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.

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.