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Background and Aims: The evidence for beta-blocker therapy after myocardial infarction (MI) is randomized trials conducted more than 30 years ago, and the continued efficacy has been questioned., Design and Methods: The ongoing Danish (DANBLOCK) and Norwegian (BETAMI) randomized beta-blocker trials are joined to evaluate the effectiveness and risks of long-term beta-blocker therapy after MI. Patients with normal or mildly reduced left ventricular ejection fraction (LVEF ≥ 40%) will be randomized to open-label treatment with beta-blockers or no such therapy. The event-driven trial will randomize ∼5700 patients and continue until 950 primary endpoints have occurred. As of July 2023, 5228 patients have been randomized. Of the first 4000 patients randomized, median age was 62 years, 79% were men, 48% had a ST-segment elevation myocardial infarction (STEMI), and 84% had a normal LVEF. The primary endpoint is a composite of adjudicated recurrent MI, incident heart failure (HF), coronary revascularization, ischaemic stroke, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest. The primary safety endpoint includes a composite of recurrent MI, HF, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest 30 days after randomization. Secondary endpoints include each of the components of the primary endpoint, patient-reported outcomes, and other clinical outcomes linked to beta-blocker therapy. The primary analysis will be conducted according to the intention-to-treat principle using a Cox proportional hazards regression model. End of follow-up is expected in December 2024., Conclusion: The combined BETAMI-DANBLOCK trial will have the potential to affect current clinical practice for beta-blocker therapy in patients with normal or mildly reduced LVEF after MI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Guidelines concerning β-blocker treatment following acute myocardial infarction (AMI) are based on studies undertaken before the implementation of reperfusion and secondary prevention therapies. We aimed to estimate the effect of oral β-blockers on mortality in contemporary post-AMI patients with low prevalence of heart failure and/or reduced left ventricular ejection fraction., Methods and Results: A random effects model was used to synthetize results of 16 observational studies published between 1 January 2000 and 30 October 2017. Publication bias was evaluated, and heterogeneity between studies examined by subgroup and random effects meta-regression analyses considering patient-related and study-level variables. The pooled estimate showed that β-blocker treatment [among 164 408 (86.8%) patients, with median follow-up time of 2.7 years] was associated with a 26% reduction in all-cause mortality [rate ratio (RR) 0.74, 95% confidence interval (CI) 0.64-0.85] with moderate heterogeneity (I2 = 67.4%). The patient-level variable mean age of the cohort explained 31.5% of between study heterogeneity. There was presence of publication bias, or small study effect, and when controlling for bias by the trim and fill simulation method, the effect disappeared (adjusted RR 0.90, 95% CI 0.77-1.04). Also, small study effect was demonstrated by a cumulative meta-analysis starting with the largest study showing no effect, with increasing effect as the smaller studies were accumulated., Conclusion: Evidence from this study suggests that there is no association between β-blockers and all-cause mortality. A possible beneficial effect in AMI survivors needs to be tested by large randomized clinical trials.

Background In contemporary atrial fibrillation trials most deaths are cardiac related, whereas stroke and bleeding represent only a small subset of deaths. We aimed to evaluate the long-term risk of cardiac events and all-cause mortality in individuals with atrial fibrillation compared to no atrial fibrillation. Design A systematic review and meta-analysis of studies published between 1 January 2006 and 21 October 2016. Methods Four databases were searched. Studies had follow-up of at least 500 stable patients for either cardiac endpoints or all-cause mortality for 12 months or longer. Publication bias was evaluated and random effects models were used to synthesise the results. Heterogeneity between studies was examined by subgroup and meta-regression analyses. Results A total of 15 cohort studies was included. Analyses indicated that atrial fibrillation was associated with an increased risk of myocardial infarction (relative risk (RR) 1.54, 95% confidence interval (CI) 1.26-1.85), all-cause mortality (RR 1.95, 95% CI 1.50-2.54) and heart failure (RR 4.62, 95% CI 3.13-6.83). Coronary heart disease at baseline was associated with a reduced risk of myocardial infarction and explained 57% of the heterogeneity. A prospective cohort design accounted for 25% of all-cause mortality heterogeneity. Due to there being fewer than 10 studies, sources of heterogeneity were inconclusive for heart failure. Conclusions Atrial fibrillation seems to be associated with an increased risk of subsequent myocardial infarction in patients without coronary heart disease and an increased risk of, all-cause mortality and heart failure in patients with and without coronary heart disease.