Comparative effect of lercanidipine and nifedipine gastrointestinal therapeutic system on ankle volume and subcutaneous interstitial pressure in hypertensive patients: A double-blind, randomized, parallel-group study

Background: Ankle edema is one of the most common side effects of antihypertensive treatment with calcium channel blockers (CCBs). The incidence of edema is higher with dihydropyridines than with verapamil or diltiazem. Objective: The aim of this study was to compare the effect of antihypertensive treatment with the new CCB lercanidipine versus nifedipine gastrointestinal therapeutic system (GITS) on ankle-foot volume (AFV) and on pretibial subcutaneous tissue pressure (PSTP), considered objective measures of CCB-induced ankle edema. Methods: Patients with mild to moderate hypertension (diastolic >90 mm Hg and <110 mm Hg) were studied. After a 4-week placebo run-in period, patients were treated with lercanidipine 10 mg once daily or nifedipine GITS 30 mg once daily for 12 weeks according to a randomized, double-blind, parallel-group design. At the end of the placebo and active-treatment periods, blood pressure (BP), heart rate, body weight, AFV, and PSTP were measured. AFV was measured using the principle of water displacement: the immersion of the foot and ankle into a given quantity of water causes water displacement equivalent to the immersed volume. This water was collected and measured. PSTP was assessed directly using a balancing open system consisting of a graduated capillary tube filled with saline solution and capped with a needle. When the needle is threaded into the subcutaneous pretibial tissue the system becomes closed. It is then connected to a water manometer where the PSTP is measured. Results: Sixty patients (34 men and 26 women) aged 36 to 70 years were enrolled. Lercanidipine and nifedipine GITS produced similar reductions in systolic and diastolic BP (lercanidipine, -18.7/11.8 mm Hg; nifedipine GITS, -18.8/11.5 mm Hg; P < 0.001 vs placebo). Both drugs significantly increased AFV and PSTP compared with placebo. However, lercanidipine produced a significantly less pronounced (P < 0.001) increase in AFV (143.6 mt) and PSTP (0.9 cm H2O) compared with nifedipine GITS (AFV, 284.2 mt; PSTP, 1.8 cm H2O). In both treatment groups, correlation analysis showed an inverse relationship, although to a different degree, between AFV and PSTP changes, but not between absolute values of AFV and PSTP during treatment. AFV increase was greater and PSTP increase was lower with increasing age, which suggests a role for age in the type of tissue response to a stimulus for edema formation. No relationship was found between AFV and PSTP changes and BP reduction. Conclusions: These data suggest that lercanidipine produces significantly less increases in AFV and PSTP, 2 objective measures of edema formation, than nifedipine GITS.