The antihypertensive effectiveness and safety of dual RAAS blockade with aliskiren and valsartan.
The renin-angiotensin-aldosterone system (RAAS) is a major factor for the development and maintenance of hypertension and a major cause for cardiovascular remodeling and cardiovascular complications through its active peptide angiotensin (Ang) II. Blockade of RAAS with ACE inhibitors (ACEIs) results in suppression of Ang II levels, which eventually return to baseline levels after prolonged ACEI administration. This leads to an escape phenomenon through generation of Ang II from enzymes other than ACE and led to the hypothesis that dual blockade of RAAS with an ACEI/Ang receptor blocker (ARB) combination could lead to total blockade of RAAS, since ARBs block the action of Ang II at the AT1 receptor level, irrespective of the mechanism of Ang II generation and will have an additive blood pressure (BP)-lowering effect. However, this hypothesis has not materialized clinically, as the ACEI/ARB combination produces modest BP reductions that are not significantly greater than monotherapy with the component drugs, and is frequently associated with higher incidence of side effects. A new dual RAAS blockade with the direct renin inhibitor aliskiren and the ARB valsartan produces greater BP reductions than monotherapy with the component drugs and is safe and well tolerated. The combination of aliskiren with valsartan, and with other antihypertensive drugs is discussed.
Chrysant
Steven G
SG
University of Oklahoma and the Oklahoma Cardiovascular and Hypertension Center, 5850 W. Eilshire Boulevard, Oklahoma City, OK 73132-4904, USA. schrysant@yahoo.com
D000577:Amides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005650:Fumarates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan; D000092502:Renin Inhibitors
D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D005650:Fumarates; D013777:Tetrazoles; D014633:Valine; D000068756:Valsartan; D000092502:Renin Inhibitors; C446481:aliskiren