Combination therapy with lercanidipine and enalapril reduced central blood pressure augmentation in hypertensive patients with metabolic syndrome

Abstract

Arterial stiffness and blood pressure (BP) augmentation are independent predictors of cardiovascular events. In a randomized, open, parallel group study we compared the effect on these parameters of combination therapy with an ACE-inhibitor plus calcium channel blocker or thiazide diuretic in 76 hypertensive patients with metabolic syndrome uncontrolled by ACE-inhibitor monotherapy. After 4weeks run-in with enalapril (ENA, 20mg), patients were randomized to a combination therapy with lercanidipine (LER, 10-20mg) or hydrochlorothiazide (HCT, 12.5-25mg) for 24weeks. Aortic stiffness (carotid to femoral pulse wave velocity, PWV), central BP values and augmentation (augmentation index, AIx) were measured by applanation tonometry. The two groups showed similar office and central BP after run-in. Office (ENA/LER: from 149.1±4.9/94.5±1.5 to 131.7±8.1/82.2±5.3; ENA/HCT: from 150.3±4.7/94.7±2.1 to 133.1±7.1/82.8±5.3mmHg) and central BP (ENA/LER 127.4±17.1/85.2±12.1 to 120.5±13.5/80.0±9.5mmHg; ENA/HCT 121.6±13.4/79.3±9.5mmHg) were similarly reduced after 24weeks. PWV was comparable after run-in and not differently reduced by the two treatments (ENA/LER from 8.6±1.5 to 8.1±1.3m/s, p<0.05; ENA/HCT from 8.5±1.2 to 8.2±1.0m/s, p<0.05). Finally, both combinations reduced AIx, but its reduction was significantly greater (p<0.05) in ENA/LER (from 26.8±10.9 to 20.6±9.1%) than in ENA/HCT arm (from 28.2±9.0 to 24.7±8.7%). In conclusion, the combination with LER caused a similar PWV reduction as compared to HCT, but a greater reduction in AIx in hypertensive patients with metabolic syndrome not controlled by ENA alone. These results indicate a positive effect of the combination of ENA/LER on central BP augmentation, suggesting a potential additive role for cardiovascular protection.

Keywords: Arterial stiffness; Combination therapy; Enalapril maleate (PubChem CID: 5388961); Hydrochlorothiazide (PubChem CID: 3639); Hypertension; Lercanidipine (PubChem CID: 65866); Metabolic syndrome; Wave reflection.