Enhancing cardiac protection after myocardial infarction: rationale for newer clinical trials of angiotensin receptor blockers.

Treatment of acute myocardial infarction (MI) has been advanced considerably in the past 20 years with the advent of acute reperfusion strategies such as thrombolytic therapy or primary angioplasty and the use of adjunctive medical therapies such as aspirin, beta-blockers, and HMG-CoA reductase inhibitors (statins); each has been proven to reduce morbidity and mortality rates after MI. Angiotensin-converting enzyme (ACE) inhibitors have earned an important place in this list of winners, particularly in patients clinically assessed as being at higher risk for cardiovascular death. The benefits of treating such patients with an ACE inhibitor have clearly shown significant improvements in survival that are both complementary and additive to the other proven therapies. However, a significant subset of patients treated with ACE inhibitors will die or have worsening congestive heart failure despite adequate therapy. Appropriate risk stratification can help guide the clinician in identifying patients at greatest risk for cardiovascular events after MI. Fortunately, investigators are currently exploring the potential benefits of more specific and selective blockade of the renin-angiotensin system with AT(1) receptor blockers (ARBs) in the hope of enhancing survival beyond that evidenced with ACE inhibition alone. These agents pharmacologically inhibit the renin-angiotensin system at the angiotensin (Ang) II type 1 receptor level. Although there are theories postulating why blocking the harmful effects of Ang II at this receptor would be more effective than inhibiting ACE-mediated conversion from inactive Ang I to Ang II, extrapolation to the clinical setting remains highly speculative. These hypotheses can only be tested by direct comparisons of ACE inhibitors and ARBs in the appropriate patient populations. The VALIANT (Valsartan in Acute Myocardial Infarction) trial is testing the hypothesis that interruption of the renin-angiotensin pathway by using the ARB valsartan alone or in combination with an ACE inhibitor will be more effective in saving lives than an ACE inhibitor alone in treating patients at high risk. This trial will enroll patients with symptoms of congestive heart failure or depressed left ventricular ejection fraction and randomly assign them to either captopril, valsartan, or the combination. Other proven conventional post-MI therapies are encouraged. This study will definitively determine whether the use of valsartan offers additional benefits over those achieved with ACE inhibitor monotherapy in patients at high risk after MI.