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Abstract & Commentary
Source: Pfeffer MA, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349: 1893-1906.
Studies demonstrate that angiotensin-converting-enzyme (ACE) inhibitors such as captopril reduce mortality and cardiovascular morbidity for patients with myocardial infarction (MI) complicated by left ventricular systolic dysfunction, heart failure, or both. The authors surmised that since angiotensin II can be generated despite ACE inhibition, further efficacy can be obtained if receptor antagonists are combined with ACE inhibitors. The study was a randomized, double-blind trial conducted at 931 centers in 24 countries. Patients were considered for the study if they had an MI and either radiologic signs of heart failure or evidence of left ventricular systolic dysfunction (an ejection fraction < 0.35 on echocardiography or contrast angiography and £ 0.40 on radionuclide ventriculography). Patients were excluded if they had a systolic blood pressure lower than 100 mmHg or a serum creatinine concentration of more than 2.5 mg/dL.
Patients randomly were assigned, from 12 hours to 10 days after acute MI, to valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (4909 patients). Therapy was begun with either 20 mg of valsartan, 20 mg of valsartan plus 6.25 mg of captopril, or 6.25 mg of captopril (increased gradually). The primary end point was death from any cause. During a median follow-up of two years, slightly fewer than 1000 patients died in each arm of the trial. Furthermore, no difference was seen in death from cardiovascular events, recurrent MI, or hospitalization for heart failure. The valsartan-and-captopril group had the most drug-related adverse events. Hypotension and renal dysfunction were more common in the valsartan only group, and cough, rash, and taste disturbance were more common in the captopril group. The authors conclude that valsartan is as effective as captopril in preventing death after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival.
Commentary by Richard J. Hamilton, MD, FAAEM, ABMT
This study, designed to determine if valsartan offered an advantage over captopril in patients with heart failure after MI, found no difference. In addition, combination therapy only added to the adverse effect profile. Interestingly, that adverse effect profile may have been one of the more useful findings in this study. Patients who received captopril had less hypotension and renal dysfunction, although the annoying cough, rash, and taste disturbance side effects were slightly more common. Angioedema occurred with equal frequency in both groups. Couple this information with the knowledge that the retail price of 90 days of therapy with valsartan (320 mg QD) is $240, while 90 days of therapy with generic captopril (50 mg TID) is $40, according to drugstore.com. Perhaps this study ought to make us suspect that valsartan has little to offer most MI/heart failure patients over an ACE inhibitor. The exception may be for the 5% or fewer with the side effect of cough.
Dr. Hamilton, Associate Professor of Emergency Medicine, Residency Program Director, Department of Emergency Medicine, Drexel University College of Medicine, Philadelphia, PA, is on the Editorial Board of Emergency Medicine Alert.