456 ■ The Annals of Pharmacotherapy ■ 2007 March, Volume 41 www.theannals.com C ardiovascular disease is the leading cause of death in the US and world- wide. 1 Elevated blood pressure remains one of the most significant contributors to cardiovascular morbidity and mortali- ty, affecting more than 60 million people in the US and 1 billion people world- wide. By age 65, almost half of all Amer- icans have hypertension; by age 75, this value increases to 68–84%. 1,2 The Seventh Report of the Joint Na- tional Committee on prevention, detection, evaluation and treatment of high blood pressure (JNC7) recommends a blood pressure goal of less than 140/90 mm Hg in the general population, and less than 130/80 mm Hg in patients with diabetes or kidney disease. 2 Effective blood pressure control reduces the risk of stroke by 35– 40%, myocardial infarction by 20 –25%, and heart failure by 50%. JNC7 recom- mendations for initial treatment of hyper- tension include thiazide diuretics, an- giotensin-converting enzyme (ACE) in- hibitors, angiotensin receptor blockers (ARBs), β-blockers, and calcium-channel blockers. However, most hypertensive pa- tients require 2 or more medications to reach blood pressure goals. Despite the va- riety of therapeutic agents available and the clear benefits of treatment, only 59% of hypertensive patients receive treat- ment in the US, and only 34% achieve blood pressure goals. Therefore, research continues in an effort to develop new and innovative therapeutic advances that reduce blood pressure, complement existing therapy, and improve tolerability pro- files. Aliskiren is the first in a new class of antihypertensives known as renin inhibitors. Renin catalyzes the conversion of angiotensinogen to angiotensin I, the initial enzymatic reaction in the formation of angiotensin II. Previous at- tempts to develop renin inhibitors were limited by poor bioavailability, low renin specificity, and high production costs. 3 Aliskiren is a highly renin-specific, once-daily, oral- ly active agent undergoing Phase III investigation both in- ternationally and in the US for use in hypertension and other cardiovascular disorders. 3-7 A New Drug Application Aliskiren for Renin Inhibition: A New Class of Antihypertensives Benjamin W Van Tassell and Mark A Munger New Drug Developments Author information provided at the end of the text. OBJECTIVE: To review the safety, efficacy, pharmacology, pharmacokinetics, and drug interactions of aliskiren for the treatment of mild-to-moderate hypertension. DATA SOURCES: A literature search was conducted using MEDLINE (1966– January 2007), International Pharmaceutical Abstracts (1970–January 2007), and Cochrane database (2006) for the key words aliskiren or SPP100. References of selected articles were also reviewed. Abstract data were included only in the absence of significant published data. STUDY SELECTION AND DATA EXTRACTION: Available English-language data from reviews, abstracts, and clinical trials were selected. For review of efficacy, randomized controlled trials were preferred. DATA SYNTHESIS: Aliskiren is a renin inhibitor, the first in a new class of antihypertensives. As renin catalyzes the rate-limiting step of the renin– angiotensin system (RAS), renin inhibition may offer a theoretical advantage over other RAS inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). In short-term clinical trials (≤8 wk) of subjects with mild-to-moderate hypertension, single daily doses of aliskiren 150–300 mg produced significant systolic and diastolic blood pressure reduction similar to that achieved with ACE inhibitors and ARBs, with placebo-like tolerability, without an elevation in heart rate or evidence of tolerance. CONCLUSIONS: Aliskiren appears to be a safe and effective treatment option in mild-to-moderate hypertension. Although long-term outcome data have not been published, aliskiren is a promising option for RAS inhibition. KEY WORDS: aliskiren, hypertension, renin inhibitor. Ann Pharmacother 2007;41:456-64. Published Online, 6 Mar 2007, www.theannals.com, DOI 10.1345/aph.1H549 THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-07-011-H01 A For Our Patients summary of this article is available at www.ForOurPatients.info at JITRA INTL LIB on October 11, 2013 aop.sagepub.com Downloaded from at JITRA INTL LIB on October 11, 2013 aop.sagepub.com Downloaded from at JITRA INTL LIB on October 11, 2013 aop.sagepub.com Downloaded from at JITRA INTL LIB on October 11, 2013 aop.sagepub.com Downloaded from at JITRA INTL LIB on October 11, 2013 aop.sagepub.com Downloaded from at JITRA INTL LIB on October 11, 2013 aop.sagepub.com Downloaded from at JITRA INTL LIB on October 11, 2013 aop.sagepub.com Downloaded from at JITRA INTL LIB on October 11, 2013 aop.sagepub.com Downloaded from at JITRA INTL LIB on October 11, 2013 aop.sagepub.com Downloaded from