Alyssa Rubey, PharmD, New Ulm Medical Center
Background: Beta-blockers are a part of guideline recommended therapy for most patients with chronic coronary disease (CCD) for secondary prevention of major adverse cardiovascular events (MACE). Guidelines recommend reassessing the need for beta-blocker therapy after one year for patients with no history of left ventricular ejection fraction (LVEF) ≤50%, angina, arrhythmias, or uncontrolled hypertension. With improvements in reperfusion therapy after myocardial infarction (MI), the need for ongoing beta-blocker therapy has been questioned.
Objective: The Assessment of Beta-Blocker Interruption 1 Year after an Uncomplicated Myocardial Infarction on Safety and Symptomatic Cardiac Events Requiring Hospitalization (ABYSS) study was conducted to determine non-inferiority of interruption of beta-blocker therapy compared to continuation of beta-blocker therapy as guideline recommended for secondary prevention of MACE.
Study Design: The ABYSS trial was a multicenter, noninferiority study utilizing prospective, randomized, open-label, blinded end-point design. Patients were randomized between August 18, 2018 through September 12, 2022 to two treatment groups: interruption of therapy, where patients were tapered off beta-blocker therapy, or continuation of beta-blocker therapy, where no changes were made. Patients were included if they were on long-term beta-blocker therapy regardless of dose or agent and have a history of MI a minimum of six months prior to enrollment. Patients were excluded if they had chronic heart failure, a LVEF ≤ 40%, or another primary indication for beta-blocker therapy. The primary outcome was a composite of death, non-fatal MI, non-fatal stroke, and hospitalization for any other cardiovascular reason. Noninferiority in this trial was defined as a between group difference of less than 3% for the upper limit of the 95% confidence interval. The main secondary endpoint was the difference of quality of life measured by the European Quality of Life-5 Dimensions (EQ-5D) questionnaire, in which scores range from zero to one, with one indicating better health status.
Results: A total of 3698 patients were randomized with 1846 patients in the interruption group and 1852 patients in the continuation group. The mean age of the patients was 63.5 years with 17.2% of patients being women. The median time between MI and study randomization was 2.9 years. The median LVEF was 60% in both groups and 23.4% of patients had a LVEF of 40-50%. The majority of patients (71.5%) were taking bisoprolol. The risk difference between beta-blocker interruption and continuation was 2.8% (95% CI <0.1% to 5.5%), indicating that noninferiority was not met. Patients in the interruption group also had a non-statistically significant hazard ratio increase of 1.16 for the primary endpoint (95% CI 1.01 to 1.33, P=0.44). When looking at individual components of the primary composite outcome, hospitalization from any cardiovascular reason seems to be the driver of the risk difference, with 18.9% in the interruption group and 16.6% in the continuation group (risk difference 2.3%, 95% CI -0.1% to 4.8%). For the main secondary endpoint of change in quality of life, the mean difference in EQ-5D between the interruption group and the continuation group was 0.002 (95% CI -0.008 to 0.012) showing interruption of beta-blocker therapy had no significant effect on quality of life.
Conclusions: The ABYSS study was not able to prove beta-blocker discontinuation as noninferior to continued use of therapy, indicating that current recommendations of continued use for life should be upheld. Secondary endpoints indicated no difference in quality of life between interventions. The ABYSS trial was unique from similar trials in that it included patients with a comparatively lower LVEF of 40% and above, included hospitalization due to cardiovascular events in their composite primary outcome, and included a variety of beta-blockers with a majority taking bisoprolol (71%), acebutolol (10.8%), atenolol (8.7%), or nebivolol (5.9%). The remaining beta-blockers used by patients included metoprolol (1.2%), carvedilol (1.1%), celiprolol, sotalol, celectol, betaxolol, propranolol, and nadolol (all in <1.0%).
Key Points: Beta-blocker therapy after MI should be continued indefinitely unless otherwise contraindicated according to the ABYSS study. New studies continue to emerge surrounding the duration of use for beta-blockers in CCD with updates to current guidelines likely to be published in response to these new data.
Published March 7, 2025
Reference:
- Silvain J, Cayla G, Ferrari E, et al. Beta-Blocker Interruption or Continuation after Myocardial Infarction. N Engl J Med. 2024;391(14):1277-1286. doi:10.1056/NEJMoa2404204
- Virani SS, Newby LK, Arnold SV, et al. 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. Circulation. 2023;148(9):e9-e119. doi:10.1161/CIR.0000000000001168