Enalapril Suppresses Ventricular Remodeling More Effectively Than Losartan in Patients With Acute Myocardial Infarction

Hiroyuki Onodera, MD; Toshiro Matsunaga, MD; Yujin Tamura, MD; Naotaka Maeda, MD; Takumi Higuma, MD; Shingo Sasaki, MD; Yasuhiro Mori, MD; Fuminobu Yoshimachi, MD; Hiroshi Ishizaka, MD; Hiroyuki Hanada, MD; Tomohiro Osanai, MD; Ken Okumura, MD


Am Heart J. 2005;150(4):689.e11-689e.16. 

In This Article

Abstract and Introduction

Background: Ventricular remodeling after acute myocardial infarction (AMI) is associated with increased morbidity and mortality. ELITE II study showed that losartan, an angiotensin receptor blocker, shows a survival benefit to the same degree as captopril, an angiotensin-converting enzyme inhibitor, does in patients with heart failure. However, recent OPTIMAAL study showed that clinical outcomes after losartan are not superior to those after captopril in patients with AMI. We examined the effect of losartan on ventricular remodeling after AMI comparatively with that of enalapril.
Methods: We enrolled 203 consecutive patients with AMI (mean age 62 ± 11 years). All patients underwent primary percutaneous coronary intervention and were randomly assigned to losartan (25-50 mg, n = 101) or enalapril (2.5-10 mg, n = 102) treatment. Biplane left ventriculography was performed just after primary percutaneous transluminal coronary angioplasty (acute phase) and 6 months after the onset of AMI.
Results: Any of the maximal creatine kinase level, left ventricular end-diastolic volume index, end-systolic volume index, and ejection fraction measured at acute phase was not different between losartan and enalapril groups. However, changes in left ventricular end-diastolic index (18 ± 25 vs 8 ± 24 mL/m2) and left ventricular end-systolic volume index (10 ± 20 vs 2 ± 18 mL/m2) from acute phase to 6 months were significantly greater in losartan than in enalapril group. Change in left ventricular ejection fraction (0.2% ± 10.3% vs 3.4% ± 11.6%) from acute phase to 6 months was significantly smaller in losartan than in enalapril group. The plasma level of brain natriuretic peptide at 6 months was significantly higher in losartan than in enalapril group (all P < .05).
Conclusion: These indicate that enalapril suppresses ventricular remodeling after AMI more effectively than losartan.

The progressive left ventricular enlargement after acute myocardial infarction (AMI), that is, ventricular remodeling, causes pump dysfunction and increases incidences of mortality and morbidity.[1,2,3] It has been reported that cardiac renin-angiotensin system is activated after AMI and is involved in the pathophysiology of ventricular remodeling.[4,5] Many clinical studies demonstrated that angiotensin-converting enzyme (ACE) inhibitors (ACEIs) attenuate ventricular remodeling and decrease the mortality and morbidity of patients with AMI.[1,2,3] Angiotensin type 1 receptor blockers (ARBs), another type of inhibitor of renin-angiotensin system, induce a more complete blockage of angiotensin II produced by ACE and chymase.[6,7] The validity of ARB in patients with heart failure was shown in the Val-HeFT and the CHARM studies.[8,9] However, these studies were designed to compare between ARB and placebo treatments, or between ARB plus ACEI treatment and ACEI treatment. The ELITE II study, which compared ACEI and ARB in heart failure, did not reveal significant difference in all-cause mortality between captopril and losartan.[10] More recently, the OPTIMAAL showed that the incidence of cardiovascular death was greater in losartan group than in captopril group.[11] Consequently, it is not concluded which drug, ARB or ACEI, is beneficial for the treatment in patients with AMI. We hypothesized that there is a difference in the effect on the development of ventricular remodeling after AMI between ARB and ACEI treatments. To test this, we examined comparatively the effects of losartan and enalapril on left ventricular remodeling and plasma BNP level after AMI.