Stopping beta-blockers after a year of regular use does not appear to increase the risk of adverse clinical outcomes in myocardial infarction (MI) survivors without evidence of left ventricular systolic dysfunction or heart failure (HF), as shown in the SMART-DECISION trial.
Over a median follow-up of 3.1 years, the primary endpoint of a composite of death from any cause, recurrent MI, or hospitalization for HF occurred in 7.2 percent of patients who were taken off beta-blocker therapy vs 9 percent of those who stayed on it. [N Engl J Med 2026;394:1302-1312]
The trial met the prespecified noninferiority margin of 1.4 (hazard ratio [HR], 0.80, 95 percent confidence interval [CI], 0.57–1.13), establishing the noninferiority of a beta-blocker discontinuation strategy (p=0.001), according to senior investigator Prof Joo-Yong Hahn from Samsung Medical Center, Seoul, South Korea, who reported the results at the annual ACC meeting.
“In the context of contemporary secondary prevention, the results of the SMART-DECISION trial show that discontinuation of beta-blocker therapy beyond the first year after MI may be a reasonable strategy in selected patients who are in stable condition without HF or left ventricular systolic dysfunction and that routine long-term continuation may not be required in this population,” Hahn said.
“In practice … discontinuation can be considered through shared decision-making and with monitoring of blood pressure and heart rate. For patients with beta-blocker-related side effects—fatigue, dizziness, bradycardia, hypotension—the case for discontinuation is even stronger,” he added.
Diverging results
The present data differ from those presented in the ABYSS trial, which compared continuation of long-term beta-blocker therapy with interruption of therapy in patients with a history of MI. ABYSS showed that its primary endpoint of a composite of death, nonfatal MI, nonfatal stroke, or hospitalization for cardiovascular reasons at the longest follow-up (median 3 years) occurred more frequently in the interruption group than in the continuation group (23.8 percent vs 21.1 percent; HR, 1.16, 95 percent CI, 1.01–1.33; p=0.44 for noninferiority). [N Engl J Med 2024;391:1277-1286]
“The apparent discrepancy in results between the ABYSS and SMART-DECISION trials may be explained by key differences in trial design and clinical context,” Hahn said.
Notably, the two trials had different primary endpoints, and the one used in ABYSS might be less suitable for an open-label trial and more susceptible to clinical decision making than hard clinical endpoints, such as death and MI, Hahn pointed out.
Additionally, “background secondary prevention appeared to be more intensive in the SMART-DECISION trial, with more frequent use of ezetimibe and greater use of P2Y12 inhibitor monotherapy rather than aspirin, and lower low-density lipoprotein cholesterol levels were achieved,” he continued.
Finally, SMART-DECISION involved a population in highly stabilized condition, with at least 1 year of beta-blocker therapy before enrolment and undergoing randomization a median of 4.7 years after the index MI event, Hahn noted. ABYSS, on the other hand, included patients who were on a minimum of 6 months of beta-blocker therapy, with randomization occurring a median of 2.9 years after the index MI event.
Broad applicability
SMART-DECISION is “a very important study that will have broad applicability… This is something that I'll be able to put into practice when I get back to the office,” commented Dr Nicole Bhave from the University of Michigan Medical School, Ann Arbor, Michigan, US, during a press briefing.
Bhave underscored the pill burden in post-MI care and whether clinicians could actively reduce it, noting that patients could be overwhelmed by the number of medications that they had to take. “I think SMART-DECISION demonstrated in a more definitive fashion than ABYSS that, yes, at 1 year, it is safe in patients with normal ejection fraction and no atrial fibrillation to stop that beta-blocker.
“The other important thing to consider is that if the patient has another indication for a beta-blocker, [physicians have] to explain why they need to stay on it,” she said.
SMART-DECISION
SMART-DECISION included 2,540 stable post-MI patients (mean age 63.2 years, 12.8 percent female, 56.8 percent had ST-segment elevation MI), with the vast majority (98 percent) having undergone coronary revascularization at the time of the index MI event.
The patients were randomly assigned to either discontinue (n=1,246) or continue (n=1,249) their beta-blocker therapy. The beta-blockers used in the cohort were carvedilol (47.6 percent), bisoprolol (32.3 percent), and nebivolol (19.9 percent).
Results for the secondary endpoints showed no significant differences between the discontinuation and continuation groups. These included death from any cause (2.4 percent vs 3.4 percent), recurrent MI (2.3 percent vs 2.6 percent), hospitalization for HF (2.2 percent vs 2.1 percent), death from cardiovascular cause (1.6 percent vs 1.9 percent), stroke (0.7 percent vs 1.8 percent), and atrial fibrillation (1.5 percent vs 1.8 percent), among others.
In an exploratory analysis, a composite of death, nonfatal MI, nonfatal stroke, or hospitalization for cardiovascular reasons—the primary endpoint in ABYSS—occurred in 11 percent of patients in the discontinuation group vs 14.5 percent of those in the continuation group.
Serious adverse events were similar between the two groups, occurring in 11.5 percent of patients in the discontinuation group and 13.4 percent in the continuation group. Serious cardiac events were reported in 5.7 percent and 6.1 percent of patients in the respective groups.