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Renin-angiotensin-aldosterone system (RAAS)

26 August 2010
Renin-angiotensin-aldosterone system (RAAS) plays an important role in development of hypertension and end-organ damage. However, optimized RAAS inhibition is difficult to achieve with current available agents because of active compensatory feedback mechanism that results in renin release and increased in plasma renin activity (PRA). In fact, elevated PRA has been associated with increase cardiovascular risk in hypertensive patients.

Direct renin inhibitor (DRI) is a new class of antihypertensive agent with the novel mechanism that directly inhibits the renin, which is the source of activation of the RAAS. It prevents the conversion of angiotensinogen to angiotensin I, thus reducing the PRA. DRI is the only known agent in the market that reduces PRA, when used as monotherapy or in combination with other agent.

DRI exhibits placebo-like tolerability, and, therefore, represents an effective and convenient antihypertensive treatment option. DRI monotherapy provides effective and dose-dependent BP lowering in hypertensive patients. Addition of DRI to any other antihypertensive classes provides significant additional blood pressure reduction compared with the respective monotherapies, without compromising the tolerability of the BP-lowering regimen.

DRI has favorable effects on vascular remodeling, on neurohumoral mediators of various forms of cardiovascular disease, including heart failure, and on proteinuria in diabetic patients. Studies of the effects of DRI on end organ damage demonstrate comparable or greater efficacy compared to other RAAS antagonists, suggesting its cardio-renal protection potential.

DRI

Starting dose

Recommended Maximum Dose

Aliskiren

150mg

300mg


Reference
Approved Malaysia Package Leaflet (Oct 2007)
Journal of the American Society of Hypertension 1(4) (2007) 264-277
Therapeutics and Clinical Risk Management 2009: 459-464


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