Effect of aliskiren addition to amlodipine on ankle edema in hypertensive patients: a three-way crossover study

The aim of this study was to assess the effect of aliskiren and amlopidine on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP).After 4-week placebo, 120 outpatients with grade 1 - 2 hypertension were randomized to amlodipine 10 mg or aliskiren 300 mg or their combination for 8 weeks in three crossover periods. At the end of each treatment, blood pressure, AFV, PSTP, plasma renin activity (PRA) and norepinephrine were assessed.Both monotherapies similarly reduced systolic blood pressure (SBP; p < 0.001) and diastolic blood pressure (DBP; p < 0.001), but the reduction was greater with amlodipine/aliskiren combination (SBP: - 24.6 mmHg, p < 0.001 vs monotherapy; DBP: -20.9 mmHg, p < 0.01 vs monotherapy). Amlodipine increased both AFV (+ 28.4\%, p < 0.01) and PSTP (+ 80.4\%, p < 0.01), while the combination produced a less marked increase in AFV (+ 6.6\%, p < 0.01 vs amlodipine) and PSTP (+ 20.1\%, p < 0.01 vs amlodipine). Plasma norepinephrine increased with amlodipine (+ 53.5\%, p < 0.01) and this increase was not reduced by aliskiren addition. PRA was unaffected by amlodipine, while it was reduced by both aliskiren monotherapy (- 77.7\%, p < 0.01) and aliskiren/amlodipine combination (- 75.7\%, p < 0.01).Direct renin inhibition by aliskiren partially counteracts the microcirculatory changes responsible for calcium-channel-induced edema formation, possibly through preferential vasodilation of venous capacitance vessels.