Effectiveness and safety of high-dose valsartan monotherapy in hypertension treatment: the ValTop study

Abstract

Early combination therapy is increasingly recommended in hypertension management because of increased risk of adverse effects with high-dose monotherapy. However, this risk is not necessarily increased for high doses of angiotensin receptor blockers (ARB). ValTop study compared efficacy and safety of high vs. conventional dose of valsartan in hypertensive patients. ValTop was a controlled, randomized, double-blind trial. Of 6035 screened subjects, 4004 mild-to-moderate hypertensive patients (mean seated diastolic blood pressure (MSDBP) 90-109 mm Hg) started 4-week open-label treatment with valsartan 160 mg. Of them, 3776 were randomized to receive valsartan 160 mg (N=1900) or 320 mg (N=1876) o.d. for 4 weeks. In 28-week open-label extension study, all participating patients (N=642) received valsartan 320 mg. Valsartan 160 mg reduced MSDBP by 10.0 mm Hg in the initial open-label phase. Further BP reductions in the double-blind phase were significantly (P<0.0001) greater in the 320 mg group than in the 160 mg group for MSDBP (1.6 ± 0.18 mm Hg vs. 0.5 ± 0.18 mm Hg) and mean seated systolic BP (3.3 ± 0.31 mm Hg vs. 0.7 ± 0.31 mm Hg). The size of the additional effect of the 320 mg dose on BP was similar in subjects controlled or not by the initial 160 mg dose. Adverse event (AE) rates were similar in both treatment groups, drug-related AEs occurring in <5% of subjects in each phase. High-dose valsartan is safe and effective in uncomplicated mild-to-moderate hypertension independently of the initial response to a moderate dose. High-dose ARB monotherapy may thus be a viable option in hypertension management.