Inhibitory Effect of Valsartan Against Progression of Left Ventricular Dysfunction After Myocardial Infarction

Abstract

Circ J 2009; 73: 918 -924 dvances in coronary care and coronary interventional therapies have reduced the in-hospital mortality rate to less than 10% 1 and improved myocardial remodeling in cases of acute myocardial infarction (AMI). 2 However, AMI patients successfully treated by coronary interventions within a few hours of the onset sometimes develop severe myocardial dysfunction in the chronic stage as a result of myocardial remodeling. Left ventricular (LV) remodeling after AMI limits the long-term prognosis of these patients and remains an important predictor of mortality. 3,4 Therefore, research to discover novel therapeutic strategies for limiting LV remodeling and preventing heart failure is very important. Editorial p 820Angiotensin-converting enzyme inhibitors (ACEI) have been shown in randomized trials to reduce the morbidity and improve survival in chronic heart failure and post-AMI patients, especially in selected high-risk patients. 5 Enalapril treatment initiated soon after the occurrence of myocardial infarction (MI) and continued for 6 months was shown to attenuate LV dilatation and produce a greater reduction in the LV volume as compared with placebo treatment after 1 month and 6 months of the occurrence of MI in a substudy of the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II) using echocardiography. 6 However, ACEI do not completely block the production of angiotensin II, therefore, it is considered that direct receptor blockade might be more effective. Blockade of angiotensin II via a non-ACE-dependent pathway through chymase has also been shown to be important in humans. 7 Incomplete inhibition of angiotensin II production by ACEI has been reported with low-dose and long-term treatment. 8 Therefore, use of angiotensin receptor blockers (ARB) might represent a (Received October 16, 2008; revised manuscript received December 24, 2008; accepted December 25, 2008; released Background: Angiotensin-converting enzyme inhibitors (ACEI) reduce the mortality in the chronic phase of myocardial infarction (MI), and similar effects of angiotensin receptor blockers (ARB) have been reported. However, these effects of ARB have not yet been established in Japanese patients. A multicenter randomized study was designed for the present study to examine the effect of valsartan as compared to that of ACEI against left ventricular dysfunction after MI. Methods and Results:Patients with acute MI were randomly allocated to either the valsartan group (n=120; mean age 63±1.0) or the ACEI group (n=121; mean age 62.9±1.0) and followed up until 6 months. Left ventriculography was performed during hospital admission and at 6 months. The blood pressure was similar in the 2 groups throughout the study. The incidences of cardiovascular events and target vessel revascularization were similar, although that of adverse events was significantly higher in the ACEI (12.4%) than in the valsartan group (3.3%; P<0.05). There were no differences in left ventricular ejection fraction and left ventricular en...

Relationship Between Beta-Blocker and Angiotensin-Converting Enzyme Inhibitor Dose and Clinical Outcome Following Acute Myocardial Infarction

“…20-22 Similar effects of angiotensin receptor blockers have been reported, particularly with the use of valsartan. 23 In-hospital heart failure was also an independent factor associated with in-hospital mortality; it is possible that the effect of absence of BB prescription on the day of admission on in-hospital mortality is explained in part by worse clinical status at admission, particularly heart failure, which limits treatment with BB. Another relevant finding of the present study was that few patients were at target dose at the time of discharge from hospital, with only 34.8% at target for BB, and 21.7% for ACEI.…”

Changes of Matrix Metalloproteinase-9 Level Is Associated With Left Ventricular Remodeling Following Acute Myocardial Infarction Among Patients Treated With Trandolapril, Valsartan or Both

“…Such ability to prevent ventricular remodeling after AMI has historically been demonstrated mainly in ACE inhibitors, but recent studies have revealed that ARBs are not inferior in this respect. 20 ACE inhibitors do not inhibit angiotensin II, which is produced via an ACEindependent pathway, but can enhance bradykinin accumulation, which results in increased endothelial NO production. ARBs prevent angiotensin II from directly binding to the angiotensin II type-1 receptor.…”

How Is Combination Therapy With ACEI and ARB Applied in Patients With Acute Myocardial Infarction?

“…The T-VENTURE Study demonstrated similar effects in the prevention of LV remodeling and clinical events between valsartan and ACEIs in Japanese patients with AMI. 8 In this issue of the Journal, Miyazaki et al have expanded the previous study by prospectively demonstrating that combination therapy with valsartan and trandolapril inhibited LV remodeling compared to monotherapy with either drug in Japanese patients with AMI. 9 This new evidence may be informative for Japanese cardiologists, but we have to stop and consider whether we are allowed to simply conclude that the combination therapy is effective in Japanese patients with AMI.…”