Aliskiren: the first direct renin inhibitor available for clinical use

Abstract

The idea of blocking the renin-angiotensin system (RAS) with the inhibition of the enzymatic activity of renin has been pursued for half a century, but it became a reality only recently, with the synthesis of aliskiren, the first direct renin inhibitor available for clinical use. The upstream blockade of the system induced by aliskiren, in combination with its unique pharmacological properties (inhibiting potency, high plasma concentration, long half-life and preferential partitioning in the kidney) makes this compound the ideal tool to achieve a complete blockade of the RAS. Consistent with expectations, present evidence indicates that aliskiren, at the licensed dosages of 150-300 mg/day, lowers blood pressure to the same extent as other first-line antihypertensive agents, with the additional advantage of a longer duration of action which persists for several days after the cessation of treatment. Moreover, aliskiren was found to act synergically not only with diuretics but also with other drug classes, including angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists. In addition, results of recent clinical trials have shown that aliskiren possesses cardiovascular and renal protective properties which may contribute to the beneficial effects of this drug beyond the reduction of blood pressure. Finally, aliskiren has an excellent, placebo-like tolerability profile, a feature which is very relevant for improving compliance of patients.