Requiem for Beta-blockers Post-Myocardial Infarction?
By Michael H. Crawford, MD
Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco
Dr. Crawford reports no financial relationships relevant to this field of study.
SYNOPSIS: A propensity score analysis of all hospital survivors of acute myocardial infarction in the United Kingdom from 2007-2013 showed that one-year survival in hospital patients without heart failure or left ventricular dysfunction treated with beta-blockers did not differ from survival in those patients not so treated.
SOURCES: Dondo TB, Hall M, West RM, et al. Beta-blockers and mortality after acute myocardial infarction in patients without heart failure or ventricular dysfunction. J Am Coll Cardiol 2017;69:2710-2720.
Ibáñez B, Raposeiras-Roubin S, García-Ruiz JM. The swing of beta-blockers: Time for a system reboot. J Am Coll Cardiol 2017;69:2721-2724.
Controversy exists regarding the benefits of routine beta-blockers post-myocardial infarction (MI) in patients without heart failure or reduced left ventricular ejection fraction (LVEF) in the modern reperfusion era. Thus, investigators used the United Kingdom national heart attack register to determine their effect on one-year mortality for survivors of acute MI who were hospitalized and did not have LV systolic dysfunction (LVEF < 30%) or heart failure. This analysis involved 531,282 patients admitted to one of 247 hospitals between 2007 and 2013. After excluding those > 100 years of age, hospital deaths, those with prior MI, percutaneous coronary intervention, or coronary artery bypass grafting, heart failure, and those on a beta-blocker or loop diuretics, 179,810 remained. A propensity score analysis using a 24-variable model was used to adjust for potential confounders. Of the 91,895 with an ST segment elevation myocardial infarction (STEMI) and 87,915 with a non-STEMI, 95% were treated with beta-blockers. Patients given beta-blockers tended to be younger men, and those not receiving them more often were diabetic, asthmatic, or had chronic renal and cerebrovascular disease. In the total population during a maximum one-year follow-up, the mortality rate was 5%. This unadjusted rate was lower in those who received beta-blockers compared to those that did not (5% vs. 11%; P < 0.001). After propensity weighting and adjustment, there was no mortality difference between those on beta-blockers and those not at one month, six months, and one year. Also, this result was the same for STEMI and non-STEMI patients. The authors concluded that among hospital survivors of acute MI without heart failure or LVEF < 30%, one-year mortality was not different for those on beta-blockers vs. those who were not.
When the Beta-Blocker Heart Attack Trial (BHAT) first was published in 1982, I remember noting that in the subgroup analyses, the mortality benefit was strongest in those with evident heart failure on admission or a large anterior MI. Of course, subgroup analyses are not always accurate, and beta-blockers post-MI, supported by other studies, went on to be universally recommended. This even became a Medicare quality measure, but it was retired a few years ago when data emerged noting that the universal use of beta-blockers post-MI increased the risk of cardiogenic shock. Thus, over the years, we have chipped away at the recommendation, holding beta-blockers if the patient was bradycardic, hypotensive, or in acute heart failure.
The problem with BHAT and other similar randomized, controlled trials conducted in the 1980s is that they were conducted before we had available reperfusion therapy, statins, angiotensin-altering drugs, or antithrombotics other than aspirin. New trials in the current therapeutic milieu have not been performed, but we know that today there is less heart failure, reduced ejection fraction, and ventricular arrhythmias post-MI compared to the 1980s. Recent smaller observational studies have failed to demonstrate a survival benefit of routine beta-blocker use post-MI. This has occasioned the European Society of Cardiology guidelines to reduce this recommendation to class IIa. The American guidelines still list it as a class I recommendation.
This study from the United Kingdom was very large, involved current therapy at high levels, and used an unbiased source (all MIs). It demonstrated in propensity-matched patients that there is no difference in survival at any time over one year post-hospital discharge in all post-MI patients without heart failure or LVEF < 30% who received beta-blockers vs. those who did not. Despite the strengths of this study, there are weaknesses beyond the issue of residual conforming in any observational study. Since only hospital survivors were studied, the study did not address the acute in-hospital use of beta-blockers. Because of the potential for inducing cardiogenic shock, the American guideline no longer recommends routine acute intravenous beta-blockers. Also, heart failure and LVEF only were determined in the hospital, and we don’t know if beta-blockers were prescribed later. Additionally, we have no information on adherence to therapy or drug doses post discharge. Another issue brought up by the editorialists from Spain is that the LVEF exclusion of < 30% is lower than the < 40% used in most other studies. It could be that patients with EFs between 30% and 40-45% could benefit from beta-blockers. Thus, they suggested that a randomized trial be conducted using an LVEF cutoff of 40%.
The authors emphasized that recommending pharmacologic therapy that is not beneficial risks adverse effects, increases costs, and reduces the likelihood that patients will be compliant with other more effective medications. They suggested that the American guidelines should be rewritten. The editorialists, on the other hand, recommended “extreme caution” in enacting such a recommendation until a randomized trial is performed. Clearly, beta-blockers are indicated for selected patients in the hospital with acute MI, such as those with arrhythmias and hypertension, but should be given intravenously infrequently. At discharge, those with evidence of heart failure or a low EF will benefit from beta-blockers if there are no contraindications. The controversy surrounds those without heart failure, with preserved EF, normal blood pressure, and no arrhythmias. The European guidelines, supported by this paper, would say no. The U.S. guidelines would say yes. Since this is no longer a performance measure for Medicare, we are free to use our own judgment.
A propensity score analysis of all hospital survivors of acute myocardial infarction in the United Kingdom from 2007-2013 showed that one-year survival in hospital patients without heart failure or left ventricular dysfunction treated with beta-blockers did not differ from survival in those patients not so treated.
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