Comparison of valsartan 160 mg with lisinopril 20 mg, given as monotherapy or in combination with a diuretic, for the treatment of hypertension: the Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril (PREVAIL) study.

BACKGROUND

The goal of antihypertensive therapy is to provide good blood pressure (BP) control without eliciting adverse effects.

OBJECTIVE

This study compared the risk-benefit profile of the angiotensin II receptor blocker valsartan with that of the angiotensin-converting enzyme inhibitor lisinopril in patients with mild to severe hypertension. The primary objective was to show that the equipotent BP-lowering effect of the valsartan-based treatment is accompanied by a better tolerability profile.

METHODS

This 16-week, randomized, double-blind, parallel-group study was conducted at 88 outpatient centers across Italy. After a 2-week placebo run-in period, patients aged > or = 18 years with mild to severe hypertension (systolic BP [SBP], 160-220 mm Hg; diastolic BP [DBP], 95-110 mm Hg) were eligible. Patients were randomized to receive once-daily, oral, self-administered treatment with valsartan 160-mg capsules or lisinopril 20-mg capsules under double-blind conditions for 4 weeks. Responders continued monotherapy, whereas nonresponders had hydrochlorothiazide 12.5 mg added for the final 12 weeks of the study. The 2 primary variables used to assess the equivalence of therapeutic efficacy of the 2 regimens were sitting SBP and sitting DBP, which were measured at weeks 0 (baseline), 4, 8, and 16. The rate of drug-related adverse events (AEs) was used to assess whether 1 treatment had a better tolerability profile than the other. Tolerability was assessed by collecting information about AEs by means of questioning the patient or physical examination at each visit.

RESULTS

A total of 1213 patients were enrolled (635 men, 578 women; mean [SD] age, 54.5 [10.1] years [range, 28-78 years]). The study was completed by 1100 patients (553 receiving valsartan and 547 receiving lisinopril). Fifty-one patients (8.4%) treated with valsartan and 62 (10.2%) [corrected] treated with lisinopril withdrew, mainly because of AEs (9 [1.5%] and 23 patients [3.8%], respectively). The valsartan- and lisinopril-based treatments were similarly effective in reducing sitting BP, with mean SBP/DBP reductions of 31.2/15.9 mm Hg and 31.4/15.9 mm Hg, respectively. At the end of the study, BP was controlled in 82.6% [corrected] of the patients receiving valsartan and 81.6% of those receiving lisinopril. AEs were experienced by 5.1% of the patients treated with valsartan and 10.7% of those treated with lisinopril (P=.0001), with dry cough observed in 1.0% and 7.2% of patients, respectively (P<0.001).

CONCLUSIONS

Valsartan and lisinopril were both highly effective in controlling BP in these patients with mild to severe hypertension, but valsartan was associated with a significantly reduced risk for AEs, especially cough.