At the time of this trial, it was recognized that heart failure and LV systolic dysfunction after myocardial infarction (MI) was very prevalent and a major source of increased mortality. By this time, ACE inhibitors had clearly been shown to improve outcomes for these patients, but it was unknown if ARBs provided the same benefit. The OPTIMAAL (OPtimal Trial In Myocardial infarction with the Angiotensin II Antagonist Losartan) trial compared losartan to captopril with MI and evidence of heart failure or LV dysfunction. All-cause mortality was not significantly different between the two groups of patient’s, but due to the large confidence intervals, the criteria for noninferiority could not be established.
The main question is if among patients in the post-MI period complicated by HF and/or LV systolic dysfunction, what is the efficacy of ARBs compared with ACE-I in improving survival? This study enrolled 14,703 patients within 10 days of an MI that was complicated by heart failure or LV systolic dysfunction. Patients were randomized to captopril, valsartan, or captopril + valsartan. The primary endpoint was all cause mortality. Secondary endpoints were CV death, MI or HF. The optimal study was a similar trial studying captopril vs losartan, but due to large confidence intervals, non-inferiority could not be established and therefore, ACE inhibitors remained first choice. The trial aimed to established superiority of valsartan vs captopril and the superiority of the combination vs captopril alone. If superiority was not established, then noninferiortity would be examined. There was around 2yrs follow up. Valsartan was noninferior to captopril. The combination of captopril and valsartan was not superior, but did increase the rates of adverse events.
This study was an important study that helped us get to the point that we can substitute ARBs for ACE inhibitors for this particular situation and helped lead to the general interchangeability of these drugs based on further studies.
The VALIANT Trial: Pfeffer, M. A., McMurray, J. J., Velazquez, E. J., Rouleau, J. L., Køber, L., Maggioni, A. P., ... & Leimberger, J. D. (2003). Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. New England Journal of Medicine, 349(20), 1893-1906.
VALIANT Trial PMID: 12921816
Useful Summaries of the VALIANT Trial: Wiki Journal Club