Valsartan In Acute Myocardial Infarction Research Articles

Valsartan in Acute Myocardial Infarction Trial (VALIANT): Rationale and design

Background Survivors of acute myocardial infarction (MI) complicated by heart failure and/or resulting in left ventricular dysfunction are at heightened risk for subsequent death and major nonfatal cardiovascular events. Inhibition of the renin-angiotensin system with an angiotensin-converting enzyme inhibitor has consistently been demonstrated to result in reductions in these risks by approximately 20%. The development of angiotensin II receptor blockers offers a new, more specific, and theoretically more complete pharmacologic mode to inhibit the adverse influence of angiotensin II. Methods Valsartan in Acute Myocardial Infarction (VALIANT) is a multicenter, double-blind, randomized, active controlled parallel group study comparing the efficacy and safety of long-term treatment with valsartan, captopril, and their combination in high-risk patients after MI. The trial is designed with 3 arms, giving equal statistical consideration to survival comparisons of captopril versus the angiotensin II receptor blocker valsartan, as well as the combination of captopril plus valsartan, compared with a proven effective dose of captopril. This 14,500-patient trial is designed with an 86% power to detect a 15% reduction in mortality rate with either use of valsartan compared with captopril. The trial encourages optimal individualization of other proven therapies in acute and chronic infarction, and the international patient body ensures good representation of multiple practice patterns. Conclusion VALIANT is a large international investigative effort that will evaluate the role of valsartan in the management of patients with MI associated with heart failure and/or left ventricular dysfunction. The use of a proven dose of captopril and the comparator arms with valsartan alone or in combination with captopril provides a unique test of whether the angiotensin II receptor blocker can make an additional improvement in clinical outcomes beyond angiotensin-converting enzyme inhibitors. (Am Heart J 2000;140:727-34.)

Will more complete inhibition of the RAAS with angiotensin receptor blockade improve survival following myocardial infarction?

Angiotensin-converting enzyme (ACE) inhibitors have a well-established role in the management of patients with hypertension, diabetes, heart failure and myocardial infarction (MI). ACE inhibitors have been particularly well studied in acute and chronic MI with consistent and substantial survival benefits demonstrated, particularly in the higher risk groups. The recent development of angiotensin II (Ang II) receptor blockers (ARBs) as a well tolerated pharmacological therapy to more completely inhibit the actions of Ang II at the AT1-receptor level raises questions concerning comparative efficacy with the proven ACE inhibitor experience. Two major trials will provide a direct comparison of ARBs with an ACE inhibitor. The Valsartan in Acute Myocardial Infarction (VALIANT) trial is specifically designed to compare and contrast the ARB, valsartan, used both alone as well as in combination with a proven ACE inhibitor regimen, in a high risk MI population. VALIANT, with its three arms targetting 14,500 patients, is uniquely poised to determine whether the pharmacological advance in the development of ARBs confers additional clinical (survival) value in high risk MI patients.

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, β-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. (Am Heart J 2000;139:S23-S28.)