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There is strong evidence supporting the benefits of beta-blockers in patients with heart failure and reduced ejection fraction. Additionally, prospective, randomized studies have demonstrated that long-term treatment with beta-blockers improves outcomes in patients after myocardial infarction (MI) and reduces mortality by approximately 20%. However, most of these studies typically involve patients who have experienced large myocardial infarctions and have widespread left ventricular systolic dysfunction. Furthermore, many of these studies were conducted before the widespread use of high-sensitivity troponins, percutaneous coronary interventions, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists. Long-term beta-blocker therapy in patients who have had an acute myocardial infarction and preserved systolic left ventricular function has not been adequately investigated in sufficiently robust, randomized clinical trials.

The study evaluated whether long-term oral beta-blocker use in patients who have had an acute myocardial infarction (AMI) and preserved left ventricular ejection fraction reduces the composite endpoint of all-cause mortality or recurrent myocardial infarction.

The REDUCE-AMI study is a registry-based, randomized, parallel-group, open-label, multicenter trial conducted across 38 centers in Sweden, 1 center in Estonia, and 6 centers in New Zealand. Approximately 5000 patients who experienced acute myocardial infarction and underwent coronary angiography with an ejection fraction (EF) ? 50% were randomized in a 1:1 ratio to receive either oral metoprolol or bisoprolol titrated to a target dose of ?100 mg/day or ?5 mg/day, respectively (n = 2,508), or standard care (n = 2,512). The primary endpoint is the composite of all-cause mortality or new non-fatal myocardial infarction. Several secondary endpoints include all-cause mortality, cardiovascular mortality, new myocardial infarction, rehospitalization due to heart failure and atrial fibrillation, symptoms, functional status, and health-related quality of life. Safety endpoints include bradycardia, AV block II-III, hypotension, syncope or need for pacemaker, asthma or chronic obstructive pulmonary disease exacerbation, and stroke.

In the REDUCE-MI study, 2508 patients were included in the beta-blocker arm, while 2512 patients were included in the standard care arm. The primary endpoint occurred in 7.9% of patients in the beta-blocker arm and 8.3% of patients in the standard care arm (95% CI 0.79-1.16, p=0.64). When each component of the primary endpoint was analyzed separately, there was no statistically significant difference between the two groups. Furthermore, all-cause mortality occurred in 3.9% and 4.1% of patients in the beta-blocker and standard care arms, respectively, while new myocardial infarction occurred in 4.5% and 4.7% of patients, and hospitalization due to heart failure occurred in 0.8% and 0.9% of patients, respectively. There were no statistically significant differences between the two groups for any of these outcomes.

The REDUCE-AMI study showed that beta-blocker therapy with metoprolol or bisoprolol in patients with preserved ejection fraction after acute myocardial infarction was not associated with a reduced risk of all-cause mortality or new myocardial infarction when compared to standard care.

REDUCE-AMI provides the first modern, randomized data on beta-blocker therapy and demonstrates that it is not associated with reduced all-cause mortality or recurrent myocardial infarction. There was a significant crossover between groups at one year, and medication adherence could not be evaluated thereafter. This, combined with a slightly lower event rate than expected, may have influenced the outcomes in longer-term follow-up.

Over time, the increased use of beta-blockers in the usual care group may reflect the treatment of common comorbidities seen after AMI, such as stable angina, atrial fibrillation, hypertension, or subsequent reduced left ventricular ejection fraction. Evaluation of endpoints was limited to data collected from registries, which constrained the assessment of associated cardiovascular events in this cohort. Therefore, patients with preserved left ventricular ejection fraction after AMI may not derive significant cardiac benefit from beta-blockers unless there is another indication for their use.