Effects of Candesartan on Cardiovascular Outcomes in Japanese Hypertensive Patients

Abstract

In recent years, angiotensin receptor blockers (ARBs) have begun to represent a markedly larger percentage of the antihypertensive agents used in Japan. However, it remains uncertain whether ARBs are effective for protecting against hypertension-related organ damage in the general Japanese population. In the present report, we describe the results of a single blind, randomized, prospective study conducted in 1999-2002 and employing a total of 2,048 essential hypertensive subjects (sitting blood pressure 140-180/90-110 mmHg) aged 35-79 years. Subjects were randomly assigned to receive the ARB candesartan, 2 to 12 mg daily, or conventional antihypertensive drugs other than angiotensin converting enzyme inhibitors or ARBs. We used Cox regression analysis to compare the two regimens. The primary outcome was assessed by hospitalization due to stroke, myocardial infarction, and congestive heart failure. Blood pressure was reduced from 162.1/91.1 to 140.1/78.9 mmHg in the candesartan group and from 165.9/95.9 to 138.4/81.1 mmHg in the conventional therapy group. The main outcomes were as follows: there was a 39% reduction in hospitalization for stroke (5.8 vs. 9.4 cases: relative risk [RR]: 0.61; 95% confidence interval [CI]: 0.41-0.84; p<0.05) and a 57% reduction in hospitalization for myocardial infarction (RR: 0.44; CI: 0.21-0.84; p<0.05) with the candesartan-based treatment compared with the conventional treatment. In spite of a significant difference in the total incidence of both stroke and myocardial infarction, there was no significant reduction in the incidence of congestive heart failure (15% reduction: 4.3 vs. 5.0; RR: 0.85; CI: 0.57-1.26). Further analysis in stratifying the subjects with or without a past history of cardiovascular diseases including stroke and myocardial infarction revealed that candesartan reduced the incidence of stroke (61% reduction; RR: 0.39; CI: 0.15-0.43; p<0.01) and congestive heart failure (49% reduction; RR: 0.51; CI: 0.23-0.92; p<0.05) but not myocardial infarction (RR: 0.74; CI: 0.36-1.48; p=0.1) in hypertensive patients with a past history. However, conventional treatment was superior to candesartan-based treatment in reducing the incidence of stroke in the patients without a past history of cardiovascular diseases (66% reduction; RR: 0.34; CI: 0.16-0.69; p<0.05). This is the first demonstration that an ARB-based antihypertensive treatment was superior to the conventional treatment for reducing the risk of stroke and myocardial infarction in Japanese hypertensive patients, especially in the patients with a past history of cardiovascular diseases.