Aliskiren – the first of a new class of antihypertensive

Abstract

Aliskiren is the first of a new class of orally active, non-peptide, renin inhibitors. The enzyme renin is involved in the first step of the renin - angiotensin - aldosterone system (RAAS), which helps regulate blood pressure. Inhibition of renin activity suppresses the RAAS at an earlier point than that targeted by the angiotensin converting enzyme (ACE) inhibitors. Short-term, placebo-controlled studies in patients with mild-to-moderate hypertension show aliskiren monotherapy to be well tolerated and effective; it lowers blood pressure at least as effectively as the diuretic hydrochlorothiazide and the angiotensin II receptor antagonists (blockers: ARBs) irbesartan and losartan. In a 26-week study, aliskiren-based treatment had a greater antihypertensive effect than treatment based on the ACE inhibitor ramipril. Aliskiren in combination with an ACE inhibitor, an ARB, a calcium-channel blocker or with hydrochlorothiazide reduced blood pressure more effectively than the respective monotherapies in most instances. Whereas ACE inhibitors and ARBs increase plasma renin concentration and activity as a consequence of interrupting angiotensin II-mediated negative feedback on renin release, renin inhibitors decrease plasma renin activity. This is illustrated best in studies in which aliskiren neutralises the increase in plasma renin activity caused by an ACE inhibitor and an ARB. The net reduction in renin activity occurs despite the increase in plasma renin concentration that aliskiren causes. These increases are slightly larger with aliskiren than those occurring with other blockers of the renin pathway, consistent with inhibition at the rate-limiting step causing the greatest inhibition of the angiotensin II-mediated negative feedback. © 2008 CSF Medical Communications Ltd.