Is aliskiren superior to inhibitors of angiotensin-converting enzyme and angiotensin receptor blockers in renin-angiotensin system blockade?

The renin-angiotensin system (RAS) plays a crucial role in development of hypertension, heart failure, as well as in the whole process of nephropathy, particularly of diabetic nephropathy, with or without proteinuria. Blockade of RAS plays the key role in the management of hypertension and other cardiovascular diseases. Angiotensin-converting enzyme (ACE) inhibitors do not provide the full blockade of angiotensin II because it is produced through alternative pathways. Angiotensin receptor blockers (ARBs) also block the negative feedback of angiotensin II upon renin like ACE inhibitors, leading to a several fold increase in angiotensin II levels. Aliskiren is an orally-active, nonpeptidic, direct inhibitor of renin which simultaneously reduces angiotensin I, angiotensin II and plasma renin activity (PRA). This is the main point of action of aliskiren, making it completely different from ACE inhibitors and ARBs. Aliskiren introduces a new concept into the management of hypertension. However, the question concerning its real role in the management of heart failure and its place in the existing therapeutic schemes with ACE inhibitors, ARBs, beta blockers and antagonists of aldosterone receptor, will be answered by numerous ongoing studies and clinical trials. Aliskiren shows renoprotective and antiproteinuric effects similar to those of ACE inhibitors and ARBs. The available results demonstrate that aliskiren provides a new approach to the antagonism of the RAS, offering possibilities of a more efficacious and effective treatment of hypertension, heart failure and proteinuria in diabetic patient.