A randomized, double-blind, active-controlled, parallel-group comparison of valsartan and amlodipine in the treatment of isolated systolic hypertension in elderly patients: the Val-Syst study.

BACKGROUND: Some antihypertensive therapies are limited by dose-dependent adverse effects (AEs). The angiotensin II receptor blocker valsartan has been shown to reduce blood pressure (BP) in a dose-related manner with minimal dose-limiting AEs. Amlodipine besylate is a potent dihydropyridine calcium channel blocker also with dose-related antihypertensive efficacy, but with possible dose-limiting AEs, particularly peripheral edema.

OBJECTIVES: This study compared the risk/benefit profiles of valsartan and amlodipine in elderly patients who have isolated systolic hypertension (ISH).

METHODS: This 24-week, randomized, double-blind, active-controlled, titration-to-effect, parallel-group study was conducted at 35 outpatient centers in Italy. Elderly (aged 60-80 years) patients with ISH received oral treatment with valsartan 80-mg capsules or amlodipine 5-mg capsules once daily. After 8 weeks of treatment, the dose of the patients with poorly controlled systolic BP (SBP) was titrated to 160 mg (valsartan) or 10 mg (amlodipine) once daily. At week 16, if trough SBP was still not adequately controlled, a low-dose diuretic (hydrochlorothiazide [HCTZ] 12.5 mg) was added to the treatment regimen for an additional 8 weeks. Tolerability was assessed at all study visits using physical examination and patient interview.

RESULTS: Of 421 randomized patients (231 women, 190 men; mean [SD] age, 69 [6] years), 208 were included in the valsartan group, and 213 in the amlodipine group. The efficacy of valsartan-based treatment. in reducing SBP was similar to that of amlodipine-based treatment. With doubled doses, efficacy (change in SBP) increased significantly from baseline (both P < 0.01). The frequency of AEs doubled with amlodipine 10 mg but was not clinically relevant with valsartan 160 mg. Overall, AEs were observed in 31.9% of those receiving amlodipine versus 20.2% of the patients receiving valsartan (P < 0.003), with peripheral edema rates of 26.8% and 4.8%, respectively (P < 0.001).

CONCLUSIONS: In this study population of elderly patients with ISH, valsartan-given alone or in combination with HCTZ 12.5 mg-showed similar efficacy but better tolerability than amlodipine-based treatment.