Quantification of pedal edema during treatment with S(-)-amlodipine nicotinate versus amlodipine besylate in female Korean patients with mild to moderate hypertension: a 12-week, multicenter, randomized, double-blind, active-controlled, phase IV clinical trial

Abstract

Background: Amlodipine is a racemic mixture of (R)- and (S)-enantiomers. It has been suggested that removing the therapeutically inactive (R)-enantiomer will reduce adverse events while preserving the agent's efficacy. Women experience more adverse effects from amlodipine.

Objective: This exploratory study compared the amount of pedal edema experienced by female Korean patients with mild to moderate hypertension when receiving S(-)-amlodipine nicotinate compared with amlodipine besylate.

Methods: This study was a 12-week, multicenter, randomized, double-blind, active-controlled, Phase IV clinical trial. Female patients with mild to moderate hypertension were randomly assigned to receive either S(-)-amlodipine nicotinate 2.5 to 5 mg once daily or amlodipine besylate 5 to 10 mg once daily for 12 weeks. The primary objective was to compare the change in ankle-foot volume quantified by using a water displacement method after 12 weeks of therapy. The secondary objectives were to compare the changes in mean sitting systolic and diastolic blood pressures. Safety assessment included monitoring all laboratory tests, adverse events (AEs), serious AEs, and possible relation to the study medication.

Results: Of the 38 patients enrolled, 17 patients in each group were eligible for final analysis. In the S(-)-amlodipine nicotinate group, the mean ankle-foot volume at baseline was 1056.91 (98.15) mL, and volume after 12 weeks of treatment was 1016.68 (158.37) mL, a decrease of 40.24 (110.05) mL. In the amlodipine besylate group, mean ankle-foot volume at baseline was 1037.56 (158.30) mL, and volume after treatment was 1067.59 (152.54) mL, an increase of 30.03 (69.59) mL. There was a significant difference in the change of ankle-foot volume between the 2 groups (-70.26 mL [95% CI, -134.60 to -5.94], P = 0.028). After 12 weeks, the mean changes in sitting systolic blood pressure from baseline were not significantly different between the 2 groups (-21.82 [8.76] vs -26.82 [11.89] mm Hg; P = 0.172). Changes in mean sitting diastolic blood pressure also were not significant (-14.71 [6.94] vs -10.88 [5.81] mm Hg; P = 0.091). One patient in each group had facial edema, and another patient in the amlodipine besylate group had facial flushing. Overall, there was no significant difference in drug-related AEs between the 2 groups (P = 0.999).

Conclusions: These female Korean patients with hypertension taking S(-)-amlodipine nicotinate had less ankle edema, with no significant difference in BP-lowering efficacy, compared with those taking amlodipine besylate. S(-)-amlodipine nicotinate may be a suitable alternative for patients intolerant to amlodipine besylate. (Clinical Research Information Service: CRiS, KCT0000450).