmol/L, non–high-density lipoprotein cholesterol was 4.1 ± 1.4 mmol/L, high-density lipoprotein cholesterol was 1.3 ± 0.4 mmol/L, and triglycerides were 2.0 ± 1.5 mmol/L. Lipid-lowering therapy used at baseline was statin therapy in 76% (with 24% statin intolerant) and ezetimibe in 25%. During follow-up, the proportion of patients achieving an LDL-C level of < 2.0 mmol/L increased significantly to 50.8% as a result of additional lipid-lowering therapy. Patients achieving the recommended LDL-C level were more likely to not be statin intolerant (83.8% vs 70.7%, P 2,0 mmol/l malgré un traitement par une statine à la dose maximale tolérée, ont été inscrits à l’étude GOAL. Pendant la période de suivi, les médecins prenaient en charge le traitement de leurs patients selon les besoins cliniques, mais en recevant par voie électronique des rappels des recommandations formulées dans les lignes directrices. Résultats: Chez les 2009 patients inscrits à l’étude (âge médian : 63 ans; femmes : 42 %), les taux initiaux moyens étaient les suivants : cholestérol total initial : 5,5 ± 1,4 mmol/l, C-LDL : 3,3 ± 1,3 mmol/l, C non HDL (autre que le cholestérol à lipoprotéines de haute densité) : 4,1 ± 1,4 mmol/l, C-HDL (des lipoprotéines de haute densité) : 1,3 ± 0,4 mmol/l et triglycérides : 2,0 ± 1,5 mmol/l. Le traitement hypolipidémiant utilisé au début de l’étude était composé d’une statine chez 76 % des participants (24 % des patients ne toléraient pas les statines) et d’ézétimibe chez 25 %. Pendant la période de suivi, la proportion de patients atteignant un taux de C-LDL < 2,0 mmol/l a augmenté de façon significative, jusqu’à atteindre 50,8 %, en raison de l’utilisation d’hypolipidémiants additionnels. Les patients atteignant les taux cibles de C-LDL étaient plus susceptibles de ne pas être intolérants aux statines (83,8 % vs 70,7 %, p < 0,0001) et de prendre un type et une dose de statine hautement efficaces (52,4 % vs 35,9 %, p < 0,0001). Les trois principales raisons évoquées pour expliquer le fait de n’avoir pas eu recours au traitement recommandé par l’ézétimibe étaient le refus du patient (33 %), l’absence de besoin (22 %) et l’intolérance (20 %), alors que dans le cas des inhibiteurs de la PCSK9, les raisons données étaient plutôt le coût élevé (26 %), l’absence de besoin (27 %) et le refus du patient (25 %). Conclusion: Les résultats de cette étude montrent la faisabilité de l’optimisation de la prise en charge, qui entraîne l’atteinte des taux de C-LDL recommandés dans les lignes directrices. Ces résultats pourraient se traduire par des réductions de la morbidité et de la mortalité d’origine cardiovasculaire chez les patients canadiens.

Background In TAILOR‐PCI, genotype‐guided selection of P2Y12 inhibitors after percutaneous coronary intervention did not significantly reduce the risk of ischemic events at 12 months. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD‐GENE) score identifies patients with high platelet reactivity on clopidogrel at increased risk of ischemic events. The aim of this study was to investigate the value of the ABCD‐GENE score for tailoring P2Y12 inhibitor selection after percutaneous coronary intervention. Methods and Results In a post hoc analysis of the TAILOR‐PCI, outcomes were analyzed by ABCD‐GENE score and allocation to genotype‐guided or conventional P2Y12 inhibitor selection. Primary (death, myocardial infarction, or stroke) and secondary (cardiovascular death, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia) outcomes were assessed. Among 3883 patients discharged on clopidogrel in the genotype‐guided and conventional therapy groups, 15.8% and 84.2% had high (≥10 points) or low (

Background Small observational studies have suggested that statin users have a lower risk of dying with COVID‐19. We tested this hypothesis in a large, population‐based cohort of adults in 2 of Canada’s most populous provinces: Ontario and Alberta. Methods and Results We examined reverse transcriptase–polymerase chain reaction swab positivity rates for SARS‐CoV‐2 in adults using statins compared with nonusers. In patients with SARS‐CoV‐2 infection, we compared 30‐day risk of all‐cause emergency department visit, hospitalization, intensive care unit admission, or death in statin users versus nonusers, adjusting for baseline differences in demographics, clinical comorbidities, and prior health care use, as well as propensity for statin use. Between January and June 2020, 2.4% of 226 142 tested individuals aged 18 to 65 years, 2.7% of 88 387 people aged 66 to 75 years, and 4.1% of 154 950 people older than 75 years had a positive reverse transcriptase–polymerase chain reaction swab for SARS‐CoV‐2. Compared with 353 878 nonusers, the 115 871 statin users were more likely to test positive for SARS‐CoV‐2 (3.6% versus 2.8%, P

Background The relationship between health care utilization and outcomes in patients with atrial fibrillation is unknown. The objective of this study was to investigate whether cardiologists’ billing amounts in a fee‐for‐service environment are associated with better patient‐level clinical outcomes. Methods and Results A retrospective cohort study was conducted using administrative claims data of cardiologists in Ontario, Canada between April 1, 2011 and March 31, 2016. The cardiologists were stratified into quintiles based on their median billing patterns per patient over the observation period. The primary outcomes were patient‐level receipt of repeat visits, cardiac diagnostic tests, and medications ≤1 year of index date. The secondary clinical outcomes were death, emergency department visits, and all‐cause hospitalization 1‐year post‐index visit. The patient cohort comprised 182 572 patients with atrial fibrillation (median age 74 years, 58% male) from 467 cardiologists. Patients with atrial fibrillation seen by higher‐billing cardiologists were 26% more likely to have an echocardiogram (adjusted odds ratio [aOR], 1.26 [95% CI, 1.10–1.43] for quintile 5 versus 2), 28% a stress test (aOR, 1.28 [1.12–1.46] for quintile 5 versus 2), 25% continuous electrocardiographic monitoring (aOR, 1.25 [1.08–1.46] for quintile 4 versus 2), and 79% more likely to get a stress echocardiogram (aOR, 1.79 [1.32–2.42] for quintile 5 versus 2). They also had a higher rate of all‐cause hospitalization (aOR, 1.13 [1.07–1.20]). Mortality rates were similar across cardiologists billing quintiles (eg, aOR, 0.98 [0.87–1.11] for quintile 4 versus 2). Conclusions Higher‐billing cardiologists ordered more diagnostic tests per patient with atrial fibrillation but these are not associated with improvements in outcomes.

Introduction: The efficacy and safety of switching P2Y12 receptor antagonists in patients admitted for acute coronary syndrome (ACS) remain unclear. We assessed the short-term clinical outcomes (in-hospital and within 30 days) of switching P2Y12 inhibitor (P2Y12I) drugs versus maintaining the same regimen by performing a comprehensive review and meta-analysis of available data. Methods: MEDLINE/PubMed/SCOPUS/Cochrane databases were screened for studies regarding switching of P2Y12I in patients with ACS that reported 30 days follow-up. Major cardiac events (MACE) and bleeding were compared between patients who were switched/not switched. Results: 22,500 patients from 14 studies were included. Unstable angina/non-ST elevation myocardial infarction (62.0%, interquartile range, 52.8%–68.0%) was the most common clinical presentation. The total number switched was 4294 (19.1%); escalation in 3416 (79.5%) patients (from clopidogrel to prasugrel, 62.9%) and de-escalation in 18.5%. Pooled analysis revealed no significant differences in MACE for any comparison; risk of bleeding was significantly increased among switched patients overall (odds ratio [OR], 1.60; 95% confidence interval [CI] 1.22–2.10) and increased in the escalation group (OR, 1.51; 95% CI, 1.06–2.16). Conclusions: Among patients presenting with ACS, switching from one P2Y12I agent to another in the acute phase seems associated with a short-term increased risk of bleeding. Accurate upfront selection and prescription of a P2Y12I based on ischemic and bleeding risks is paramount to avoid adverse events switching-related during hospitalization and in the first 30 days. Keywords: Novel P2Y12 inhibitors, Switching, Clopidogrel, Ticagrelor, Prasugrel, Acute coronary syndrome

Background We sought to determine temporal trends in use of evidence‐based therapies and clinical outcomes among myocardial infarction (MI) patients with chronic kidney disease (CKD). Methods and Results MI patients from the NCDR (National Cardiovascular Data Registry) Chest Pain–MI Registry between January 2007 and December 2015 were categorized into 3 groups by degree of CKD (end‐stage renal disease on dialysis, CKD [glomerular filtration rate

Background In the EXSCEL (Exenatide Study of Cardiovascular Event Lowering), exenatide once‐weekly resulted in a nonsignificant reduction in major adverse cardiovascular events (MACEs) and a nominal 14% reduction in all‐cause mortality in 14 752 patients with type 2 diabetes mellitus (T2DM) with and without cardiovascular disease. Whether patients at increased risk for events experienced a comparatively greater treatment benefit with exenatide is unknown. Methods and Results In the EXSCEL population, we created risk scores for MACEs and all‐cause mortality using step‐wise selection of baseline characteristics. A risk score was calculated for each patient, and a time‐to‐event model for each end point was developed including the risk score, treatment assignment, and risk‐treatment interaction. Interaction P values evaluating for a differential treatment effect by baseline risk were reported. Over a median follow‐up of 3.2 years (interquartile range, 2.2, 4.4), 1091 (7.4%) patients died and 1744 (11.8%) experienced a MACE. Independent predictors of MACEs and all‐cause mortality included age, sex, comorbidities (eg, previous cardiovascular event), body mass index, blood pressure, hemoglobin A1c, and estimated glomerular filtration rate. The all‐cause mortality and MACE risk models had modest discrimination with optimism‐corrected c‐indices of 0.73 and 0.71, respectively. No interaction was observed between treatment effect and risk profile for either end point (both interactions, P>0.1). Conclusions Baseline characteristics (eg, age, previous cardiovascular events) and routine laboratory values (eg, hemoglobin A1c, estimated glomerular filtration rate) provided modest prognostic value for mortality and MACEs in a broad population of patients with type 2 diabetes mellitus. Exenatide's effects on mortality and MACEs were consistent across the spectrum of baseline risk. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01144338.

Background Little is known about the prognostic implications of frailty, a state of susceptibility to stressors and poor recovery to homeostasis in older people, after myocardial infarction (MI). Methods and Results We studied 3944 MI patients aged ≥65 years treated at 41 Australian hospitals from 2009 to 2016 in the CONCORDANCE (Australian Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events) registry. Frailty index (FI) was determined using the health deficit accumulation method. All‐cause and cardiac‐specific mortality at 6 months were compared between frail (FI >0.25) and nonfrail (FI ≤0.25) patients. Among 1275 patients with ST‐segment–elevation MI (STEMI), 192 (15%) were frail, and among 2669 non‐STEMI (NSTEMI) patients, 902 (34%) were frail. Compared with nonfrail counterparts, frail STEMI patients received 30% less reperfusion therapy and 22% less revascularization during index hospitalization; frail NSTEMI patients received 30% less diagnostic angiography and 39% less revascularization. Unadjusted 6‐month all‐cause mortality (STEMI: 13% versus 3%; NSTEMI: 13% versus 4%) and cardiac‐specific mortality (STEMI: 6% versus 1.4%, NSTEMI: 3.2% versus 1.2%) were higher among frail patients. After adjustment for known prognosticators, FI was significantly associated with higher 6‐month all‐cause (STEMI: odds ratio: 1.74 per 0.1 FI [95% confidence interval, 1.37–2.22], P

BackgroundWomen hospitalized with a non‐ST segment elevation acute coronary syndrome (ACS) have worse clinical outcomes compared with men. An early invasive strategy with prompt coronary revascularization may mitigate sex differences in outcomes. However, few contemporary studies have evaluated whether clinical outcomes differ between women and men presenting with ACS treated with an early invasive strategy. Methods and ResultsA population‐based cohort of hospitalized ACS patients who received prompt cardiac catheterization from 2008 to 2011 in Ontario, Canada and followed for up to 2 years was studied. Clinical outcomes were compared between men and women, stratified by the use of coronary revascularization. Inverse probability weighting using the propensity score accounted for measured differences in baseline characteristics between men and women. Among the 23 473 ACS patients who received cardiac catheterization during an index hospitalization, 66.1% of men and 51.8% of women received coronary revascularization during the same hospitalization. In the propensity‐weighted cohort of patients who received coronary revascularization, the 1‐year rate of death or recurrent ACS was 10.6% for men (referent) compared with 13.1% for women (hazard ratio 1.24; 95% CI 1.16–1.33). In contrast, outcomes for patients who did not receive coronary revascularization did not differ significantly between women and men at 1 year (17.8% versus 16.9%; hazard ratio 1.06; 95% CI 0.99–1.14) or at longer follow‐up. ConclusionsAn increased risk of adverse clinical outcomes was observed for women with ACS undergoing an early invasive strategy and coronary revascularization compared with men.

Introduction For non-ST-segment elevation acute coronary syndrome (NSTEACS) there is a gap between the use of class I guideline recommended therapies and clinical practice. The Global Registry of Acute Coronary Events (GRACE) risk score is recommended in international guidelines for the risk stratification of NSTEACS, but its impact on adherence to guideline-indicated treatments and reducing adverse clinical outcomes is unknown. The objective of the UK GRACE Risk Score Intervention Study (UKGRIS) trial is to assess the effectiveness of the GRACE risk score tool and associated treatment recommendations on the use of guideline-indicated care and clinical outcomes.Methods and analysis The UKGRIS, a parallel-group cluster randomised registry-based controlled trial, will allocate hospitals in a 1:1 ratio to manage NSTEACS by standard care or according to the GRACE risk score and associated international guidelines. UKGRIS will recruit a minimum of 3000 patients from at least 30 English National Health Service hospitals and collect healthcare data from national electronic health records. The co-primary endpoints are the use of guideline-indicated therapies, and the composite of cardiovascular death, non-fatal myocardial infarction, new onset heart failure hospitalisation or cardiovascular readmission at 12 months. Secondary endpoints include duration of inpatient hospital stay over 12 months, EQ-5D-5L responses and utilities, unscheduled revascularisation and the components of the composite endpoint over 12 months follow-up.Ethics and dissemination The study has ethical approval (North East - Tyne & Wear South Research Ethics Committee reference: 14/NE/1180). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the funder’s open access policy.Trial registration number ISRCTN29731761; Pre-results.