Renin-angiotensin-system (RAS) is an enzymatic cascade that plays a pivotal role in the development of arterial
hypertension,
kidney disease and
cardiovascular disease. Inhibition of the RAS with
angiotensin converting enzyme (
ACE) inhibitors (ACE-Is) or
angiotensin receptor blockers (ARBs) has proved to be a successful strategy for the treatment of
hypertension and related cardiovascular disorders. However, by reducing feedback inhibition of
renin release, the effects of ACE-Is and ARBs lead to an increase in plasma
renin concentration (PRC) and activity (PRA), limiting a complete inhibition of the RAS. Consequently the effects of a different pharmacological strategy that completely blocks the RAS upstream has been assessed in the last years. In this context,
aliskiren is the first representative of a new class of non-
peptide orally active
renin inhibitor that blocks the RAS at its rate-limiting step and induces a net reduction in PRA,
angiotensin II and
aldosterone levels.
Aliskiren effectively reduces blood pressure as a monotherapy as well in combination
therapy. In addition,
aliskiren has a placebo-like tolerability profile at the licensed doses of 150 mg and 300 mg.
Aliskiren also exhibits additive effects on blood pressure reduction when combined with drugs that lead to a reactive increase in the PRA, such as
diuretics, ACE-Is or ARBs. In previous studies,
aliskiren showed beneficial effects in patients with arterial
hypertension and associated clinical conditions. However, later trials indicated that the use of
aliskiren should be avoided in patients with
renal failure or receiving ACE-Is or ARBs. The main aim of this review is to summarize the available data on its efficacy and safety profile, highlighting clinical implications from recent trials.