Long-term safety, tolerability, and antihypertensive efficacy of aliskiren, an oral direct renin inhibitor, in Japanese patients with hypertension

Inhibition of renin, the first rate-limiting enzyme in the renin-angiotensin system, has long been a therapeutic goal for treatment of hypertension. Aliskiren, the first in a new class of oral direct renin inhibitors, has been shown to reduce blood pressure (BP) in several short-term studies. In this 52-week, open-label, multicenter, parallel-group study, the long-term safety, tolerability, and efficacy of aliskiren-based therapy were assessed in Japanese patients (N=345) with mild-to-moderate essential hypertension. The study had two periods: (i) an 8-week, dose-titration period and (ii) a 44-week, fixed-dose period with an optional addition of a diuretic or a calcium channel blocker (CCB). Safety was assessed by monitoring all adverse events (AEs), serious AEs (SAEs), vital signs, laboratory parameters, ECGs, and physical examinations. Efficacy was assessed by trough mean sitting BP and responder rate. Aliskiren alone or in combination with a diuretic or a CCB was well tolerated. No deaths were reported during this study. Nine SAEs were reported, and for three of these, a possible relation to the study drug could not be excluded. The overall incidence of AEs was 85.2%, and most of these were mild-to-moderate events such as nasopharyngitis. The incidence of suspected study drug-related AEs was 25.3%. A clinically meaningful reduction of 17.6/12.8 mm Hg from baseline was achieved in the mean sitting BP at the end point with aliskiren, irrespective of the dose and additional treatments. The overall responder rate was 73.3% at the end point. In conclusion, this first long-term study in Japanese patients showed the safety and efficacy of aliskiren-based therapy in mild-to-moderate essential hypertension.