Comparison of the Novel Angiotensin II Receptor Blocker Azilsartan Medoxomil vs Valsartan by Ambulatory Blood Pressure Monitoring

Abstract

Azilsartan medoxomil (AZL-M) is a unique angiotensin II receptor blocker (ARB) under development for the treatment of hypertension. To compare this ARB with another in the class, the authors studied the effects of AZL-M and valsartan (VAL) in 984 patients with primary hypertension in a randomized, double-blind, multicenter study using ambulatory and clinic blood pressure (BP) measurements. The primary end point was change from baseline in 24-hour mean ambulatory systolic BP following 24 weeks of treatment. Hierarchical analysis testing for noninferiority was followed by superiority testing of AZL-M (80 mg then 40 mg) vs VAL. The mean age of participants was 58 years, 52% were men, and 15% were black. Baseline 24-hour mean systolic BP was similar (approximately 145.6 mm Hg) in each group. AZL-M 40 mg and 80 mg lowered 24-hour mean systolic BP ()14.9 mm Hg and )15.3 mm Hg, respectively) more than VAL 320 mg ()11.3 mm Hg; P<.001 for 40-mg and 80-mg comparisons vs VAL). Clinic systolic BP reductions were consistent with the ambulatory results ()14.9 mm Hg for AZL-M 40 mg and )16.9 mm Hg for AZL-M 80 mg vs )11.6 mm Hg for VAL; P=.015 and P<.001, respectively). The reductions in 24-hour mean and clinic diastolic BPs were also greater with both doses of AZL-M than with VAL (P .001 for all comparisons). Small, reversible changes in serum creatinine occurred more often with AZL-M than with VAL; otherwise, safety and tolerability parameters were similar among the three groups. These data demonstrate that AZL-M across the effective dose range had superior efficacy to VAL at its maximal recommended dose without any meaningful increase in adverse events. These findings suggest that AZL-M could provide higher rates of hypertension control compared with other ARBs in the class. J Clin Hypertens (Greenwich). 2011;13:467-472. Ó2011 Wiley Periodicals, Inc.The effective lowering of blood pressure (BP) in patients with hypertension is essential to the lessening of cardiovascular events, 1,2 and various guideline-promulgating groups have advocated BP levels <140 ⁄ 90 mm Hg in patients without evidence of target-organ damage and <130 ⁄ 80 mm Hg in patients with either diabetes or heart or kidney disease. 3,4 A variety of drug classes are available for the treatment of hypertension. Head-to-head studies have shown comparable BP reduction between and within various drug classes, including angiotensin-converting enzyme inhibitors, calcium channel blockers, and angiotensin II receptor blockers (ARBs). 5,6 What typically separates these drug classes has been their sideeffect profile, with the popularity of ARBs, as such, relating to a tolerability profile similar to placebo. 7-12Azilsartan medoxomil (AZL-M) is a prodrug that is quickly hydrolyzed to the active moiety azilsartan, a potent and highly selective ARB with estimated bioavailability of 60% and elimination half-life of approximately 12 hours. 13 The major metabolite, M-II, is formed via CYP2C9 and has low affinity for the angiotensin type 1, or AT1, receptor. Based on doseranging...

Comparative study to evaluate efficacy and safety of azilsartan and telmisartan in patients with grade I-II essential hypertension

“…32,33 Azilsartan in clinically approved doses as azilsartan medoxomil has been shown to lower 24-hour BP in hypertensive patients significantly more than the maximum approved dose of olmesartan medoxomil, the later being considered by some to be one of the most potent ARBs for lowering BP. [34][35][36] Given the close structural relationship between azilsartan and candesartan, head to head studies comparing the BP effects of these two drugs are of particular interest. 37 In the present study, we have observed that both Azilsartan (40mg once daily) and Telmisartan (40mg once daily) are effective agents in reducing both systolic and diastolic BP throughout the study period when measured at the baseline with 1 st 2 nd 3 rd 4 th and 5 th week in grade I-II essential hypertension.…”

Comparative study of efficacy and adverse effects profile of azilsartan, olmesartan and candesartan in the control of essential hypertension

“…26,27 Azilsartan in clinically approved doses as azilsartan medoxomil has been shown to lower 24-hour BP in hypertensive patients significantly more than the maximum approved dose of olmesartan medoxomil, the later being considered by some to be one of the most potent ARBs for lowering BP. [28][29][30] Given the close structural relationship between azilsartan and candesartan, head to head studies comparing the BP effects of these two drugs are of particular interest. Azilsartan 40-80mg per day lowered systolic and diastolic BP significantly more than candesartan cilexetil (12mg).…”

Combination of Azilsartan Medoxomil and Chlorthalidone: Is It Possible to Fight Systemic Hypertension and Obesity Together?

“…Оба компонента доказали свою эффектив-ность в многочисленных исследованиях. Так, в иссле-довании Sica D, et al [11] было показано, что азилсар-тан в дозе 40 и 80 мг/сут. сильнее снижает суточное систолическое артериальное давление (САД) и диа-столическое артериальное давление (ДАД), чем вал-сартан в максимальной дозе 320 мг.…”