High Blood Pressure & Cardiovascular Prevention

, Volume 18, Issue 3, pp 93–105

Direct Renin Inhibition

From Pharmacological Innovation to Novel Therapeutic Opportunities
  • Massimo Volpe
  • Roberto Pontremoli
  • Claudio Borghi
Review Article

DOI: 10.2165/11593540-000000000-00000

Cite this article as:
Volpe, M., Pontremoli, R. & Borghi, C. High Blood Press Cardiovasc Prev (2011) 18: 93. doi:10.2165/11593540-000000000-00000


Nowadays, social and economic burden related to cardiovascular and renal diseases still remains extremely high, although there has been a dramatic improvement of diagnostic options and therapeutic strategies reported in the last 30 years. The progressively higher attention towards integrated pharmacological strategies, which are able to interfere with different pathophysiological mechanisms, has certainly led to better control of cardiovascular and renal diseases. In view of the large involvement of the renin-angiotensin system (RAS) in the vast majority of pathophysiological mechanisms leading to the development and progression of cardiovascular and renal diseases, it can be easily understood why it has been long viewed as the ‘ideal’ target for the pharmacological treatment of several clinical conditions.

Recently, besides the well known therapeutic approaches for RAS blockade, based on the use of ACE inhibitors, angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) and aldosterone antagonists, both the scientific and medical community have focused their attention on a novel therapeutic option. In 2007, aliskiren, the first compound of a new drug class, the direct renin inhibitors (DRIs), has become available for clinical use, being a novel and innovative therapeutic option.

Aliskiren is able to interfere with the enzymatic activity of renin by blocking the catalytic site of the molecule and inducing an ‘upstream’ RAS blockade. This leads to a modulation of the biological properties of renin, thus resulting in the missed cleavage of angiotensinogen to angiotensin I.

Aliskiren has demonstrated antihypertensive efficacy comparable or even superior to that of other classes of antihypertensive drugs, both in monotherapy and in combination therapies. Its safety and tolerability are comparable with those of other antihypertensive drug classes and almost similar to placebo. In addition, it has been demonstrated to reduce progression of cardiac and renal organ damage in addition to ACE inhibitors or ARBs.

An ambitious and large clinical trial programme specifically designed for this innovative antihypertensive drug will evaluate the efficacy of aliskiren in terms of reduced incidence of major cardiovascular and renal outcomes in patients with hypertension and cardiovascular disease, besides the use of optimal (standard) therapeutic strategies, including ACE inhibitors and ARBs.


hypertension direct renin inhibition aliskiren ACE inhibitors angiotensin receptor blockers 

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Massimo Volpe
    • 1
    • 2
  • Roberto Pontremoli
    • 3
  • Claudio Borghi
    • 4
  1. 1.Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of MedicineUniversity of Rome “Sapienza”, Sant’Andrea HospitalRomeItaly
  2. 2.IRCCS NeuromedPozzilli, IserniaItaly
  3. 3.Division of Nephrology, Dialysis and Transplantation, San Martino HospitalUniversity of GenovaGenovaItaly
  4. 4.Division of Internal MedicineUniversity of BolognaBolognaItaly

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