Safety of beta-blocker discontinuation after acute coronary syndromes with preserved or mildly reduced left ventricular ejection fraction: a target trial emulation from a real-world cohort

Eur J Prev Cardiol. 2024 Oct 26:zwae346. doi: 10.1093/eurjpc/zwae346. Online ahead of print.

Abstract

Aims: The benefit of long-term beta-blocker therapy after acute coronary syndromes (ACS) without heart failure in the reperfusion era is uncertain. Two recent randomized trials found conflicting results. The present study assessed the safety of beta-blocker discontinuation within 12 months following ACS with LVEF ≥40%.

Methods: In a multicentre prospective real-world cohort (N=3,762) of patients hospitalized for ACS, patients with LVEF ≥40% and beta-blockers at discharge were included. Patients who continued beta-blockers at one year were compared with those who discontinued beta-blockers within 12 months post-ACS using target trial emulation and inverse probability weighting over an additional four-year follow-up. The primary endpoint was major adverse cardiovascular events (MACE), a composite of four-year cardiovascular death, myocardial infarction, stroke, transient ischemic attack, unplanned coronary revascularization, or unstable angina hospitalization.

Results: Of 2,077 patients, 1,758 (85%) continued beta-blockers and 319 (15%) had discontinued beta-blockers at one year. The risk of primary endpoint was similar in both groups (14.1% versus 14.3% with beta-blocker discontinuation versus continuation; adjusted hazard ratio [aHR]=0.98; 95% confidence interval, 0.72-1.34, P=0.91). Subgroup analysis suggested a higher risk of primary endpoint with beta-blocker discontinuation after STEMI (aHR=1.46 [0.99-2.16]) compared to NSTEMI (aHR=0.70 [0.40-1.22], Pinteraction=0.033), whereas there was no interaction with LVEF (Pinteraction=0.68).

Conclusions: Beta-blocker discontinuation within 12 months following ACS with LVEF ≥40% was not associated with an increased risk of MACE compared to long-term beta-blocker therapy. Subgroup analysis suggested potential risk in STEMI patients. Discontinuing beta-blockers 12 months after ACS appears safe in patients with LVEF ≥40%, particularly after NSTEMI.

Keywords: NSTEMI; STEMI; acute coronary syndrome; beta-blocker; mildly reduced ejection fraction; myocardial infarction; preserved ejection fraction; rehabilitation; secondary prevention.

Plain language summary

Beta-blockers are part of the standard drug therapy prescribed to prevent adverse health events in patients who suffered from myocardial infarction. However, the studies that established their benefit were conducted before the advent of modern therapies, that have since then dramatically changed the prognosis. The benefit of long-term beta-blockers in the contemporary era has therefore been questioned. The present study assessed the safety of beta-blocker discontinuation within 12 months after myocardial infarction in patients who did not have severely impaired heart function. Beta-blocker discontinuation within 12 months after myocardial infarction was safe, as it was not associated with a higher risk of major adverse cardiovascular events or death, compared to long-term beta-blocker continuation. Patients who presented with acute occlusion of a coronary artery – a severe type of myocardial infarction referred to as “ST-elevation myocardial infarction” – may still benefit from long-term beta-blocker therapy based on subgroup analysis.