Discontinuation of β-blockers in stable patients with previous myocardial infarction, preserved left ventricular ejection fraction, and no heart failure: a pooled analysis of individual patient data.

Abstract (English)

BACKGROUND: Many stable patients with chronic coronary syndrome continue β-blocker therapy for years after a myocardial infarction, despite having no clear ongoing indication. Whether β-blockers can be safely discontinued in such patients remains uncertain. The objective of this analysis was to assess the non-inferiority of β-blocker discontinuation versus continuation in patients with previous myocardial infarction and no remaining indication. METHODS: We performed a pooled analysis of individual patient data from the ABYSS and SMART-DECISION randomised trials in stable patients over 6 months after a myocardial infarction with a left ventricular ejection fraction of ≥40% and no heart failure. Non-inferiority was assessed for the composite primary endpoint of all-cause death, myocardial infarction, stroke, or hospitalisation for cardiovascular reasons, and for the key secondary endpoint of all-cause death, myocardial infarction, or hospitalisation for heart failure. Analyses used a one-stage mixed-effects Cox proportional hazards model including trial as a random effect with margins of 1·25 for the primary endpoint and 1·40 for the key secondary endpoint. The review protocol was registered with PROSPERO, number CRD420261299839. FINDINGS: Among 6238 patients (3698 from ABYSS and 2540 from SMART-DECISION), 3092 were assigned to β-blocker discontinuation and 3146 to continuation. Median time from index myocardial infarction to randomisation was 3·6 years (IQR 1·6-7·5) and median follow-up was 3·0 years (2·3-3·8). The primary endpoint occurred in 532 (17·2%) of 3092 patients in the β-blocker discontinuation group and 500 (15·9%) of 3146 in the continuation group (hazard ratio 1·09 [95% CI 0·97-1·24]; p_{non-inferiority}=0·016). The key secondary endpoint occurred in 201 (6·5%) of 3092 patients in the discontinuation group and 201 (6·4%) of 3146 patients in the continuation group (1·01 [0·83-1·23]; p_{non-inferiority}=0·0006). Findings were consistent irrespective of background left ventricular ejection fraction. INTERPRETATION: In stable patients with previous myocardial infarction, left ventricular ejection fraction ≥40%, no heart failure, and no other indication for β-blocker therapy, discontinuation met the non-inferiority criteria for the primary and key secondary endpoints. Interpretation of the primary endpoint is limited by its hospitalisation-heavy and trial-dependent composition. FUNDING: None.