Aliskiren: an oral direct renin inhibitor for the treatment of hypertension.
Aliskiren is the first member of the new class of orally active direct renin inhibitors to receive approval from the United States Food and Drug Administration for the treatment of hypertension. In patients with hypertension, aliskiren can be used either as monotherapy or in combination with other antihypertensive agents. By inhibiting renin, aliskiren blocks the conversion of angiotensinogen to angiotensin I, which subsequently results in a reduction in angiotensin II concentrations. Unlike the angiotensin-converting enzyme inhibitors and the angiotensin II receptor blockers (ARBs), which reactively stimulate an increase in plasma renin activity, aliskiren suppresses the effects of renin and leads to a reduction in plasma renin activity. In clinical trials involving patients with mild-to-moderate hypertension, aliskiren provided antihypertensive efficacy that was comparable to that of an ARB. Combination therapy with aliskiren and an ARB may provide additional blood pressure-lowering effects compared with the respective monotherapies with each of the agents. The results from surrogate outcome studies have also alluded to the potential for aliskiren to prevent target organ damage. Because aliskiren does not significantly affect the cytochrome P450 system, it has been associated with few drug interactions. In clinical studies, aliskiren was well tolerated, and its adverse-effect profile was similar to that of placebo. Fatigue, headache, dizziness, diarrhea, nasopharyngitis, and back pain were the most commonly reported adverse events. Overall, aliskiren appears to be a reasonable treatment option for patients with mild-to-moderate hypertension who are intolerant of first-line antihypertensive therapies. Aliskiren may also be a promising renoprotective strategy in patients with concomitant hypertension and diabetes mellitus. Its potential as a first-line antihypertensive agent will have to be further examined once studies evaluating its effects on long-term clinical outcomes are completed.
Sanoski
Cynthia A
CA
Department of Pharmacy Practice, Jefferson School of Pharmacy, Jefferson College of Health Professions, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. cynthia.sanoski@jefferson.edu
D000284:Administration, Oral; D000577:Amides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D048909:Diabetes Complications / Q000188:drug therapy; D017277:Drug Approval; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005650:Fumarates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D014481:United States; D000092502:Renin Inhibitors
D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren