By Michael H. Crawford, MD, Editor
SYNOPSIS: A large, contemporary, nationwide, observational study of post-myocardial infarction beta-blocker administration shows that after three months, there were no beneficial effects on adverse cardiovascular events to continued beta-blocker use.
SOURCE: Holt A, Blanche P, Zareini B, et al. Effect of long-term beta-blocker treatment following myocardial infarction among stable, optimally treated patients without heart failure in the reperfusion era: A Danish, nationwide cohort study. Eur Heart J 2021 Jan 11;ehaa1058. doi: 10.1093/eurheartj/ehaa1058. [Online ahead of print].
The long-term use of beta-blockers following myocardial infarction (MI) is based on older trials conducted before the widespread use of reperfusion, statins, and antiplatelet drugs beyond aspirin. Investigators from Denmark tested the hypothesis that beta-blocker use after three months post-MI in patients without heart failure was of no benefit.
Using the Danish National Patient Register, Holt et al identified patients age 30 to 85 years with a first MI admission who underwent a percutaneous coronary intervention (PCI) or coronary angiography between 2003 and 2018 and had never used beta-blockers. The study population included those patients who survived for 90 days and were prescribed statins and aspirin. The authors excluded patients with a contraindication for beta-blockers; another indication for beta-blockers; and those who had undergone a cardiac procedure or surgery beyond the initial PCI, before MI, or during the first 90 days after MI. Beta-blocker use was defined as beta-blockers started within the first 30 days post-MI. The primary outcomes were cardiovascular (CV) death, recurrent MI, and a composite of CV events. Secondary outcomes were potential beta-blocker adverse events. Those who received beta-blockers and those who did not were compared after adjustment for potential confounding.
Of the 30,177 patients included in the study, 58% underwent a primary PCI, 26% a subacute PCI, and 16% coronary angiography without intervention. At baseline, 82% were on beta-blockers (75% male; median age, 61 years) and 18% were not (68% male; median age, 62 years). Patients on beta-blockers were more likely to have undergone primary PCI, but other differences were not clinically significant. The proportion of patients on beta-blockers declined throughout the study period (92% in 2003-2005 to 67% in 2015-2018). Over the study period, 405 subjects died from CV causes, 1,859 experienced a recurrent MI, and 7,768 reached the composite endpoint. There was no difference in outcomes between those on beta-blockers compared to those not. Also, no association was found between beta-blockers and the risk of an adverse event requiring a hospital visit. As a negative control, the effect of beta-blockers on pneumonia was analyzed, and no association was found. Also, beta-blocker use did not affect all-cause mortality. The authors concluded there was no effect of beta-blocker treatment on long-term CV prognosis in optimally treated MI patients without heart failure who survived at least three months post-MI.
The most recent American College of Cardiology/American Heart Association guidelines recommend giving beta-blockers to MI patients after the first 24 hours, unless there are contraindications to their use, and continue those for at least three years.1 This recommendation is based on trials conducted in the era before reperfusion therapy, statin use, and advanced antiplatelet agents were available. Since reperfusion rapidly reduces sympathetic drive, beta-blocker therapy may not be as necessary as originally thought.
The Danish study was conducted in the reperfusion era. Patients with indications or contraindications for beta-blockers were excluded. Also, these authors optimized the use of other therapies of known value. Ninety-five percent of the Danish patients were taking aspirin and statins. In addition, Holt et al argued their work was a real-world experience, which complements randomized trial data. The guidelines recommend titrating metoprolol up to 200 mg/day, if possible, based on older, randomized trial data.1 The median metoprolol dose in the Holt et al study was 50 mg/day. Thus, one could argue subjects were underdosed. However, these high doses are used rarely, at least in my experience.
In the Holt et al study, there was no association between beta-blockers and adverse events that required going to the hospital. They did not study less significant nuisance adverse effects, but compliance with beta-blocker use was excellent. It is unknown why some patients were not treated with beta-blockers, but the data were not confounded by indication, since patients with indications for beta-blockers were excluded. It is likely the absence of more recent data supporting their use explains why some patients were not treated. The authors noted the use of beta-blockers declined during the 15-year study period from 92% to 67%.
There were other strengths, such as the inclusion of a positive control analysis of the association between statins and the primary outcomes, which showed significant reductions. Also, there was a negative control analysis of pneumonia where no association with beta-blocker use was shown. However, in observational studies, one can never completely exclude the influence of unmeasured confounders and selection biases. The authors believe their results should help inform future updates to the acute MI guidelines. For now, they recommend giving beta-blockers early after an MI to those without contraindications, but re-evaluate this use at three months.
- O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:e78-e140.