ABYSS Trial: No Difference in Outcomes Continuing or Stopping Beta-Blockers Following MI

For patients with a history of myocardial infarction, continuing treatment with beta-blockers could be an unnecessary practice, according to the results of the ABYSS trial.

Coming less than a year after REDUCE-AMI thrust the issue into the spotlight, the ABYSS trial, which was presented at the European Society of Cardiology (ESC) Congress 2024, provides the community with further evidence surrounding use of beta-blocker use in patients with recent myocardial infarction and preserved ejection fraction, but investigators caution further research is needed to solidify these findings.

“We conducted the ABYSS trial to provide conclusive randomised data on the effects of beta-blocker interruption vs. continuation on cardiovascular events and quality of life, but we were unable to show safety preservation in terms of clinical events nor any benefit on quality of life with beta-blocker interruption,” said principal investigator Johanne Silvain, MD, PhD, head of Department of Cardiology at the Pitié-Salpêtrière University Hospital andof the Sorbonne University, Paris, France.

At the American College of Cardiology 2024 Scientific Sessions, the REDUCE-AMI trial brought forth significant data challenging the benefit of beta-blocker use in patients with provide significant benefit for patients with a recent myocardial infarction and normal left ventricular ejection fraction (LVEF). A registry-based, prospective, open-label, parallel-group, randomized clinical trial, results of the study suggested beta-blocker use provided no significant reduction in risk of all-cause mortality or new myocardial infarction among patients with an LVEF of 50% or greater.

Simultaneously published in the New England Journal of Medicine, ABYSS was an open-label, non-inferiority, randomized conducted by Silvain and colleagues from the ACTION Group. The trial enrolled 3,698 patients from 49 sites in France and randomized them in a 1:1 ratio to interrupting or continuing their beta-blocker medication.

For inclusion in the trial, patients were required to have a history of prior myocardial infarction taking long-term beta-blockers, with a left ventricular ejection fraction of at least 40%, and no cardiovascular events in the previous 6 months. The overall study cohort had a mean age of 63.5 (SD, 11) years, 17.2% were women, the median time between myocardial infarction and randomization was 2.9 (interquartile range [IQR], 1.2 to 6.4) years, and the median follow-up was 3.0 years. (IQR, 2.0 to 4.0)

The trial leveraged a composite primary endpoint consisting of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons at the longest follow-up. For the purpose of analysis, the investigators’ noninferiority analyses defined noninferiority as a between-group absolute difference of <3 percentage points. The trial’s secondary outcome of interest was change in quality of life as measured by the European Quality of Life–5 Dimensions (EQ-5D) questionnaire.

Upon analysis, results indicated a primary outcome event occurred among 23.8% of the interruption group compared to 21.1% of the continuation group (risk difference, 2.8 percentage points; 95% CI, <0.1 to 5.5; HR, 1.16; 95% CI, 1.01 to 1.33; P = .44 for noninferiority). Secondary outcomes analysis revealed the mean change in EQ-5D from baseline to last follow-up was0.033±0.150 in the interruption group and 0.032±0.164 in the continuation group (mean difference, 0.002; 95% CI, −0.008 to 0.012).

When assessing individual components of the primary outcome, investigators found similar rates of death (4.1% vs 4.0%), myocardial infarction (2.5% vs 2.4%), stroke (1.0% vs 1.0%) among those in the interruption and continuation groups, respectively. However, investigators pointed out hospitalization for cardiovascular causes occurred among 18.9% of the interruption group and 16.6% of the continuation group.

“Differences between the groups with respect to hospitalisation for cardiovascular reasons and the negative effect on blood pressure levels, together with the absence of quality-of-life improvement do not support interruption of a chronic beta-blocker treatment in post-MI patients,” Silvain added. “These results must be put into context with recent findings from the open-label REDUCE-MI trial and ongoing trials to provide additional evidence on the optimal use of beta-blockers after [myocardial infarction].”

Tomas Jernberg, MD, PhD, professor of Cardiology and head of the Department of Clinical Sciences at Danderyd Hospital of the Karolinska Institute, published an editorial alongside the ABYSS trial in the New England Journal of Medicine commending the investigators of ABYSS and REDUCE-AMI for well-run trials, but cautioned against overinterpretation of results in light of other ongoing trials he expects to bring additional clarity to the topic.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with myocardial infarction and a preserved left ventricular ejection fraction before definitively updating guidelines, because the investigators in these trials will soon be reporting their findings,” Jernberg wrote. “Taken together, the results of the ABYSS, REDUCE-AMI, and ongoing trials will most likely provide firm evidence regarding beta-blocker treatment in this patient population.”