A new study may have failed to demonstrate the cardiovascular safety of interrupting long-term beta-blocker therapy compared with continuation of the treatment in patients with a history of myocardial infarction who didn't need beta-blockers for other reasons.

In the open-label, noninferiority, randomized ABYSS trial, presented at the European Society of Cardiology (ESC) Congress 2024, researchers from the ACTION Group recruited 3,698 patients from 49 sites in France. The patients were randomly assigned 1:1 to receive either interrupting or continuing beta-blocker medication.

The trial was initiated as a result of improvements in myocardial infarction (MI) management and observational data questioning the necessity of beta-blockers beyond 1 year post-MI, given potential side effects of unnecessary treatment.

Patient characteristics:

• Median time between last MI and randomization: 2.9 years (interquartile range = 1.2–6.4 years)
• Mean age: 64 years
• 17% female participants
• Median follow-up: 3 years.

Inclusion criteria:

• Prior MI
• Long-term beta-blocker therapy
• Left ventricular ejection fraction of at least 40%
• No cardiovascular events in the previous 6 months.

Among the key findings were:

• Primary Outcome: A composite of death, nonfatal MI, nonfatal stroke, or hospitalization for cardiovascular reasons occurred in 23.8% of patients in the interruption group vs 21.1% of those in the continuation group (risk difference = 2.8 percentage points, 95% confidence interval [CI] < 0.1–5.5; hazard ratio [HR] = 1.16, 95% CI = 1.01–1.33, P = .44 for noninferiority).
• Noninferiority Analysis: The trial did not meet the predefined noninferiority criterion, as the upper boundary of the 95% CI (5.5 percentage points) exceeded the predefined noninferiority margin of 3 percentage points.
• Mortality: Death occurred in 4.1% of patients in the interruption group vs 4.0% in the continuation group.
• Recurrent MI: 2.5% in the interruption group vs 2.4% in the continuation group experienced a recurrent MI.
• Hospitalization: 18.9% in the interruption group vs 16.6% in the continuation group were hospitalized for cardiovascular causes.
• Physiological Effects: Beta-blocker interruption was associated with significant increases in systolic and diastolic blood pressure and heart rate at 6 months (all P < .001 vs beta-blocker continuation) and during study follow-up.
• Quality of Life: Beta-blocker interruption did not improve patients' quality of life as measured by the European Quality of Life–5 Dimensions questionnaire.

"We conducted the ABYSS trial to provide conclusive randomized 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," underscored principal investigator Johanna Silvain, Professor of the Sorbonne University in Paris.

The results of the ABYSS trial need to be considered alongside other recent findings such as those from the open-label REDUCE-MI trial and ongoing studies to provide additional evidence on optimal beta-blocker use after MI.

The principal investigator declared the following during the last 2 years:  consulting fees or lecture fees from BIOTRONIK FRANCE SAS; SANOFI AVENTIS FRANCE, CSL BEHRING S.A.; travel support/hospitality from ABBOTT MEDICAL FRANCE SAS, BIOTRONIK FRANCE SAS, MEDTRONIC INTERNATIONAL TRADING SARL, NOVO NORDISK; stockholder with 4P-PHARMA.