Aliskiren is the first known representative of a new class of non-peptide orally active renin inhibitors that
blocks the renin-angiotensin-aldosterone-system (RAAS) at its rate-limiting step. It induces a net reduction in plasma
renin activity (PRA), angiotensin II and aldosterone levels.
Aliskiren is effective in reducing blood pressure (BP) and is well tolerated. The incidence of adverse events and the
number of study discontinuations as a result of adverse events during aliskiren treatment were relatively low and generally
not dissimilar from placebo.
In placebo-controlled studies, aliskiren showed a dose-related systolic/diastolic BP lowering effect at doses between 75
and 300 mg/day. When compared to active treatments, aliskiren was generally as effective as hydrochlorothiazide,
angiotensin-converting-enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers, in reducing
BP. Aliskiren exhibits synergistic effects when combined with drugs that lead to a reactive increase in the PRA, such as
diuretics, ACE inhibitors or ARBs. Although in clinical studies aliskiren proved to reduce proteinuria, the early
termination of the Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (ALTITUDE)
confirms previous concerns about the full suppression of the RAAS, in this case with aliskiren combined with ACEinhibitors
or ARBs, in patients with diabetes and concomitant renal impairment.
This review summarizes the available data on its safety profile and its clinical development for treatment of arterial
hypertension, diabetes and nephropathy.