Aliskiren, the future of renin–angiotensin system blockade?

Abstract

The suppression of the renin-angiotensin system by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been proven in many studies to treat hypertension and reduce cardiovascular events; however, reducing angiotensin I receptor stimulation results in the loss of the negative-feedback signal, leading to increased plasma renin activity. Numerous direct renin inhibitors were synthesized, but abandoned owing to low potency, poor bioavailability and short half-life. Aliskiren, a direct renin inhibitor of a novel structural class, inhibits the activity of the renin produced and, thus, its capacity to form angiotensin I, as measured by plasma renin activity. Aliskiren has been recently shown to be efficacious in hypertensive patients at once-daily oral dosing with favorable pharmacokinetics and the potential to improve end-organ protection.

An Observational, Prospective, Open-Label, Multicentre Evaluation of Aliskiren in Treated, Uncontrolled Patients

“…More recently, aliskiren, a direct renin inhibitor (DRI), which selectively antagonizes the cleavage from angiotensinogen to angiotensin I by blocking the active site of the renin enzyme, [14,15] has been evaluated in randomized controlled clinical trials on top of antihypertensive strategies in high-risk patients with hypertension. [16] Several national registries have confirmed the clinical benefits of adding aliskiren in treated hypertensive patients at high cardiovascular risk in a setting of 'real-life' practice.…”

Aliskiren: a novel renoprotective agent or simply an alternative to ACE inhibitors?

“…19 There is much speculation that it will be superior to ACEis and ARBs in preventing end-organ damage in disease states, including renal disease. 20 In this review the rationale for superior nephroprotective activity of aliskiren and the currently available evidence supporting this are discussed.…”