Beta-Blockers for Acute Myocardial Infarction
Beta-Blockers for Acute Myocardial Infarction
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
Source: Chen ZM, et al. COMMIT Collaborative Group. Early Intravenous Then Oral Metoprolol in 45,852 Patients with Acute Myocardial Infarction: Randomised Placebo-Controlled Trial. Lancet. 2005;366:1622-1632.
The emergency treatment of patients with acute myocardial infarction (MI) with intravenous then oral beta-blockers has become the standard of care based upon randomized trials of over 27,000 patients. However, most of these trials were done before the advent of reperfusion therapy and aggressive platelet antagonists. Thus, the Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) studied the balance of risks vs the benefits of this aggressive beta-blocker strategy in acute MI treated by current methods. In over 45,000 patients admitted to 1250 hospitals within 24 hours of suspected acute MI, a 2 x 2 factorial trial of early beta-blockers or clopidogrel vs placebo plus aspirin was conducted. In 93%, ECG ST-elevation or new left bundle-branch block was present. The metoprolol protocol was up to 15 mg IV then 200 mg po daily until discharge or 4 weeks in the hospital. The primary outcome end points were: 1) death, reinfarction or cardiac arrest; 2) all-cause mortality, at first discharge or 28 days. No long-term therapy or follow-up was attempted, possibly because the study was done in China.
Results: Metoprolol did not reduce either primary end point (9.4% metoprolol, 9.9% placebo, and 7.7% metoprolol vs 7.8% placebo for death alone). However, metoprolol did decrease reinfarction (2% vs 2.5%; P = .001) and ventricular fibrillation (2.5% vs 3.0%; P = .001), but these positive effects were counterbalanced by an increase in cardiogenic shock (5% vs 4%; P < .001) during the first day after admission. Consequently, overall effects were adverse during the first day and then improved. Also, metoprolol increased the number of patients developing heart failure (14% vs 13%; P < .001) or non-shock hypotension (6% vs 3%; P < .001). Although bradycardia was more common with metoprolol, atrioventricular block was not. Not unexpectedly, metoprolol produced worse outcomes in hemodynamically unstable patients and no benefit in stable patients. Chen and colleagues concluded that beta-blockers should not be started until hemodynamic stability can be assured in acute MI patients.
Commentary
Despite several trials touting the benefits of early IV beta-blockers for acute MI there has been physician ambivalence about its use. Reportedly, use in the United Kingdom is less than 1%, and in Sweden, 54%. Many physicians have observed marked bradycardia and hypotension, and the appearance of signs of left heart failure after IV beta-blockers for acute MI. Also, during the era of widespread use of indwelling right heart catheters to manage acute MI (before revascularization); many were concerned about the almost universally observed increase in pulmonary capillary wedge capillary wedge pressures after IV beta-blockers. Such observations understandably lead to a more cautious approach to IV beta-blocker use among many physicians. In addition, many of us were puzzled by the push for IV beta-blocker use when earlier studies that started beta-blockers after 30 days post MI showed a strong benefit. The small gain of early administration seemed to be balanced by greater risks in the pre-reperfusion era, but the beta-blocker police persisted, as the acute MI care guidelines for several organizations can attest.
In the reperfusion era, it is perfectly reasonable to restudy this issue. This is the era of bringing blood to ischemic myocardium, not drugs after all. Low and behold, our old fears are justified; in this trial early IV beta-blockers caused net harm that was never overcome despite later benefits over one month of therapy. You could almost make the argument that they should be withheld for the first month, but Chen and colleagues concluded that they should be avoided in patients who showed early high-risk signs for developing cardiogenic shock such as, tachycardia, hypotension, or heart failure. Interestingly, there was no specific subgroup that always benefited from early beta-blocker use.
This study is larger than all previous trials by 2-fold, and has 3 times the number of deaths. Thus, it is a robust study of a wide spectrum of patients. The major limitation of the study is that it was done in China, and only thrombolytic reperfusion was used in a little over half the patients. Regardless, this study should temper the early aggressive beta-blocker proponents and support a more clinical judgment-based approach. Unfortunately, the latter is difficult to get into algorithms and guidelines, and doesn't lend itself well to quality improvement data gathering.
The emergency treatment of patients with acute myocardial infarction (MI) with intravenous then oral beta-blockers has become the standard of care based upon randomized trials of over 27,000 patients. However, most of these trials were done before the advent of reperfusion therapy and aggressive platelet antagonists.Subscribe Now for Access
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