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Abstract & Commentary
Synopsis: The angiotensin II antagonist valsartan, at 320 mg per day, is as effective as captopril at 150 mg per day in reducing mortality in these high-risk patients. The combination of both drugs adds side effects without benefit.
Source: Pfeffer MA, et al. N Engl J Med. 2003;349:1893-1906.
Previous research failed to show that the angiotensin II antagonist losartan at 50 mg per day was as effective as captopril in reducing mortality in patients with heart failure after myocardial infarction.1 This raised the question of whether this new class of drugs may be substituted for ACE inhibitors in treating these high-risk patients. Both classes of drugs block the angiotensin pathway and would be expected to confer similar benefits.
This study compared the angiotensin II antagonist valsartan with captopril. Higher doses of the angiotensin II antagonist were used. More than 14,000 patients were randomized after myocardial infarction to receive valsartan at 160 mg twice daily, captopril 50 mg 3 times daily, or both. All patients had left ventricular dysfunction or heart failure. There was no placebo group, but the protective benefit of captopril at this dose over placebo has been demonstrated. The mortality over a median follow-up of 24.7 months was the same for both drugs. There was no increased benefit, but greater drug side effects, from using the combination. Patients taking valsartan had more hypotension and renal dysfunction, and patients taking captopril had more cough, rash, and taste disturbance.
Comment by Joseph E. Scherger, MD, MPH
This study clarifies a role for angiotensin II antagonists as an alternative to an ACE inhibitor for treating patients with heart failure after myocardial infarction. As the editorial by Mann and Deswal in this same issue states, dosage is important.2 The angiotensin II antagonist valsartan, taken at 320 mg per day, may be substituted for a full dose ACE inhibitor. ACE inhibitors remain a first choice due to their lower cost and less serious side effects. However, some patients simply cannot tolerate an ACE inhibitor, usually due to a protracted cough or allergic reaction. In this day of multiple drug use for cardiac disease, it is good to know that using both drugs in combination does not confer added benefit.
1. Dickstein K, et al. Lancet. 2002;360:752-760.
2. Mann DL, et al. N Engl J Med. 2002;349:1963-1964.
Dr. Scherger is Clinical Professor, University of California, San Diego.