ABYSS trial does not demonstrate safety of beta-blocker interruption after heart attack
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Key takeaways:
- Optimal duration of beta-blockers after a heart attack remains unknown.
- The ABYSS trial provides new insights on continued vs. interrupted beta-blocker treatment.
In the ABYSS trial, a strategy of interrupting long-term beta-blocker treatment was not noninferior to continued use for the primary composite outcome of death, myocardial infarction, stroke or hospitalization for CV reasons.
“In addition, beta-blocker interruption did not result in an improvement in patient quality of life, and resulted in increased blood pressure, resting heart rate and a higher rate of hospitalization for CV reasons,” Johanne Silvain, MD, PhD, professor of cardiology at Sorbonne University and director of the ICU at the Institut de Cardiologie of the Hospital Pitié-Salpêtrière in Paris, said during a press conference at the European Society of Cardiology Congress.
The ABYSS trial, which was simultaneously published in The New England Journal of Medicine, included nearly 3,700 patients in France with a history of uncomplicated MI and without reduced left ventricular ejection fraction ( 40%) who were randomly assigned to continue or interrupt their long-term beta-blocker therapy. During a median follow-up period of 3 years, a primary endpoint event — which included death, nonfatal MI, nonfatal stroke or hospitalization for CV reasons — occurred in 23.8% of the group assigned to beta-blocker interruption compared with 21.1% of the group assigned to beta-blocker continuation (HR = 1.16; 95% CI, 1.01-1.33; P = .44 for noninferiority).
Beta-blocker interruption vs. continuation
ABYSS was an open-label, randomized, noninferiority trial that was conducted at 49 sites in France. Upon enrollment, all patients were on a beta-blocker. The most frequently used beta-blocker was bisoprolol (in 71.5% of patients). Other beta-blockers being used at baseline included acebutolol in 10.8%, atenolol in 8.7%, nebivolol in 5.9%, metoprolol in 1.2% and carvedilol in 1.1%. Other beta-blockers were used in less than 1% of patients. Patients were randomly assigned with guidance to use the same agent at the same dose.
Those enrolled had a mean age of 64 years and 83% were men. Median time from last MI to randomization in ABYSS was 3 years. About two-thirds of patients had a previous STEMI; nearly 8% had a history of more than one MI. Ninety-five percent of patients had undergone coronary revascularization for the index MI.
All patients were followed for a median of 3 years. Longest follow-up was out to 5 years, according to Silvain.
There was a 16% relative risk increase in the primary composite outcome among the beta-blocker interruption group, Silvain said. “If you look at the components [of the primary composite outcome], there was not much difference in death, MI and stroke, but an increase in new hospitalizations for CV events,” he said.
Hospitalization for CV reasons occurred in 18.9% of the interruption group compared with 16.6% of the continuation group.
With regard to secondary outcomes, the researchers found no difference in a composite endpoint of death, MI, stroke and hospitalization for HF (8.4% for beta-blocker interruption vs. 7.6% for continuation; HR = 1.11; 95% CI, 0.88-1.39), but Silvain said the curves diverged over time and perhaps longer follow-up would show a difference.
When the researchers looked at patient-reported quality of life, as measured by the European Quality of Life-5 Dimensions (EQ-5D) questionnaire, interrupting beta-blocker treatment did not result in improved quality of life at 6 or 12 months compared with baseline.
BP and heart rate were measured at each follow-up. At 6 months after randomization, Silvain said the researchers found significant increases in the beta-blocker interruption group in systolic BP (+ 3.7 mm Hg), diastolic BP (+ 3.9 mm Hg), resting heart rate (+ 9.8 bpm), and the double product (+ 1,616), which consists of systolic BP multiplied by the heart rate, compared with continued treatment (P < .001 for all).
Looking at a subgroup of patients with baseline hypertension, which comprised 43% of patients enrolled in ABYSS, there was an even greater increase in the primary composite endpoint (adjusted HR = 1.18; 95% CI, 1.01-1.36; P = .03), according to Silvain.
Results in context
“ABYSS did not demonstrate the safety of beta-blocker interruption in MI patients with preserved left ventricular ejection fraction, a strategy that led to a higher rate of hospitalizations, especially in hypertensive patients,” Silvain said during the press conference.
The researchers cited several limitations of the trial, including its open-label design and conduct solely in France.
In an editorial published in NEJM, Tomas Jernberg, MD, PhD, from the department of clinical sciences at Danderyd Hospital, Karolinska Institute, in Stockholm, said the primary reason behind starting or continuing beta-blocker treatment cannot solely be attributed to beta-blockers’ “acceptable side effect profile.”
Both the researchers and Jernberg said the results of the ABYSS trial should be considered within the context of recent the REDUCE-AMI trial, which found that long-term beta-blocker use did not reduce risk for death or new MI compared with no use in patients with acute MI and preserved ejection fraction.
“Among patients with myocardial infarction and a preserved left ventricular ejection fraction, the findings of the REDUCE-AMI trial placed the use of beta-blockers for secondary prevention squarely on the ‘injured-reserve’ list in April 2024,” Jernberg wrote in the editorial. “The results of current trials will provide additional data on whether the use of these drugs in this population may be approaching final retirement.”
References:
- Jernberg T, et al. N Engl J Med. 2024;doi:10.1056/NEJMe2409646.
- Silvain J, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2404204.
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Silvain J. Hot line 1. Presented at: European Society of Cardiology Congress; Aug. 30-Sept. 2, 2024; London (hybrid meeting).
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