Pilot study to evaluate a water displacement technique to compare effects of diuretics and ACE inhibitors to alleviate lower extremity edema due to dihydropyridine calcium antagonists

Combination therapy is required in many patients to achieve goal blood pres sure (BP). Calcium antagonists are highly effective antihypertensive drugs in a broad range of demographic groups. Yet, higher doses are associated wi th an increased frequency of lower extremity edema. The purpose of our open label, single-center clinical trial was to evaluate the use of concomitant pharmacologic therapies to attenuate the lower extremity edema associated with dihydropyridine calcium antagonists therapy using a water displacement technique. Forty-seven patients received 5 mg/day of oral amlodipine for a period of 6 weeks after a 4-week wash-out off of all antihypertensive medi cations to establish baseline BP. They were then randomized to receive eith er an additional 5 mg of amlodipine, 25 mg of hydrochlorothiazide (HCTZ), o r 20 mg of benazepril for an additional 6 weeks. Blood pressure determinati ons and water displacement measurements were obtained at the end of the 4-w eek placebo wash-out period, after 6 weeks of 5 mg/day of oral amlodipine t herapy, and after an additional 6 weeks of 5 mg of amlodipine and randomize d drug therapy. Adjusted BP reductions (based on pretreatment BP) were -6.8 /-3.8 mm Hg for the 10-mg amlodipine group, -9.9/-8.2 mm Hg for the amlodip ine (5 mg)/HCTZ (25 mg) group, and -26.2/-16.4 mm Hg for the amlodipine (5 mg)/benazepril (20 mg) group (P < .0167, group 3 v group 1 diastolic BP, wh ich was statistically significant by the improved Bonferroni method). Seven teen of the 47 patients developed at least a 10% increase in lower extremit y edema water displacement in response to 5 mg/day of oral amlodipine thera py (36.2%). Adding 5 mg of amlodipine to a baseline of 5 mg of amlodipine r esulted in no net change in lower extremity edema (+58.0 mL, +0.6% change, n = 5). Adding 25 mg of HCTZ reduced lower extremity edema by a mean of 136 .3 mL (-11.1% change, n = 4). Benazepril reduced water displacement by 204. 4 mL (-14.3% change, n = 8). Our pilot study indicates that adding an angio tensin converting enzyme inhibitor to a dihydropyridine calcium channel blo cker is the most effective way to not only reduce systolic and diastolic BP but also attenuate lower extremity edema. Due to the inherent daily variab ility of lower extremity edema, power calculations indicate many patients ( n = 702, 356 in each group) would be needed to compare the antiedema effica cy of the angiotensin converting enzyme inhibitor and the thiazide diuretic . Am J Hypertens 2001; 14:963-968 (C) 2001 American Journal of Hypertension , Ltd.