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ARB, ACE Inhibitor, or Both After MI in High-Risk Patients?

ACE inhibitors are well-established for limiting morbidity and mortality after MI, particularly in patients with LV dysfunction, heart failure, or both. To test the hypothesis that an angiotensin-receptor blocker (ARB), either alone or combined with an ACE inhibitor, is more effective than an ACE inhibitor alone in high-risk patients after MI, researchers conducted a manufacturer-funded randomized trial that compared precisely those 3 regimens.

A total of 14,703 adults with post-MI LV dysfunction or heart failure (mean ejection fraction, 35%) were randomized within 0.5 to 10 days of the index event to receive valsartan (target dosage, 160 mg twice daily); captopril (target dosage, 50 mg thrice daily); or both (target dosages: valsartan, 80 mg twice daily; captopril, 50 mg thrice daily). Standard post-MI therapies were encouraged; about half the patients underwent thrombolysis or percutaneous coronary intervention for the index MI.

During follow-up (median, 24.7 months), all-cause mortality incidence did not differ significantly among the 3 groups (range, 19.3%-19.9%). In an analysis to assess the noninferiority of valsartan, it was found to be equivalent to captopril for reducing all-cause mortality. Combined therapy had no additional benefit and was associated with a significantly higher incidence of adverse events (35%) than was either monotherapy regimen (28%-29%). Of the 3 groups, the 2 valsartan groups experienced the most hypotension and renal insufficiency, whereas the captopril-alone group experienced the most cough and rash.

Comment: At the specific dosages tested in high-risk post-MI patients in this study, valsartan was as effective as captopril for limiting all-cause mortality. However, the weight of previous clinical trial evidence, and the somewhat higher incidence of hypotension and renal insufficiency with valsartan in the present trial, support use of an ACE inhibitor as first-line therapy in high-risk post-MI patients. Combining an ACE inhibitor with an ARB should be discouraged in these patients. See Journal Watch Cardiology Dec 17 2004 for a review of a recent meta-analysis comparing ARBs and ACE inhibitors for heart failure and high-risk MI.

— William T. Abraham, MD

Published in Journal Watch Cardiology December 31, 2004

Citation(s):

Pfeffer MA et al for the Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003 Nov 13; 349:1893-906.

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• Medline abstract (Free)

Mann DL and Deswal A. Angiotensin-receptor blockade in acute myocardial infarction -- A matter of dose. N Engl J Med 2003 Nov 13; 349:1963-5.

• Original article (Subscription may be required)
• Medline abstract (Free)