Drop the Beta-Blocker Long After a Stabilized MI? Not a Bad Idea After All

NEW ORLEANS — The beta-blockers routinely used after myocardial infarction (MI) can be reasonably stopped after a year in some patients, the SMART-DECISION trial found.

In stabilized heart attack survivors without heart failure or left ventricular (LV) systolic dysfunction, stopping the beta-blockers led to major clinical outcomes on par with a continuation strategy in terms of combined all-cause death, recurrent MI, or heart failure (HF) hospitalization (7.2% vs 9.0%; HR 0.80, 95% CI 0.57-1.13), according to Joo-Yong Hahn, MD, of Samsung Medical Center in Seoul, Korea.

With the HR falling well below the trial’s prespecified noninferiority margin of 1.4, the beta-blocker discontinuation arm evidently met noninferiority (P=0.001), according to Hahn’s SMART-DECISION presentation here at the American College of Cardiology (ACC) annual conference.

“I cannot define at a single point when the beta-blocker would be safely discontinued,” Hahn told the audience. “But in my opinion, discontinuation of a beta-blocker beyond the first year of myocardial infarction would be a reasonable strategy in selected stable post-MI patients without left ventricular systolic dysfunction or heart failure.”

The study’s full manuscript was published simultaneously in the New England Journal of Medicine.

Being the first randomized study to demonstrate the noninferiority of beta-blocker discontinuation in these post-MI patients, SMART-DECISION thus offers a rebuke to the ABYSS trial.

In 2024, ABYSS had shown that heart attack survivors assigned to beta-blocker interruption fared worse clinically — namely with excess hospitalizations — compared with those who continued them. Notably, that trial had included a French population with a median left ventricular ejection fraction (LVEF) of 60%, similar to that in Korea’s SMART-DECISION.

Hahn reported that his group had an ABYSS-like exploratory endpoint (death from any cause, recurrent MI, stroke, or hospitalization for cardiovascular reasons) that still numerically favored beta-blocker discontinuation without reaching statistical significance (11.0% vs 14.5%; HR 0.89, 95% CI 0.68-1.16).

Beta-blockers have already been losing favorability in recent years, as mounting data suggest that long-term beta-blockers have little added benefit in contemporary practice to make up for potential side effects such as depression and fatigue. U.S. guidelines have already stopped recommending beta-blockers 1 year after an MI unless the patient has low LVEF, hypertension, arrhythmia, or another indication for them.

SMART-DECISION is “a very important study that will have broad applicability,” commented Nicole Bhave, MD, of University of Michigan Health in Ann Arbor. “This is something that I’ll be able to put into practice when I get back to the office.”

Bhave discussed the attractiveness of dropping beta-blockers from a pill burden perspective. “One of the things that I often think about when seeing a patient with the first myocardial infarction is the sheer number of pills that we’re putting them on. Dual antiplatelet therapy, statins … it’s overwhelming for them,” she said during a press conference.

“The other important thing to consider, because if the patient has another indication for the beta-blocker … it’s important for us to explain why they need to stay on, whether because of their Afib [atrial fibrillation] or their PVCs [premature ventricular contractions] or what have you,” Bhave nonetheless cautioned.

Beyond the scope of the trial is another important question: whether beta-blockers even merit upfront use in ST-segment elevation MI (STEMI) or lower-risk non-STEMI, as discussed during a separate town hall panel at ACC.

“I’ll go so far as to say that for a lower-risk ACS [acute coronary syndrome] patient in the hospital … if I am dealing with marginal blood pressure … I have a low threshold for not initiating [the beta-blocker]. For a patient that I consider to be otherwise low risk, who’s not having ventricular arrhythmias, whose ejection fraction is preserved, if I had an excuse, so to speak, for not starting it, I’m OK with that,” said Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, during that session.

The SMART-DECISION trial included 2,540 stabilized post-MI patients screened from 2021 to 2023. Participants were randomized 1:1 to discontinuation or continuation of beta-blockers that they’d already been on for over a year. Excluded were people with LVEF <40%, ongoing treatment for HF, or a history of Afib, among other criteria.

Average patient age was 63 years, with the cohort about 13% women. The index MI was a STEMI in about 57% of cases. Nearly 60% had multivessel disease. The revascularization strategy had been percutaneous coronary intervention in over 97% of patients.

At baseline, median LVEF was 59% and the median time from index MI to randomization was just under 5 years. The beta-blockers used at study entry were carvedilol (about 48%), bisoprolol (32%), and nebivolol (20%).

Secondary endpoints came out even between groups for the most part. These included all-cause death (2.4% vs 3.4%; HR 0.71, 95% CI 0.43-1.16), recurrent MI (2.3% vs 2.6%; HR 1.11, 95% CI 0.63-1.96), and hospitalization for HF (2.2% vs 2.1%; HR 0.82, 95% CI 0.42-1.57).

Only stroke reached a statistically significant advantage for beta-blocker discontinuation (0.7% vs 1.8%; HR 0.43, 95% CI 0.19-0.99).

The primary endpoint in the per-protocol population, accounting for crossovers, was similar (7.2% discontinuation vs 8.8% continuation; HR 0.79, 95% CI 0.56-1.12).

There was more uncontrolled tachycardia in the discontinuation group as early as the 12-month study visit (7.1% vs 1.5%), which persisted to the 30-month visit (6.5% vs 1.9%). Meanwhile, there was no excess in uncontrolled hypertension, according to the report.

SMART-DECISION’s open-label design was a major limitation of the trial. Results may also not generalize to higher-risk patients after MI or populations with greater comorbidity burden, Hahn cautioned, adding that the study also had low representation of women and people with mildly reduced LVEF.