Heart Health
Lauren Howell, PharmD
The long-term use of ß-blockers in patients with acute myocardial infarction (MI) who undergo early coronary angiography and have a preserved left ventricular ejection fraction may not lower the risk of death or a new MI as previously believed, revealed a study published in the April 18, 2024, issue of NEJM. The results of this study are in direct opposition to what most practitioners have been taught.
Since most trials that have shown a benefit of ß-blocker treatment after MI were conducted in the 1980’s, authors of this study wanted to investigate whether this benefit still exists with modern technology and treatments, including troponin-based diagnosis of MI, treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists.
Study design
In this registry-based, prospective, parallel-group, open-label, randomized clinical trial performed at 45 centers in Sweden, Estonia, and New Zealand, patients with an acute MI who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% were randomized to either receive long-term treatment with a ß-blocker or no ß-blocker treatment.
To be included, patients had to provide written informed consent 1 to 7 days after MI, and undergo coronary angiography and echocardiography with a preserved left ventricular ejection fraction of greater than or equal to 50%. They were also required to have obstructive coronary artery disease as documented by coronary angiography at any point before randomization. Patients who had an indication for or contraindication for ß-blocker treatment were excluded from the study.
Patients who were randomly assigned to receive ß-blocker treatment were prescribed metoprolol or bisoprolol during the remaining hospital stay and for continued use after discharge. Prescribers were encouraged to aim for a daily dose of at least 100 mg for metoprolol or 5 mg for bisoprolol.
Results
The primary endpoint was a composite of death from any cause or new MI. Safety endpoints included hospitalization for bradycardia, second or third degree atrioventricular block, hypotension, syncope, implantation of a pace maker, asthma, COPD and stroke.
The median age of patients included in the study was 65 years, 22.5% were women, and 35.2% had an ST-segment elevation MI. At discharge, 97.4% of patients were receiving aspirin, 95.8% a P2Y12 receptor blocker, 80.2% an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and 98.5% a statin.
Of the patients who were randomized to the ß-blocker group, 62.2% were treated with metoprolol and 37.8% were treated with bisoprolol. The median starting dose of metoprolol was 50 mg and the median starting dose of bisoprolol was 2.5 mg. The median target dose of metoprolol was 100 mg and the median target dose of bisoprolol was 5 mg.
Of the individuals assigned to the ß-blocker group, 90.6% were still taking ß-blockers after 6 to 10 weeks, and 81.9% were after 11 to 13 months. In the no ß-blocker group of study participants, 11.3% were taking ß-blockers after 6 to 10 weeks, and 14.3% were after 11 to 13 months.
During a mean follow-up period of 3.5 years, death from any cause or a new MI occurred in 7.9% of patients in the ß-blocker group and 8.3% in the no ß-blocker group. This was not found to be statistically significant. The incidence of safety endpoints also was similar between the two groups.
What does this mean?
More research should be done to evaluate the efficacy of ß-blockers in patients with an acute MI who undergo coronary angiography and have a mid-range ejection fraction of 40% to 49%, since these patients were excluded from this trial.
Additionally, the cross-over between groups should be considered as a possible reason no difference in the primary endpoint was seen between groups. Researchers should also determine the efficacy of nonselective ß-blockers in the same population that was investigated in this study. ■