Discontinuation of long-term beta-blockers in post-MI patients with LVEF ≥40% does not change clinical outcomes

In SMART-DECISION among stable patients with LVEF ≥40% and no HF receiving beta-blockers for ≥1 year after MI, discontinuation of this therapy was noninferior to continuation regarding the composite outcome of all-cause mortality, recurrent MI, or HF hospitalization.

This summary is based on the publication of Choi KH, Kang D, Kim W, et al. - Discontinuation of Beta-Blocker Therapy after Myocardial Infarction. N Engl J Med. 2026 Apr 2;394(13):1302-1312. doi: 10.1056/NEJMoa2601005

Introduction and methods

Background

After an acute MI, many patients are treated with beta-blockers for years [1,2]. However, the treatment effects of prolonged beta-blocker therapy may vary depending on LV function [3-8].

Aim of the study

The study aim was to determine whether discontinuation of long-term beta-blocker therapy is noninferior to beta-blocker continuation with regard to major clinical outcomes in patients who are in stable condition after an MI and do not have LV systolic dysfunction or HF.

Methods

The SMART-DECISION (SMart Angioplasty Research Team: DEcision on Medical Therapy in Patients with Coronary Artery DIsease or Structural Heart Disease Undergoing InterventiON) trial was a multicenter, open-label, noninferiority, phase 4 RCT conducted in South Korea. The researchers randomized 2540 stable post-MI patients with LVEF ≥40% and no HF who had received beta-blockers for ≥1 year after the MI to discontinue or continue beta-blocker therapy. Median time from index MI to randomization was 4.7 years (IQR: 2.4–8.4), and median follow-up duration was 3.1 years (IQR: 2.5–3.5).

Outcomes

The primary endpoint was an adjudicated composite outcome of all-cause mortality, recurrent MI, or HF hospitalization. Key secondary endpoints included the individual components of the primary endpoint, CV death, LVEF change, and quality of life assessed with the 29-item Patient-Reported Outcomes Measurement Information System.

Main results

• During follow-up, the primary endpoint occurred in 58 of 1246 patients (4-year Kaplan–Meier estimate: 7.2%) in the beta-blocker discontinuation group and 74 of 1294 patients (4-year Kaplan–Meier estimate: 9.0%) in the continuation group (risk difference: −1.8 percentage points; 95%CI: −5.5 to 1.9; HR: 0.80; 95%CI: 0.57–1.13). This met the prespecified noninferiority margin for the upper limit of the 95%CI of 1.4 (P=0.001 for noninferiority).
• As for key secondary endpoints, the 4-year Kaplan–Meier estimates in the discontinuation and continuation groups were:
  • for all-cause mortality: 2.4% versus 3.4% (HR: 0.71; 95%CI: 0.43–1.16);
  • for recurrent MI: 2.3% versus 2.6% (HR: 1.11; 95%CI: 0.63–1.96);
  • for HF hospitalization: 2.2% versus 2.1% (HR: 0.82; 95%CI: 0.42–1.57).
• Subgroup analysis showed generally consistent results across subgroups stratified by, among others, age, sex, or LVEF.
• The frequency of serious adverse events was similar in the discontinuation and continuation groups (11.5% vs. 13.4%), as was the incidence of serious cardiac events occurred (5.7% vs. 6.1%).

Conclusion

In the SMART-DECISION trial among stable post-MI patients with LVEF ≥40% and no HF who were treated with beta-blockers for ≥1 year, discontinuation of beta-blocker therapy was noninferior to continued therapy with regard to the composite outcome of all-cause mortality, recurrent MI, or HF hospitalization.

The authors refer extensively to the previously reported results of the French ABYSS (Assessment of Beta-Blocker Interruption 1 Year after an Uncomplicated Myocardial Infarction on Safety and Symptomatic Cardiac Events Requiring Hospitalization) trial, in which interruption of long-term beta-blocker therapy after an MI was compared with treatment continuation [9]. It did not show noninferiority of beta-blocker interruption, but according to Choi et al. “[t[he apparent discrepancy in results between the ABYSS and SMART-DECISION trials may be explained by key differences in trial design and clinical context.”

Find this article online at N Engl J Med.

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