Potential benefits of aliskiren beyond blood pressure reduction.

There is now clear evidence that reducing blood pressure (BP) with a broad range of agents, including angiotensin converting enzyme inhibitors and angiotensin receptor blockers, improves cardiovascular and renal outcomes. There is also evidence suggesting that these drugs have beneficial effects that are independent of BP lowering. Aliskiren is a direct renin inhibitor that interrupts the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step. Unlike angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, aliskiren produces a sustained reduction in plasma renin activity and reduces plasma levels of angiotensin II and aldosterone. Preclinical data and clinical trials in high-risk patients using surrogate markers increasingly suggest that aliskiren can reduce the progression of end-organ damage beyond that afforded by BP control. With its unique mechanism of action, combining aliskiren with another RAAS-blocking agent that has a different mechanism of action may provide more comprehensive blockade of the RAAS, potentially conferring additional clinical benefits. Evaluation of these end-organ effects in humans is underway in clinical trials designed to assess the effects of aliskiren alone and in combination with other antihypertensive agents on cardiovascular and renal outcomes.