By Michael H. Crawford, MD, Editor
Synopsis: An analysis of the secondary outcomes in the French multicentered study of beta-blocker withdrawal in patients with uncomplicated myocardial infarction after one year led to increases in heart rate and blood pressure with potentially deleterious outcomes, especially in patients with a history of hypertension.
Source: Procopi N, Zeitouni M, Kerneis M, et al. Beta-blocker interruption effects on blood pressure and heart rate after myocardial infarction: The AβYSS trial. Eur Heart J. 2025;46(29):2894-2902. [Erratum in: Eur Heart J. 2025; Jul 10. doi: 10.1093/eurheartj/ehaf510. {Online ahead of print}.]
The French multicenter, open-label, randomized trial (AβYSS) of discontinuing beta-blockers at one year post-myocardial infarction (MI) in patients with preserved left ventricular (LV) systolic function showed that the primary endpoint of death, MI, stroke, and hospitalization for cardiovascular reasons was more frequently observed in the interruption group than the continuation group (24% vs. 21%; P = 0.047). This report provides the secondary results of the AβYSS trial, which included heart rate (HR), blood pressure (BP), double product (DP; HR × systolic BP), and an analysis of the primary and secondary outcomes stratified by the presence or absence of a prior history of hypertension.
At 49 centers, 3,698 patients (83% men, mean age 64 years) were randomized. Among these patients, 43% had a history of hypertension and were older than the patients without a history of hypertension (age 67 vs. 61 years). They had more cardiovascular disease (CVD) risk factors, were on higher doses of beta-blockers, and were more likely to be taking angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs), calcium channel blockers, or diuretics. At six months of follow-up, those in the beta-blocker withdrawal group had significantly higher systolic BP (+3.7 mmHg), diastolic BP (+3.3 mmHg), and DP (+1,616) (all P < 0.001) compared to those who continued beta-blocker therapy. These changes persisted for the median follow-up of three years despite the escalation of other antihypertensive agents or increases in the beta-blocker dose.
Patients with a prior history of hypertension had a higher risk of CVD events compared to those without this history (26% vs. 19%; hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.01-1.36; P = 0.03), which was driven mainly by hospitalization for CVD events such as acute coronary syndrome, heart failure, and supraventricular tachycardia (23% vs. 19%; HR, 1.25; 95% CI, 1.0-1.57; P = 0.05). The authors concluded that withdrawing beta-blockers in patients after an uncomplicated MI leads to significant increases in BP and HR, which may explain the potentially deleterious outcomes observed in AβYSS, especially in patients with a history of hypertension.
Commentary
In the June 2024 issue of Clinical Cardiology Alert, we discussed the REDUCE AMI study, a large, multicenter, international, randomized clinical trial of long-term beta-blocker therapy compared to no such therapy after acute MI in patients who had coronary angiography-guided therapy and normal left ventricular ejection fraction.1 It found that mortality and recurrent MI was not different between the two groups after a 3.5-year follow-up period. Although REDUCE-AMI and AβYSS are different in several important ways, they address the same issue. In AβYSS, everyone received beta-blockers initially, then half of the subjects had them discontinued. AβYSS showed that withdrawing beta-blockers, especially in those with a history of hypertension, led to a small but significant increase in adverse outcomes, which was mainly the result of an increase in hospitalization for CVD events. The REDUCE-AMI primary outcome did not include hospitalization for CVD events or stroke, and the researchers did not monitor HR and BP. Both studies enrolled relatively low-risk post-MI patients with no indications for beta-blocker therapy.
Another difference between these two trials is the beta-blocker used. In AβYSS, 72% of the patients were taking bisoprolol, whereas in REDUCE-AMI, only 38% of the patients were taking bisoprolol and the majority were taking metoprolol (62%). Both beta-blockers are β1-receptor selective, so their effects should be similar, but it raises the question of whether all beta-blockers produce the same effects. Also, the hypertensive patients in AβYSS were taking higher doses of beta-blockers and more drugs that lower BP. Thus, drug management in hypertensive patients is more complicated, and extremes of BP in either direction should be avoided when manipulating therapy.
How do we reconcile these two studies? In an editorial accompanying the AβYSS report, John Cleland from the British Heart Foundation CV Research Center recommends that low-risk patients without indications for beta-blockers receive them initially and then the need for them be reviewed after six to 12 weeks.2 If there is no evidence of LV systolic dysfunction, hypertension, arrhythmias, or angina, they can be withdrawn. He gives similar advice for ACEI/ARB and dual antiplatelet therapy. This seems like a reasonable compromise until more data are available.
Michael H. Crawford, MD, is Professor Emeritus of Medicine and Consulting Cardiologist, UCSF Health, San Francisco.
References
1. Yndigegn T, Lindahl B, Mars K, et al. Beta-blockers after myocardial infarction and preserved ejection fraction. N Engl J Med. 2024;390(15):1372-1381.
2. Cleland JGF. Staring into the AβYSS: How many pills and for how long after myocardial infarction? Eur Heart J. 2025;46(29):2903-2905.
