Azilsartan Medoxomil for Treating Hypertension - Clinical Implications of Recent Trials

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Objective: To evaluate the efficacy, safety, and clinical role of azilsartan medoxomil, an angiotensin-II receptor blocker (ARB) that recently gained US Food and Drug Administration approval for lowering of blood pressure (BP) in patients with hypertension. Methods: A systematic review of the literature was performed through October 2011 using the keywords and medical subject headings azilsartan, azilsartan medoxomil, TAK-491, TAK-536, and Edarbi. Citations eligible for inclusion were in vitro or in vivo evaluations of azilsartan medoxomil with no restrictions on patient population or indication used. Data related to the patient populations and outcomes of interest were extracted from each citation. Results: Three trials are available in full publication form, with others available only as abstracts. Azilsartan medoxomil 40 mg and 80 mg daily significantly improves both systolic and diastolic BP from baseline compared with placebo, and the 80 mg dose has greater efficacy than other ARBs, including olmesartan 40 mg daily and valsartan 320 mg daily. Improvements in both 24-hour BP using ambulatory monitoring and clinic BPs, as well as a higher proportion of patients reaching goal, have been seen with azilsartan medoxomil. Additional information shows added BP lowering when azilsartan medoxomil is combined with chlorthalidone. Adverse events are similar with azilsartan medoxomil compared to other ARBs and include headache, dizziness, urinary tract infections, and fatigue. Conclusions: Azilsartan medoxomil is a safe and effective ARB with a unique pharmacologic profile compared with other agents, including slowed angiotensin-II type 1 (AT1) receptor dissociation rates and improved receptor specificity. Studies have shown azilsartan medoxomil 80 mg once daily to reduce BP to a greater extent than valsartan and olmesartan, with similar safety and tolerability.

Acknowledgments: Supported in part by funding from the National Institutes of Health R01 AG022092-06 (PI: Dr White).
Support: The publication costs of this article were supported by Takeda Pharmaceuticals North America. Takeda Pharmaceuticals North America has had no involvement in the content of this article beyond review for factual accuracy. William L Baker, PharmD, BCPS (AQ Cardiology), and William B White, MD, FACP, FAHA, FASH, were fully responsible for all content and editorial decisions and received no financial support or other form of compensation related to the development of the manuscript.

William L Baker, PharmD, BCPS (AQ Cardiology), has no conflicts of interest to declare. William B White, MD, FACP, FAHA, FASH, discloses that his division has received research funding from Takeda Global Research and Development, manufacturer of azilsartan medoxomil, between 2007 and 2009. He is a paid safety consultant to Takeda for chairing the adjudication committee of the febuxostat cardiovascular outcomes study. He chairs the steering committee of the Examination of cardiovascular outcomes: alogliptin versus standard of care in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE) trial assessing the cardiovascular safety of alogliptin.
William L Baker, PharmD, BCPS (AQ Cardiology), Assistant Professor of Pharmacy and Medicine, University of Connecticut Schools of Pharmacy and Medicine, 263 Farmington Avenue, MC2205, Farmington, CT 06030. E:
Received date
15 November 2011
Accepted date
20 January 2012
US Cardiology Volume 9 - Issue 1 - Spring 2012;2012:9(1):16-21
William L Baker, PharmD, BCPS (AQ Cardiology), Assistant Professor of Pharmacy and Medicine, University of Connecticut Schools of Pharmacy and Medicine, 263 Farmington Avenue, MC2205, Farmington, CT 06030. E:


Despite advances in diagnostic and treatment modalities, hypertension remains a prevalent medical condition, affecting over 26 % of the adult population, a number expected to rise to nearly 30 % by the year 2025.1 It is a major risk factor for cardiovascular disease morbidity and mortality, including stroke, heart failure, and renal disease.2,3 Numerous investigations have demonstrated the ability of various pharmacologic treatment regimens to decrease major cardiovascular event rates.4,5 Despite this evidence, adequate control of blood pressure (BP) remains poor.2,6 Pharmacologic agents that attenuate the actions of the renin–angiotensin–aldosterone system (RAAS) comprise one of the most popular antihypertensive strategies for patients with elevated BP.2,7 These include angiotensin-converting enzyme inhibitors (ACEIs), angiotensin-II receptor blockers (ARBs), direct renin inhibitors, and aldosterone antagonists. ARBs attenuate the action of angiotensin-II by binding to and inhibiting the angiotensin-II type 1 (AT1) receptor, inducing a dose-dependent decrease in peripheral resistance, reduction in vascular smooth muscle contraction, and reduced synthesis and effects of aldosterone on the kidney.8 These pharmacologic properties have led to improved outcomes with ARB use across a number of disease states, including coronary heart disease, diabetic patients with kidney disease, and heart failure.9,10
Azilsartan medoxomil (Edarbi™, Takeda Pharmaceuticals America, Inc., Deerfield, IL) is a highly selective ARB and was approved by the US Food and Drug Administration (FDA) (February 2011) for the treatment of adults with hypertension.11 Given the large number of ARBs that are currently available in the US, it is important to understand the pharmacologic and clinical characteristics of azilsartan medoxomil that may differentiate the drug for contemporary hypertension management.

Pharmacology and Pharmacokinetics

Azilsartan medoxomil is a prodrug that is hydrolyzed within the gastrointestinal tract to azilsartan prior to and/or during absorption. It is structurally related to candesartan with the exception of a chemical alteration that increases the lipophilicity of azilsartan medoxomil and potentially improves its oral bioavailability.12 Azilsartan appears to be an insurmountable selective AT1 antagonist with greater potency and a longer-lasting pharmacologic effect compared with other ARBs. Ojima et al. showed that azilsartan is more potent and has more slowly dissociating AT1 antagonist properties compared with other agents in the ARB class.13


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