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

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 left ventricular ejection fraction (LVEF) ≥40%. METHODS AND RESULTS: In a multicentre prospective real-world cohort (n = 3762) of patients hospitalized for ACS, patients with LVEF ≥40% and beta-blockers at discharge were included. Patients who continued beta-blockers at 1 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 4-year follow-up. The primary endpoint was major adverse cardiovascular events (MACE), a composite of 4-year cardiovascular death, myocardial infarction, stroke, transient ischaemic attack, unplanned coronary revascularization, or unstable angina hospitalization. Of 2077 patients, 1758 (85%) continued beta-blockers and 319 (15%) had discontinued beta-blockers at 1 year. The risk of the primary endpoint was similar in both groups [14.1 vs. 14.3% with beta-blocker discontinuation vs. 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 with NSTEMI [aHR = 0.70 (0.40-1.22), Pinteraction = 0.033], whereas there was no interaction with LVEF (Pinteraction = 0.68). CONCLUSION: Beta-blocker discontinuation within 12 months following ACS with LVEF ≥40% was not associated with an increased risk of MACE compared with 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.