Pinacidil and hydrochlorothiazide alone or in combination in the treatment of hypertension in the elderly

Abstract

Pinacidil (PIN) is a new antihypertensive cyanoguanidine derivative compound classified as a potassium channel opener. This double-masked, randomized, controlled clinical study compared the antihypertensive efficacy of PIN 25 mg alone, hydrochlorothiazide (HCTZ) 12.5 mg alone, and PIN 12.5 mg + HCTZ 12.5 mg, all given once a day. Eighty-four elderly outpatients (39 men, 45 women; mean age, 77.5 ± 5.5 years) with mild or moderate hypertension (diastolic blood pressure between 95 and 115 mm Hg) were randomly assigned to one of the three treatment groups. After a 3-week placebo run-in period, patients received the active drug at 8 am daily for 8 weeks. Office blood pressure (BP) measurements were performed at baseline and at 1, 2, 4, and 8 weeks. Ambulatory BP monitoring (ABPM) was performed for 24 hours (from 7 am to 7 am of the next day) at baseline and at the end of the treatment period. At the end of 8 weeks, 62 patients (73.8%) had normal BP (20 patients [71.4%] treated with PIN, 19 patients [67.9%] treated with HCTZ, and 23 patients [82.1%] treated with PIN + HCTZ). The classification of the patients as responders or nonresponders showed that all three treatments were effective, with a slight advantage for the combination therapy (26 responders [92.8%]) over HCTZ alone (24 responders [85.7%]) and PIN alone (22 responders [78.6%]). However, differences between the groups were not significant. Ambulatory BPs were significantly reduced in all groups. Patients receiving HCTZ alone and PIN + HCTZ achieved good BP control that was persistent over the 24 hours, whereas patients receiving PIN alone failed to achieve a significant reduction in nighttime BP. Heart rate was reduced in patients in the HCTZ and PIN + HCTZ groups (7.2% and 5.7%, respectively), whereas it was only slightly changed in patients in the PIN group (1.4%). All drug regimens were well tolerated; only 11 patients complained of mild or moderate side effects, and on patient discontinued treatment. In conclusion, combination therapy with PIN 12.5 mg + HCTZ 12.5 mg, given once a day, appears to provide effective and well-tolerated 24-hour BP control in elderly hypertensive patients.