Journal Article

Effect on the development of ankle edema of adding delapril to manidipine in patients with mild to moderate essential hypertension: A three-way crossover study

Fogari, Elena, Fogari, Roberto, Mugellini, Amedeo, Malamani, GianDomenico, Perrone, Tiziano, Rinaldi, Andrea, Zoppi, Annalisa

2007

Overview

Use of the combination of an angiotensinconverting enzyme inhibitor (ACEI) and a calcium channel blocker (CCB) is considered a rational approach in patients whose hypertension is not controlled by monotherapy, providing better blood pressure (BP) control than the individual components with a lower incidence of adverse effects. In particular, such combinations have been found to reduce the incidence of ankle edema, the most common adverse effect of dihydropyridine annhypertensives. The present study was undertaken to evaluate the effect on the development of ankle edema of adding the ACEI delapril to the CCB manidipine in patients with mild to moderate essential hypertension. Patients between the ages of 30 and 70 years who had mild to moderate hypertension (diastolic BP [DBP] >90 and <110 mm Hg) were included in the study. After a 4-week placebo run-in period, eligible patients were randomized to receive 6 weeks each of manidipine 10 mg/d, delapril 30 mg/d, and both in a crossover fashion. There was a 2-week washout period between treatments. Ankle edema was assessed based on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP). Sitting BP, AFV, and PSTP were measured at the end of the placebo run-in period and the end of each active-treatment period. The study enrolled 40 patients with previously untreated hypertension (21 women, 19 men). Both manidipine and delapril monotherapy were associated with significant reductions from baseline in systolic BP (SBP) (mean [SD], -17.3 [4] and -14.8 [4] mm Hg, respectively; both, P < 0.01) and DBP (-14.6 [3] and -12.9 [3] mm Hg; both, P < 0.01). Compared with monotherapy, the combination of manidipine and delapril was associated with greater reductions from baseline in SBP (-21.8 [5] mm Hg; P < 0.001) and DBP (-18.6 [4] mm Hg; P < 0.001). Manidipme monotherapy was associated with significant increases from baseline in both AFV (7.9%; P < 0.001) and PSTP (36.6%; P < 0.01). Compared with manidipine alone, the combination of manidipine and delapril was associated with less pronounced increases in AFV (3.3%; P < 0.05) and PSTP (10.4%; P < 0.05). Ankle edema was clinically evident in 3 patients after receipt of manidipine monotherapy and in 1 patient after receipt of combination treatment. In these patients with mild to moderate essential hypertension, the addition of delapril to manidipine partially counteracted the manidipine-induced microcirculatory changes responsible for ankle edema.

• Publisher: EM Inc USA,Excerpta Medica,Elsevier Limited
• Subject: Adult / Aged / Angiotensin-Converting Enzyme Inhibitors - therapeutic use / Ankle - physiopathology / ankle edema / Antihypertensive Agents - adverse effects / Antihypertensive Agents - therapeutic use / Arterial hypertension. Arterial hypotension / Biological and medical sciences / Blood and lymphatic vessels / Calcium Channel Blockers - adverse effects / Calcium Channel Blockers - therapeutic use / Cardiology. Vascular system / combination treatment / Cross-Over Studies / delapril / Dihydropyridines - adverse effects / Dihydropyridines - therapeutic use / Drug Therapy, Combination / Edema - chemically induced / Edema - prevention & control / Female / Humans / Hypertension - drug therapy / Hypertension - physiopathology / Indans - therapeutic use / Internal Medicine / Male / manidipine / Medical Education / Medical sciences / Middle Aged / Pharmacology. Drug treatments / Treatment Outcome