Double-Blind Studies of Calcium Antagonists in the Treatment of Hypertension in Japan

Japanese studies of six calcium antagonists are reviewed, and the antihypertensive response to these drugs is analyzed in groups of young, middle-aged, and old subjects. The phase III clinical trials were performed in double-blind group studies that compared the calcium antagonist with a standard drug. In accordance with the guidelines for the clinical evaluation of antihypertensive agents, patients with a blood pressure level greater than or equal to 160/95 mm Hg after receiving a placebo for 4 weeks were enrolled in the study. The test drug was then administered for 12 weeks. A decrease in blood pressure by 20/10 mm Hg from the pretreatment level or a blood pressure level below 149/89 mm Hg was considered to indicate a response. The response rates for nicardipine, diltiazem, nifedipine tablets, long-acting nicardipine, nilvadipine, and nitrendipine were 64.6, 67.4, 68.6, 69.7, 70.7, and 65.9%, respectively. The average pretreatment blood pressure level was 170-175/100 mm Hg, and the average decrease in blood pressure was about 25/14 mm Hg. The reproducibility of the response rate of nicardipine used as a standard drug was shown in four different double-blind studies, where the response rate ranged from 65 to 72%. Side effects were observed in 8-18% of subjects, and the rate of side effects was also found to be reproducible in nicardipine studies. In severe hypertension unresponsive to diuretics and beta-blockers, response rates ranged from 79 to 93%. The antihypertensive response to calcium antagonists was not related to age, but correlated with the pretreatment blood pressure level. Therefore, calcium antagonists are effective and useful in treating mild, moderate, and severe hypertension in patients of all ages.