Do angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have similar effects in the improvement of left ventricular dysfunction after myocardial infarction in Japanese?

Hypertension increases the incidence of coronary artery disease (CAD). The first line of anti-hypertensive drugs should be selected from among calcium channel blockers, inhibitors of the renin-angiotensin system (RAS), diuretics and β-blockers (1). The inhibition of RAS with either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) has been shown to be beneficial for cardiovascular protection. More recently, ARBs have become available for use in patients who develop adverse events from ACEIs, and ARBs and ACEIs have been shown to be equally efficacious after myocardial infarction (MI). Two large-scale randomized clinical trials have been conducted to compare the usefulness of ARBs and ACEIs for secondary prevention in patients with MI (2, 3). In 2002, the Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan (OPTIMAAL) study indicated that there was no significant difference in all-cause mortality between treatment with the ACEI captopril and the ARB losartan after acute MI (2). However, losartan was better tolerated than captopril, and was associated with significantly fewer discontinuations. In this study, there was a problem in the choice of dose of losartan (50 mg/day). The Losartan Intervention For Endpoint reduction in hypertension (LIFE) (4) and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENNAL) (5) trials showed that losartan had beneficial effects when used at a dosage of 100 mg/day. In addition, the Valsartan in Acute Myocardial infarction (VALIANT) trial showed that the ARB valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after MI (3). With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group. The combination of valsartan with captopril increased the rate of adverse events without improving survival. These trials were performed mainly in Western countries, and there have been no studies on the effectiveness of ARBs in comparison to ACEI in the improvement of left ventricular (LV) dysfunction after MI in Japanese patients. Tani et al reported in Internal Medicine (6) that neither the ACEI enalapril nor losartan was superior to the other in terms of their effectiveness in preventing LV remodeling (ventricular dilatation, myocardial hypertrophy and interstitial fibrosis) after MI in Japanese patients. They randomly assigned 100 patients with anterior-wall MI who had received reperfusion therapy to treatment with either enalapril or losartan, and measured the LV ejection fraction and LV end-diastolic volume index at baseline and after 6 months of treatment (6). While their trial was in progress, Suzuki et al reported that valsartan is as effective as ACEI in preventing LV dysfunction in Japanese patients with acute MI (7). Although we now believe that ARBs and ACEI have similar effects in the improvement of LV dysfunction after acute MI in Japanese patients, there are pharmacological differences between ARBs and ACEIs. ACEIs can block the production of Ang II, but not completely. ARBs can directly block AT1 receptor-mediated signaling and may be more effective. Chymase is an important enzyme in the production of Ang II through a non-ACE-dependent pathway. The highest total Ang II-forming activity was observed in the heart, and a chymase-like enzyme was found to be dominant in humans (8). ARB increases the level of plasma Ang II, and Ang II may bind and activate AT2 receptor, which has beneficial ef-