Direct inhibition of renin: a physiological approach to treat hypertension and cardiovascular disease.
Despite the last three decades of progress in improving cardiovascular outcomes via renin-angiotensin-aldosterone system (RAAS) blockade in hypertensive patients, substantial residual morbidity/mortality remains. Attempts to improve clinical outcomes by combining angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have yielded mixed results. Adverse effects of RAAS blockade with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may relate to compensatory increases in plasma renin activity (PRA). The first-in-class direct renin inhibitor, aliskiren, blocks the RAAS at its point-of-activation, suppressing PRA and attenuating increases associated with other antihypertensives. Aliskiren (with or without other agents) provides significant and prolonged blood pressure reductions in a broad range of hypertensive patients and is well tolerated. Initial results from organ-protection studies are promising. Long-term outcomes studies should yield valuable information regarding the significance of direct renin inhibition in clinical practice.
Ram
C Venkata S
CV
Texas Blood Pressure Institute, Dallas Nephrology Associates, University of Texas Southwestern, Medical Center, 1420 Viceroy Drive, Dallas, TX 75235, USA. ramv@dneph.com
D000577:Amides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000804:Angiotensin II / Q000187:drug effects; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005650:Fumarates / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000092502:Renin Inhibitors
D000577:Amides; D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren