New angiotensin receptor blocker is as effective as ACE inhibitorBMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7424.1123-a (Published 13 November 2003) Cite this as: BMJ 2003;327:1123
An angiotensin receptor blocker is as effective as an angiotensin converting enzyme (ACE) inhibitor in patients who are at high risk of cardiovascular events after myocardial infarction. But combining the two drugs seems to increase the rate of adverse events without improving survival.
ACE inhibitors reduce mortality and cardiovascular morbidity among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. In a double blind trial known as the Valiant study, researchers led by Dr Marc Pfeffer, professor of cardiology at the Brigham and Women's Hospital in Boston, Massachusetts, compared the effect of the angiotensin receptor blocker valsartan, the ACE inhibitor captopril, and a combination of the two on mortality in this population of patients (New England Journal of Medicine 2003;349: 1893-906).
In the randomised, double blind trial, patients at 931 centres in 24 countries who were receiving conventional treatment were randomly assigned (0.5 to 10 days after acute myocardial infarction) to additional treatment with valsartan (4909 patients), valsartan plus captopril (4885), or captopril alone (4909). The primary end point was death from any cause.
During a median follow up of 24.7 months, 979 patients in the group taking valsartan died, as did 941 patients taking valsartan plus captopril and 958 patients taking captopril alone (compared with the captopril group, hazard ratios were 1.00 (97.5% confidence interval, 0.90 to 1.11; P=0.98 in the valsartan group and 0.98 (0.89 to 1.09; P=0.73) in the valsartan plus captopril group).
The participants taking valsartan plus captopril had the most drug related adverse events. Comparing valsartan alone with captopril alone, the researchers found that hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group.
The combination of valsartan plus captopril was evaluated to determine whether incremental clinical benefits could be achieved with two inhibitors of the renin-angiotensin system. But in the current study, this combination did not reduce mortality or the rates of key secondary outcomes in the patients studied, despite additional lowering of blood pressure and a clear increase in the rate of intolerance to treatment.
This finding contradicts the findings from two recent trials of patients with heart failure that showed improvements in cardiovascular outcomes with the addition of an angiotensin receptor blocker to conventional treatment that included an ACE inhibitor (New England Journal of Medicine 2001;345: 1667-75, Lancet 2003;362: 767-71Lancet 2003;362: 759-66.)
“Given that valsartan was as effective as captopril in reducing the rates of death and other adverse cardiovascular outcomes among patients who had had a myocardial infarction, it should be considered a clinically effective alternative,” the authors wrote in the latest paper.