Lacidipine, hydrochlorothiazide and their combination in systolic hypertension in the elderly
Objective. To compare with placebo the efficacies of once-daily administrations of lacidipine and hydrochlorothiazide separately and in combination to elderly patients with systolic hypertension. Design and methods. Nineteen elderly subjects (five men and 14 women, median age 71 years, range 62-79 years) participated in the study, which had a randomized double-blind crossover design. For each subject there were four treatment phases, each of duration 4 weeks. The initial treatments in each phase were 2 mg lacidipine once a day and 25 mg hydrochlorothiazide once a day, separately and in combination, and placebo. Doses of each agent could be doubled after 2 weeks in each phase if the patient's goal systolic blood pressure had not been achieved. The numbers of subjects administered the higher dose of each treatment were 13 for placebo, 14 for lacidipine, 11 for hydrochlorothiazide and eight for lacidipine plus hydrochlorothiazide. Results. End-of-phase mean clinic blood pressures were 164/85 mmHg with placebo, 159/82 mmHg with lacidipine, 157/84 mmHg with hydrochlorothiazide and 152/82 mmHg with lacidipine plus hydrochlorothiazide. Systolic blood pressure was significantly reduced during all active treatment phases compared with placebo and that for the lacidipine plus hydrochlorothiazide phase was also significantly less than those for both of the other active treatment phases. There was no difference between sitting and standing blood pressure for any phase. Factorial analysis of the main effects of treatment indicated that the effects of lacidipine and hydrochlorothiazide on clinic blood pressure were additive and also that heart rate was higher when hydrochlorothiazide had been administered. Ambulatory blood pressure monitoring confirmed the pattern of the responses of blood pressure and showed that administration of hydrochlorothiazide had a significantly greater effect on systolic blood pressure and a longer duration of action than did administration of lacidipine. There was no difference in the frequency of adverse effects among any of the phases. Conclusions. In treating elderly systolic hypertensives the diuretic hydrochlorothiazide is a more effective antihypertensive agent with a longer duration of action than is the calcium channel antagonist lacidipine. In combination the effects of these two drugs on blood pressure are additive.