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

Treatment of acute myocardial infarction (MI) has been advanced considerabl y in the past 20 years with the advent of acute reperfusion strategies such as thrombolytic therapy or primary angioplasty and the use of adjunctive m edical therapies such as aspirin, beta-blockers, and HMG-CoA reductase inhi bitors (statins); each has been proven to reduce morbidity and mortality ra tes after MI. Angiotensin-converting enzyme (ACE) inhibitors have earned an important place in this list of winners; particularly in patients clinical ly assessed as being at higher risk for cardiovascular death. The benefits of treating such patients with an ACE inhibitor have clearly shown signific ant improvements in survival thai are both complementary and additive to th e other proven therapies. However, a significant subset of patients treated with ACE inhibitors will die or have worsening congestive heart failure de spite adequate therapy. Appropriate risk stratification can help guide the clinician in identifying patients at greatest risk for cardiovascular event s after MI. Fortunately, investigators are currently exploring the potentia l benefits of more specific and selective blockade of the renin-angiotensin system with AT(1) receptor blockers (ARBs) in the hope of enhancing surviv al beyond that evidenced with ACE inhibition alone. These agents pharmacolo gically inhibit the renin-angiotensin system at the angiotensin (Ang) II ty pe 1 receptor level. Although there ore theories postulating why blocking t he harmful effects of Ang II at this receptor would be more effective than inhibiting ACE-mediated conversion from inactive Ang I to Ang ii, extrapola tion to the clinical setting remains highly speculative. These hypotheses c an only be tested by direct comparisons of ACE inhibitors and ARBs in the a ppropriate patient populations. The VALIANT (Valsartan in Acute Myocardial Infarction) trial is testing the hypothesis that interruption of the renin- angiotensin pathway by using the ARE valsartan alone or in combination with an ACE inhibitor will be more effective in saving lives than an ACE inhibi tor alone in heating patients at high risk. This trial will enroll patients with symptoms of congestive heart failure or depressed left ventricular ej ection fraction and randomly assign them to either captopril, valsartan, or the combination. Other proven conventional post-Mi therapies are encourage d. This study will definitively determine whether the use of valsartan offe rs additional benefits over those achieved with ACE inhibitor monotherapy i n patients at high risk after MI.