Current guidelines regarding beta-blocker use after myocardial infarction (MI) recommend against continuation to improve outcomes after 1 year, in the absence of reduced left ventricular ejection fraction (LVEF; <50%) or other primary indications for therapy.¹ Although the benefits of beta-blockers following MI have been well established, there has been recent interest in the need to determine the optimal duration of therapy.

The ABYSS (Assessment of Beta-Blocker Interruption 1 Year After an Uncomplicated Myocardial Infarction on Safety and Symptomatic Cardiac Events Requiring Hospitalization) trial was a French multicenter, open-label, randomized, noninferiority trial to assess the hypothesis that interruption of beta-blocker therapy after 1 year post MI would be clinically safe and improve quality of life (QOL).² A total of 3,698 patients receiving beta-blocker therapy with an MI ≥6 months before enrollment were randomized 1:1 to either beta-blocker interruption (n = 1,846) or continuation (n = 1,852). Patients were excluded who had chronic heart failure (HF) or LVEF <40%, any cardiac event within 6 months of enrollment, or other primary indications for beta-blockers. The primary outcome was a composite of death, nonfatal MI, nonfatal stroke, or hospitalization for cardiovascular (CV) reasons. The main secondary outcome was QOL, as assessed by the EuroQol 5 Dimension™ (EQ-5D [EuroQol Research Foundation, Rotterdam, The Netherlands]) questionnaire.

The median time to randomization following MI was 2.9 years (interquartile range [IQR], 1.2-6.4 years). Most patients had an index ST-segment elevation MI (63%) and nearly all had undergone revascularization (95%; 91.7% with complete revascularization). At a median follow-up of 3 years (IQR, 2-4 years) and a noninferiority margin of <3 percentage points in an intention-to-treat analysis, the primary outcome occurred in 23.8% of patients in the interruption group and 21.1% of patients in the continuation group (risk difference 2.8 percentage points (95% confidence interval [CI], <0.1-5.5 percentage points), which did not reach the prespecified threshold for noninferiority (hazard ratio, 1.16; 95% CI, 1.01-1.33; p = 0.44 for noninferiority).² The notable difference in secondary endpoints was in hospitalization for CV reasons, specifically coronary-related events (18.9% interruption vs. 16.6% continuation) and HF-related events (1.8% interruption vs. 1.2% continuation). The change in EQ-5D score from baseline to last follow-up was 0.033 ± 0.15 in the interruption group and 0.032 ± 0.164 in the continuation group (mean difference 0.002; 95% CI, -0.008 to 0.012).² The beta-blockers commonly prescribed in the study lack robust data showing benefit after MI. For instance, the most common beta-blocker prescribed at enrollment was bisoprolol (71.5%), whereas only 1-1.3% of patients were taking metoprolol or carvedilol. The trial design was also limited by lack of blinding and doses of beta-blockers lower than those used in randomized controlled trials establishing efficacy after MI.

In summary, interruption of long-term beta-blockers in the ABYSS trial did not meet the threshold of noninferiority regarding the composite outcome of death, nonfatal MI, nonfatal stroke, or hospitalization for CV reasons. These findings do not support interruption of a chronic beta-blocker treatment in patients post MI. These findings may be driven by antianginal properties of beta-blockers, and interruption may increase the risk of recurrent angina and the need for rehospitalization. In addition, and perhaps contrary to popular opinion, there was no significant improvement in QOL noted with beta-blocker interruption. An individualized approach is required regarding beta-blocker therapy and further studies, such as the REDUCE-AMI (Randomized Evaluation of Decreased Usage of Beta-Blockers After Acute Myocardial Infarction) trial,³ are needed to determine the optimal duration of use in patients without alternative indications after acute MI with preserved left ventricular function.

References

1. Virani SS, Newby LK, Arnold SV, et al.; Writing Committee Members. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2023;82:833-955.
2. Silvain J, Cayla G, Ferrari E, et al.; ABYSS Investigators of the ACTION Study Group. Beta-blocker interruption or continuation after myocardial infarction. N Engl J Med 2024;391:1277-86.
3. Yndigegn T, Lindahl B, Mars K, et al.; REDUCE-AMI Investigators. Beta-blockers after myocardial infarction and preserved ejection fraction. N Engl J Med 2024;390:1372-81.