Renin inhibition: should it supplant ACE inhibitors and ARBS in high risk patients?

Abstract

The direct renin inhibitor aliskiren has recently been approved for the treatment of hypertension in humans. The potential for these newer agents having an advantage over the existing renin-angiotensin-aldosterone system (RAAS) antagonists in the treatment of hypertension and related target organ damage has drawn the interest of several investigators. In this review, we discuss the potential advantages and disadvantages of this newest antihypertensive class over other available RAAS antagonists. The antihypertensive efficacy of aliskiren monotherapy has been compared with that of other RAAS antagonists and combinations of aliskiren with these agents. These studies have shown that aliskiren is equally effective as angiotensin receptor blockers and may be slightly more effective than angiotensin converting enzyme inhibitors in lowering blood pressure. In contrast to the other RAAS antagonists, aliskiren shuts down the entire downstream RAAS cascade. This results in greatly increased plasma renin concentration due to removal of angiotensin II-mediated feedback inhibition of renin release, which has raised concerns about whether direct renin inhibition adds anything to inhibition of downstream components of the RAAS cascade. The potential advantages and disadvantages of aliskiren therapy versus existing RAAS antagonists in treating hypertension and target organ damage are under investigation.