Setbacks after stopping beta-blockers

LONDON — It may not be recommended for patients with pre-existing conditions. Myocardial infarction The researchers caution that discontinuing long-term beta-blocker therapy may preserve left ventricular function.

In the randomized ABYSS trial, stroke When comparing patients who stopped taking beta-blockers with those who continued to take them, patients who stopped taking them had a higher rate of hospitalization for cardiovascular disease.

Discontinuation was also associated with increases in blood pressure and heart rate but no improvement in quality of life.

“We thought that beta-blockers could be safely discontinued and that this would improve quality of life, but the trial results show that this is not the case,” said lead researcher Joanne Sylvain, MD, PhD, of Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings at the European Society of Cardiology (ESC) congress.

The results of the simultaneous Publish online of New England Journal of Medicinecast doubt on current guidelines that suggest that beta-blockers can be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after myocardial infarction, but trials demonstrating the efficacy of these agents were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which dramatically reduced the risk of myocardial infarction. heart failure Sylvain also explained death following a myocardial infarction.

This raises questions about the added benefit of lifelong beta-blocker therapy for patients who have suffered a myocardial infarction, have preserved left ventricular ejection fraction, and have no other major indications for beta-blocker therapy.

ABYSS TRIAL

To address this issue, the open-label, noninferiority ABYSS trial randomly assigned 3698 patients with a history of myocardial infarction to discontinue or continue beta-blocker therapy. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker therapy, and had not experienced a cardiovascular event in the previous 6 months.

With a median follow-up of 3 years, the primary outcome composite of death, myocardial infarction, stroke, or cardiovascular hospitalization occurred more frequently in the discontinued group than in the continued group (23.8% vs 21.1%; hazard ratio 1.16; 95% CI, 1.01 to 1.33), which did not meet the criteria for noninferiority of discontinuation compared with continued beta-blocker therapy (P noninferiority = .44).

The difference in event rates between the two groups was due to cardiovascular hospitalizations, which occurred more frequently in the discontinuation group than in the continuation group (18.9% vs. 16.6%).

Other key findings showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, blood pressure and heart rate increased in the discontinuation group: systolic blood pressure increased by 3.7 mm Hg, diastolic blood pressure increased by 3.9 mm Hg, and resting heart rate increased by 9.8 beats per minute.

“We were unable to demonstrate non-inferiority of discontinuing beta-blockers with regard to cardiovascular events. [but we] “This strategy increased blood pressure and heart rate and did not improve quality of life, but it did show signs of safety,” Sylvain said.

“Recent guidelines suggest that it may be reasonable to discontinue beta-blockers in this patient population, but given our results, we have no intention of stopping these medications if they are well tolerated,” he said.

Sylvain said he was surprised that the group who stopped taking beta-blockers did not see an improvement in quality of life: “We've always been told that beta-blockers have a lot of side effects, so we expected that patients who stopped taking the drug would have an improvement in quality of life.”

One possible reason for the lack of improvement in quality of life is that study participants had been taking beta-blockers for several years, “so we may have selected patients who tolerated these drugs quite well. Those who had tolerance problems had probably already stopped taking them,” he explained.

Moreover, the patient population had relatively high quality-of-life scores at baseline, “and because they were well treated and the therapies they were receiving were well tolerated, it may be difficult to further improve their quality of life,” he said.

REDUCE-AMI Study

At first glance, the ABYSS results are Reduce AMI This study failed to demonstrate superiority of beta-blocker therapy compared with no beta-blocker therapy in patients with acute myocardial infarction with preserved left ventricular ejection fraction.

However, Sylvain noted that the primary endpoint of REDUCE-AMI was a composite of death from any cause or new myocardial infarction, which did not include hospitalization for cardiovascular disease, which was the main factor behind the difference in results in the ABYSS study.

“We found that stopping beta-blockers was associated with an increase in hospitalizations for coronary artery disease, and we must remember that beta-blockers were developed to ameliorate coronary artery disease,” he said.

“A bit inconclusive”

ABYSS discussant for the ESC HOTLINE session, Jane Armitage, MBBS, University of Oxford, UK, noted some limitations of the study and reported that the results were “somewhat inconclusive.”

The open-label design may have introduced some bias with respect to the cardiovascular hospitalization endpoint, she said.

“The decision to admit a patient is [the] “Hospital trials can be somewhat subjective and dependent on the doctor's knowledge of the treatment allocation, so ideally I would like to have a blinded trial. I think there is some doubt there,” she explained.

She also questioned whether the non-inferiority margin could have been expanded given the higher-than-expected event rate.

Armitage said further data on this issue will come from several ongoing trials.

“The combined results of the ABYSS and REDUCE-AMI trials suggest that patients with ventricular septal defect may stop beta-blocker therapy without serious cardiac events if their left ventricular ejection fraction is preserved,” said Thomas Jernberg, M.D., Ph.D., of the Karolinska Institutet in Stockholm, Sweden. Accompanying editorial.

However, “due to the anti-ischemic effects of beta-blockers, discontinuation may increase the risk of recurrence.” Angina pectoris And then there is the need for readmissions,” he added.

“It would be prudent to await the results of additional trials of beta-blockers in patients with myocardial infarction and preserved ejection fraction before making a final update to the guidelines,” Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION research group. Sylvain, Armitage and Jernberg report no relevant financial relationships.