Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension

Background: Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension. We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events. In this post hoc analysis, we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients.

Methods: After stratification according to center, sex, and presence or absence of previous cardiovascular complications, 4695 patients (age, > or =60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were randomly assigned to receive active treatment or placebo. Active treatment consisted of nitrendipine (10 to 40 mg per day) with the possible addition or substitution of enalapril (5 to 20 mg per day) or hydrochlorothiazide (12.5 to 25 mg per day) or both, titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg. In the control group, matching placebo tablets were administered similarly.

Results: At randomization, 492 patients (10.5 percent) had diabetes. After a median follow-up of two years, the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg, respectively, among the diabetic patients. Among the 4203 patients without diabetes, systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg, respectively, in the two groups. After adjustment for possible confounders, active treatment was found to have reduced overall mortality by 55 percent (from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients), mortality from cardiovascular disease by 76 percent, all cardiovascular events combined by 69 percent, fatal and nonfatal strokes by 73 percent, and all cardiac events combined by 63 percent in the group of patients with diabetes. Among the nondiabetic patients, active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent. In the group of patients receiving active treatment, reductions in overall mortality, mortality from cardiovascular disease, and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients (P=0.04, P=0.02, and P=0.01, respectively).

Conclusions: Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension. Thus, our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients.