Judy W M Cheng1. 1. Massachusetts College of Pharmacy and Health Sciences and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. judy.cheng@mcphs.edu
Abstract
BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) has long been recognized to play a significant role in hypertension pathophysiology. Certain agents that modify the RAAS can control blood pressure and improve cardiovascular outcomes. Aliskiren is the first of a new class of antihypertensive agents known as renin inhibitors. OBJECTIVE: The goal of this article was to discuss the clinical pharmacology of aliskiren and its use in the management of hypertension, as well as potential uses in other cardiovascular disorders. METHODS: Peer-reviewed articles and abstracts were identified from the MEDLINE and Current Contents databases (both 1966-October 1, 2007) using the search terms aliskiren, drug interaction, pharmacokinetics, and pharmacology. Citations from available articles were reviewed for additional references. Abstracts presented at recent professional meetings were also examined. RESULTS: Nine published clinical studies have evaluated the effect of aliskiren in lowering blood pressure in hypertensive patients, either alone or in combination with other antihypertensive agents. This review summarizes those studies. Patients treated with aliskiren had significantly lower blood pressure compared with patients with mild to moderate hypertension (systolic blood pressure [SBP] 140-180 mm Hg and diastolic blood pressure [DBP] 95-110 mm Hg) who received placebo. Aliskiren in doses of 75 to 300 mg daily produced reductions of SBP (-5.3 to -15.8 mm Hg) and DBP (-5.8 to -12.3 mm Hg); placebo produced reductions of SBP that ranged from -2.85 to -10.0 mm Hg and DBP reductions from -3.26 to -8.6 mm Hg (P < 0.05 in all studies between aliskiren and placebo). Aliskiren's blood pressure-lowering effect at doses of 75 to 300 mg daily was comparable to irbesartan 150 mg daily and valsartan 80 to 360 mg daily alone. When aliskiren was added to ramipril, hydrochlorothiazide, amlodipine, irbesartan, or valsartan, significant additive blood pressure-lowering effects were reported (P < 0.05 in all clinical trials). The total incidence of adverse events was similar to placebo and other comparative agents, including irbesartan, valsartan, losartan, ramipril, and hydrochlorothiazide. The overall adverse-event rates were 22%, 35% to 52%, 25% to 52%, 34% to 55%, and 33% to 52% for aliskiren 37.5, 75, 150, 300, and 600 mg, respectively. The most commonly reported adverse events included headache, dizziness, and fatigue. Studies with cardiovascular outcomes as end points have not been performed with aliskiren. CONCLUSIONS: Aliskiren is an effective alternative agent for blood pressure management. Before aliskiren can be recommended as a routine first-line agent, however, clinical studies must explore if the blood pressure-lowering effect will translate into improvement in cardiovascular outcomes.
BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) has long been recognized to play a significant role in hypertension pathophysiology. Certain agents that modify the RAAS can control blood pressure and improve cardiovascular outcomes. Aliskiren is the first of a new class of antihypertensive agents known as renin inhibitors. OBJECTIVE: The goal of this article was to discuss the clinical pharmacology of aliskiren and its use in the management of hypertension, as well as potential uses in other cardiovascular disorders. METHODS: Peer-reviewed articles and abstracts were identified from the MEDLINE and Current Contents databases (both 1966-October 1, 2007) using the search terms aliskiren, drug interaction, pharmacokinetics, and pharmacology. Citations from available articles were reviewed for additional references. Abstracts presented at recent professional meetings were also examined. RESULTS: Nine published clinical studies have evaluated the effect of aliskiren in lowering blood pressure in hypertensivepatients, either alone or in combination with other antihypertensive agents. This review summarizes those studies. Patients treated with aliskiren had significantly lower blood pressure compared with patients with mild to moderate hypertension (systolic blood pressure [SBP] 140-180 mm Hg and diastolic blood pressure [DBP] 95-110 mm Hg) who received placebo. Aliskiren in doses of 75 to 300 mg daily produced reductions of SBP (-5.3 to -15.8 mm Hg) and DBP (-5.8 to -12.3 mm Hg); placebo produced reductions of SBP that ranged from -2.85 to -10.0 mm Hg and DBP reductions from -3.26 to -8.6 mm Hg (P < 0.05 in all studies between aliskiren and placebo). Aliskiren's blood pressure-lowering effect at doses of 75 to 300 mg daily was comparable to irbesartan 150 mg daily and valsartan 80 to 360 mg daily alone. When aliskiren was added to ramipril, hydrochlorothiazide, amlodipine, irbesartan, or valsartan, significant additive blood pressure-lowering effects were reported (P < 0.05 in all clinical trials). The total incidence of adverse events was similar to placebo and other comparative agents, including irbesartan, valsartan, losartan, ramipril, and hydrochlorothiazide. The overall adverse-event rates were 22%, 35% to 52%, 25% to 52%, 34% to 55%, and 33% to 52% for aliskiren 37.5, 75, 150, 300, and 600 mg, respectively. The most commonly reported adverse events included headache, dizziness, and fatigue. Studies with cardiovascular outcomes as end points have not been performed with aliskiren. CONCLUSIONS:Aliskiren is an effective alternative agent for blood pressure management. Before aliskiren can be recommended as a routine first-line agent, however, clinical studies must explore if the blood pressure-lowering effect will translate into improvement in cardiovascular outcomes.
Authors: Shushan B Artinian; Sawsan M Al Lafi; Suzan S Boutary; Khalil M Bitar; Nadine S Zwainy; Anwar B Bikhazi Journal: Exp Diabetes Res Date: 2011-06-04