Benefit-risk of colchicine and spironolactone in acute myocardial infarction: a prespecified generalised pairwise comparisons analysis of the CLEAR trial.

Background: Composite outcomes in cardiovascular trials often group events of unequal clinical importance, and conventional analyses may obscure treatment trade-offs. Generalised pairwise comparisons (GPC), expressed as a win ratio (WR), allow for hierarchical ranking of events and incorporation of recurrent outcomes, providing a potentially more intuitive assessment of benefit-risk.

Methods: In a prespecified exploratory analysis of the 2×2 factorial, randomised CLEAR (Colchicine and Spironolactone in Patients with Myocardial Infarction) trial (7062 patients within 72 hours of acute myocardial infarction (MI) and percutaneous coronary intervention), we applied both time-to-first and recurrent-event GPC to reassess low-dose colchicine (0.

Spironolactone versus placebo in patients undergoing maintenance dialysis (ACHIEVE): an international, parallel-group, randomised controlled trial.

Background: Patients undergoing maintenance dialysis for kidney failure are at substantial risk of cardiovascular morbidity and mortality. We aimed to establish if spironolactone reduces heart failure and cardiovascular deaths in these patients.

Methods: ACHIEVE was an international, parallel-group, randomised controlled trial done in 143 dialysis programmes in 12 countries.

Training the next generation of clinical trial biostatisticians.

BackgroundThere is a critical shortage of biostatistics expertise and targeted training programs in clinical trials across Canada.MethodsThe Canadian Network for Statistical Training in Trials (CANSTAT), a pan-Canadian, multi-institutional training platform for biostatisticians in clinical trials, was developed to increase clinical trial biostatistics capacity in Canada.ResultsCANSTAT's training program integrates experiential learning through mentorship and placements at clinical trial sites, online workshops, and capacity-building meetings.

Can a Combined Epigenetic-Biomarker Score Supplant Chronologic Age as an Independent Determinant of Incident Death in Adults with Dysglycemia.

Background: Diabetes and prediabetes are associated with premature death and are recognized as conditions of accelerated biologic aging. To date, the best measurement of biologic age is chronologic age. Measures of biologic age that can replace chronologic age as a predictor of death can better approximate risk in affected individuals.

Comparison of total event analysis and first event analysis in relation to heterogeneity in cardiovascular trials.

Background: In cardiovascular (CV) trials, analyzing the total number of events, rather than just time-to-first event, enhances understanding of participants' health. Adapting Cox models to account for between-subject heterogeneity in multiple events and understanding its impact plays crucial roles in total event analysis.

Method: This study compares effect sizes from first event and total event analyses in three cardiovascular trials: ORIGIN (N = 12,537, median follow-up of 6.

The Aldosterone Blockade for Health Improvement Evaluation in End-Stage Renal Disease (ACHIEVE) Trial: Rationale and Clinical Research Protocol.

Background: The mineralocorticoid aldosterone may contribute to the risk of cardiovascular morbidity and mortality in patients receiving maintenance dialysis. Whether spironolactone, a mineralocorticoid receptor antagonist, improves outcomes for patients receiving maintenance dialysis is unclear.

Objective: To assess the efficacy and safety of spironolactone in patients receiving maintenance dialysis.

Statistical Methods for Analyzing EQ-5D in Randomized Clinical Trials: A Systematic Literature Review.

Objectives: We conducted a systematic literature review to summarize the application of statistical methods for analyzing treatment effect on EQ-5D in randomized clinical trials (RCTs).

Method: We searched 2 electronic databases (MEDLINE and EMBASE, from inception through 2021) and www.

Clinicaltrial: gov.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium: A Cluster Randomized Crossover Trial.

Importance: Delirium is common after cardiac surgery and associated with adverse outcomes. Intraoperative benzodiazepines may increase postoperative delirium but restricting intraoperative benzodiazepines has not yet been evaluated in a randomized trial.

Objective: To determine whether an institutional policy of restricted intraoperative benzodiazepine administration reduced the incidence of postoperative delirium.

Comparative performance of risk prediction indices for mortality or readmission following heart failure hospitalization.

Aims: Risk prediction indices used in worsening heart failure (HF) vary in complexity, performance, and the type of datasets in which they were validated. We compared the performance of seven risk prediction indices in a contemporary cohort of patients hospitalized for HF.

Methods And Results: We assessed the performance of the Length of stay and number of Emergency department visits in the prior 6 months (LE), Length of stay, number of Emergency department visits in the prior 6 months, and admission N-Terminal prohormone of brain natriuretic peptide (NT-proBNP (LENT), Length of stay, Acuity, Charlson co-morbidity index, and number of Emergency department visits in the prior 6 months (LACE), Get With The Guidelines Heart Failure (GWTG), Readmission Risk Score (RRS), Enhanced Feedback for Effective Cardiac Treatment model (EFFECT), and Acute Decompensated Heart Failure National Registry (ADHERE) risk indices among consecutive patients hospitalized for HF and discharged alive from January 2017 to December 2019 in a network of hospitals in England.

Routine Spironolactone in Acute Myocardial Infarction.

Background: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain.

Methods: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo.

Long-term clinical outcomes and healthcare resource utilization in male and female patients following hospitalization for heart failure.

Aims: Heart failure (HF) is a leading cause of hospitalization, and sex differences in care have been described. We assessed sex-specific clinical outcomes and healthcare resource utilization following hospitalization for HF.

Methods And Results: This was an exploratory analysis of patients hospitalized for HF across 10 Canadian hospitals in the Patient-Centered Care Transitions in HF (PACT-HF) cluster-randomized trial.

Improving analysis of cognitive outcomes in cardiovascular trials using different statistical approaches.

Background: The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) questionnaires are commonly used to measure global cognition in clinical trials. Because these scales are discrete and bounded with ceiling and floor effects and highly skewed, their analysis as continuous outcomes presents challenges. Normality assumptions of linear regression models are usually violated, which may result in failure to detect associations with variables of interest.

Risk of Stroke or Systemic Embolism According to Baseline Frequency and Duration of Subclinical Atrial Fibrillation: Insights From the ARTESiA Trial.

Background: In the ARTESiA trial (Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation), apixaban, compared with aspirin, reduced stroke or systemic embolism in patients with device-detected subclinical atrial fibrillation (SCAF). Clinical guidelines recommend considering SCAF episode duration when deciding whether to prescribe oral anticoagulation for this population.

Methods: We performed a retrospective cohort study in ARTESiA.

Anticoagulation in device-detected atrial fibrillation with or without vascular disease: a combined analysis of the NOAH-AFNET 6 and ARTESiA trials.

Background And Aims: The optimal antithrombotic therapy in patients with device-detected atrial fibrillation (DDAF) is unknown. Concomitant vascular disease can modify the benefits and risks of anticoagulation.

Methods: These pre-specified analyses of the NOAH-AFNET 6 (n = 2534 patients) and ARTESiA (n = 4012 patients) trials compared anticoagulation with no anticoagulation in patients with DDAF with or without vascular disease, defined as prior stroke/transient ischaemic attack, coronary or peripheral artery disease.

Secondary Conduits in Coronary Artery Bypass Grafting Surgery.

Background: Recent evidence has suggested use of the right internal mammary artery (RIMA) is associated with worse clinical outcomes in patients undergoing coronary artery bypass grafting (CABG) surgery. Therefore, we compared the clinical consequences of secondary conduit selection (RIMA vs radial artery vs saphenous vein) after CABG.

Methods: A post-hoc analysis of the CABG Off or On Pump Revascularization Study, involving 3913 patients from 79 centers in 19 countries who underwent CABG surgery and received arterial grafting with at least 2 grafts.

SYNERGY-Everolimus-Eluting Stent With a Bioabsorbable Polymer in ST-Elevation Myocardial Infarction: CLEAR SYNERGY OASIS-9 Registry.

Our objective was to evaluate the clinical effectiveness of the SYNERGY stent (Boston Scientific Corporation, Marlborough, Massachusetts) in patients with ST-elevation myocardial infarction (STEMI). The only drug-eluting stent approved for treatment of STEMI by the Food and Drug Administration is the Taxus stent (Boston Scientific) which is no longer commercially available, so further data are needed. The CLEAR (Colchicine and spironolactone in patients with myocardial infarction) SYNERGY stent registry was embedded into a larger randomized trial of patients with STEMI (n = 7,000), comparing colchicine versus placebo and spironolactone versus placebo.

Effect of a transitional care model following hospitalization for heart failure: 3-year outcomes of the Patient-Centered Care Transitions in Heart Failure (PACT-HF) randomized controlled trial.

Aims: Patients are at high risk of death or readmission following hospitalization for heart failure (HF). We tested the effect of a transitional care model that included month-long nurse-led home visits and long-term heart function clinic visits - with services titrated to estimated risk of clinical events - on 3-year outcomes following hospitalization.

Methods And Results: In a pragmatic, stepped-wedge cluster randomized trial, 10 hospitals were randomized to the intervention versus usual care.

Cognitive performance following stroke, transient ischaemic attack, myocardial infarction, and hospitalisation: an individual participant data meta-analysis of six randomised controlled trials.

Background: Survivors of stroke are often concerned about cognitive problems, and information on the risk of cognitive problems often comes from small studies. We aimed to estimate years of cognitive ageing associated with stroke compared with transient ischaemic attack, myocardial infarction, and other hospitalisations in a large population.

Methods: Using data from six randomised controlled trials (ORIGIN, ONTARGET, TRANSCEND, COMPASS, HOPE-3, and NAVIGATE ESUS), we completed an individual participant data meta-analysis using data requested from the Public Health Research Institute to estimate the association of stroke (by type and severity), transient ischaemic attack, myocardial infarction, and other hospitalisations with cognitive performance measured at the end of each trial.

Sex hormone-binding globulin and heart failure hospitalizations in patients with dysglycemia: Experiences from the outcome reduction with an Initial Glargine Intervention trial.

Introduction: Sex hormone-binding globulin (SHBG), which binds most of circulating testosterone in blood, has been linked to dysglycemia and cardiovascular disease but the relationship with heart failure remains unclear.

Aim: To study the relation between SHBG and heart failure hospitalizations.

Methods: SHBG levels were analysed in dysglycemic participants at high cardiovascular risk (n = 8401) followed for a median of 6.