Aliskiren in hypertension: evidence for its potential therapeutic value

INTRODUCTION Aliskiren is the first in a new class of antihypertensive drugs that inhibits the conversion of angiotensinogen to angiotensin I by renin, thereby inhibiting production of angiotensin II, the key mediator in the regulation of body fluid volume and blood pressure. Aliskiren is currently in phase III trials as monotherapy and phase II as combination therapy in patients with mild-to-moderate hypertension, and in phase II trials in patients with diabetic nephropathy. AIMS The aim of this review is to evaluate the emerging evidence for use of aliskiren in patients with hypertension and to predict its preliminary place in therapy in clinical outcome terms. All randomized, controlled clinical trials of aliskiren (evidence level 2) were included for analysis of efficacy with the selected outcomes of blood pressure lowering, tolerability, and adherence; all other publications were excluded. EVIDENCE REVIEW The available level 2 evidence, although limited to phase II trials, suggests that aliskiren is effective at lowering blood pressure, an accepted surrogate outcome of morbidity and mortality, in patients with mild-to-moderate uncomplicated essential hypertension. Preliminary evidence suggests aliskiren is as effective as the angiotensin receptor blocker irbesartan, but more studies are needed. The available evidence also suggests that aliskiren is well tolerated and that patients exhibit good adherence to therapy. Aliskiren's effect on outcomes such as all-cause mortality, reduction in cardiovascular mortality, and reduction in cardiovascular events in patients with mild-to-moderate essential hypertension as well as in special patient populations, remains to be determined. CLINICAL POTENTIAL The evidence available regarding aliskiren's effect on outcomes, including blood pressure, tolerability, and adherence, supports its use in patients with mild-to-moderate hypertension. Although there is some preliminary evidence from small pilot trials, the use of aliskiren in combination with other antihypertensives, and the use of aliskiren in other patient populations, cannot be recommended without further evidence.