Renin inhibitors are antihypertensive drugs that block the first step in the 
renin-angiotensin system. Their mechanism of action differs from that of the 
angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists, 
but like these drugs, renin inhibitors interrupt the negative feedback effects 
of angiotensin II on renin secretion. The renin-angiotensin-aldosterone system 
(RAAS) has long been recognized to play a significant role in hypertension 
pathophysiology. Certain agents that modify the RAAS can control blood pressure 
and improve cardiovascular outcomes. Optimization of this compound by Novartis 
led to the development of aliskiren - the only direct renin inhibitor which is 
clinically used as an antihypertensive drug. Aliskiren is the first of a new 
class of antihypertensive agents. Aliskiren is a new renin inhibitor of a novel 
structural class that has recently been shown to be efficacious in hypertensive 
patients after once-daily oral dosing. In short-term studies, it was effective 
in lowering blood pressure either alone or in combination with valsartan and 
hydrochlorothiazide, and had a low incidence of serious adverse effects. It was 
approved by the Food and Drug Administration in 2007 for the use as a 
monotherapy or in combination with other antihypertensives. Greater reductions 
in blood pressure have been achieved when aliskiren was used in combination with 
hydrochlorothiazide or an angiotensin-receptor blocker. The most common adverse 
effects reported in clinical trials were headache, fatigue, dizziness, diarrhea, 
and nasopharyngitis. Aliskiren has not been studied in patients with moderate 
renal dysfunction; as an RAAS-acting drug, it should be prescribed for such 
patients only with caution.