Valsartan in Acute Myocardial Infarction Trial ( VALIANT ) trial

• in this double-blind trial patients were randomized to optimal therapy with captopril (4909), valsartan (4909) in dosages up to 160 mg bid, or a combination of the two drugs (4885) within ten days of myocardial infarction complicated by left ventricular dysfunction or heart failure. Approximately 70% of patients were on beta blockers
  • in order to be included patients had to have clinical/ECG evidence and biomarker evidence of an acute myocardial infarct within the previous 10 days
    • also there was a requirement for clinical or radiological evidence of heart failure and/or left ventricular dysfunction (LVD) on the echocardiogram
      • clinical signs used to indicate heart failure were bilateral post-tussive rales in at least the lower third of lung fields or an S3 gallop with persistent tachycardia
  • patients were randomised into one of three groups
    • valsartan treatment alone (target dose 160mg twice a day), or,
    • captopril treatment alone (target dose 50mg three times a day), or,
    • a combination of captopril and valsartan (target doses 50mg three times a day and 80mg twice daily respectively)
    • doses were titrated up in four steps
      
      
• primary endpoint was all-cause mortality. The secondary endpoint was cardiovascular-related morbidity and mortality
  • there was no difference in mortality rates, which were approximately 20% for all three treatment groups
  • the rate of rehospitalization for myocardial infarction and heart failure approached 20% for all three groups
  • the valsartan-and-captopril group had the most drug-related adverse events
  • with monotherapy, 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 study authors concluded that Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Also combining valsartan with captopril increased the rate of adverse events without improving survival.This study also demonstrated that valsartan treatment resulted in a significantly lower level of treatment discontinuations due to adverse drug events in comparison to captopril treatment (1,2)
• a subsequent study (3) concluded that:
  • angiotensin receptor blockers appear to be as effective as ACE inhibitors in reducing atherosclerotic events, even when used in addition to other secondary preventive treatments
  • these data, although not conclusive, also support the hypothesis that adding an ARB to an ACE inhibitor may have a small additional anti-infarction effect, a possibility that needs to be prospectively tested

Reference:

1. N Engl J Med. 2003 Nov 13;349(20):1893-906. Epub 2003 Nov 10
2. Pfeffer MA, McMurray JJV, Velazquez EJ, et al. Valsartan, captopril or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. New Engl J Med 2003;349:1893-906.
3. McMurray J et al. The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). J Am Coll Cardiol 2006;47:726-33.