LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.
In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.
Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.
The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.
Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained.
This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
The ABYSS Trial
To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months.
At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).
The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).
Other key results showed that there was no difference in quality of life between the two groups.
However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.
“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.
“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.
Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”
One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.
In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.