Effects of the Angiotensin Receptor Blocker Azilsartan Medoxomil Versus Olmesartan and Valsartan on Ambulatory and Clinic Blood Pressure in Patients With Stages 1 and 2 Hypertension
ABSTRACT Azilsartan medoxomil is an angiotensin receptor blocker (ARB) being developed for hypertension treatment. To compare this ARB with others in the class, we studied the effects of 2 doses of azilsartan medoxomil, with valsartan 320 mg and olmesartan medoxomil (olmesartan) 40 mg, in a randomized, double-blind, placebo-controlled trial using ambulatory blood pressure (BP) monitoring and clinic BP measurements. The primary efficacy end point was the change from baseline in 24-hour mean systolic BP. Hierarchical analysis testing for superiority over placebo was followed by noninferiority analysis and then superiority testing of azilsartan medoxomil (80 mg and then 40 mg) versus the comparator ARBs. For 1291 randomized patients, mean age was 56 years, 54% were men, and baseline 24-hour mean systolic BP was 145 mm Hg. Azilsartan medoxomil at 80 mg had superior efficacy to both valsartan at 320 mg and olmesartan at 40 mg: placebo-adjusted 24-hour systolic BP was lowered (-14.3 mm Hg) more than 320 mg of valsartan (-10.0 mm Hg; P<0.001) and 40 mg of olmesartan (-11.7 mm Hg; P=0.009). Azilsartan medoxomil at 40 mg was noninferior to 40 mg of olmesartan (difference: -1.4 mm Hg [95% CI: -3.3 to 0.5]). For clinic systolic BP, both doses of azilsartan medoxomil were superior to the comparator ARBs. Safety and tolerability were similar among the placebo and 4 active treatments. These data demonstrate that azilsartan medoxomil at its maximal dose has superior efficacy to both olmesartan and valsartan at their maximal, approved doses without increasing adverse events. Azilsartan medoxomil could provide higher rates of hypertension control within the ARB class.
- SourceAvailable from: George Bakris
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- "This agent is a prodrug that is hydrolyzed to azilsartan, a powerful angiotensin receptor blocker with an elimination half-life of 12 h 18. In a series of comparative studies, azilsartan medoxomil as a single agent was found to be more efficacious than other widely used angiotensin receptor blockers at their maximum approved doses 19,20. These studies included comparisons with olmesartan, which itself appears to be one of the most efficacious agents in the class 21,22. "
ABSTRACT: The aim of the study was to measure the effects on blood pressure (BP) of the angiotensin receptor blocker azilsartan medoxomil, in 40 and 80 mg doses, combined with 5 mg of the calcium channel blocker amlodipine and to compare these effects with placebo plus amlodipine 5 mg. This was a randomized, controlled, double-blind study of 6 weeks' duration in 566 patients with stage 2 hypertension. The primary endpoint was 24-h systolic BP by ambulatory monitoring. The mean age of the participants was 58 years; men and women were equally represented, and baseline 24-h BP (153-154/93 mmHg) and clinic BP (165-166/94-95 mmHg) were similar across the three treatment groups. After 6 weeks, 24-h BP decreased by 25/15 mmHg in both the azilsartan medoxomil/amlodipine 40/5 and 80/5 mg groups. These reductions were each greater than the 14/8 mmHg decrease with placebo plus amlodipine 5 mg (P≤0.001 for both comparisons). All treatments were well tolerated, and adverse events did not increase with the azilsartan medoxomil doses. Edema or fluid retention was less common in both combination groups (2.6 and 2.7%) than with placebo plus amlodipine (7.6%). Coadministration of azilsartan medoxomil with amlodipine was well tolerated and led to meaningful additional BP reductions compared with placebo plus amlodipine.Blood pressure monitoring 01/2014; 19(2). DOI:10.1097/MBP.0000000000000027 · 1.18 Impact Factor
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- "Duration Patients Intervention Primary endpoint Outcome Sica et al. 2011  24 984 patients AZM 40 mg/d (n=327) Change in 24-hour AZM 40 mg/d: -14.9 mmHg Mean age: 58 years AZM 80 mg/d (n=329) mean SBP from baseline to week 24 AZM 80 mg/d: -15.3 mmHg Female: 48% Val 320 mg/d (n=328) Val 320 mg/d: -11,3 mmHg BMI: 31 kg/m 2 (p<0.001) Race: 77% Caucasian White et al. 2011  6 1291 patients AZM 40 mg/d (n=280) Change in 24-hourmean SBP from baseline to week 24 AZM 40 mg/d: -13.4 mmHg Mean age: 56 years AZM 80 mg/d (n=285) AZM 80 mg/d: -14.5 mmHg (p=0.009 vs. OLM, p<0.001 vs. VAL) Female: 46% Valsartan 320 mg/d (n=282) BMI: 31 kg/m 2 Olmesartan 40 mg/d (n=290) Valsartan 320 mg/d: -10.2 mmHg Race: 65% Caucasian Placebo (n=154) Olmesartan 40 mg/d: -12.0 mmHg Placebo: -0.3 mmHg Bakris et al. 2011  6 1275 patients AZM 20 mg/d (n=283) AZM 20 mg/d: -12.2 mmHg Mean age: 50 years AZM 40 mg/d (n=283) AZM 40 mg/d: -13.5 mmHg Female: 50% AZM 80 mg/d (n=285) AZM 80 mg/d: -14.6 mmHg BMI: 30 kg/m 2 OLM 40 mg/d (n=282) (p=0.038 vs. OLM)) Race: 73% Caucasian Placebo (n=142) Change in 24-hour mean SBP from baseline to week 6 OLM 40 mg/d:-12.6 mmHg Placebo: -1.4 mmHg Rakugi et al. 2012  16 622 patients Azilsartan up to 40 mg/d (n=313) Change in sitting trough clinic DBP from baseline to week 16 (LOCF) Azilsartan: -12.9 mmHg Mean age: 57 years Candesartan up to 12 mg/d (n=309) Candesartan: -9.7 mmHg Female: 39% (p=0.0003) "
ABSTRACT: Arterial hypertension is highly prevalent but poorly controlled. Blood pressure (BP) reduction substantially reduces cardiovascular morbidity and mortality. Recent randomized, double-blind clinical trials demonstrated that azilsartan medoxomil (AZM) is more effective in reducing BP than the ubiquitary ACE inhibitor ramipril. Therefore, we aimed to test whether these can be verified under clinical practice conditions.Methods/design: The "Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy" (EARLY) registry is a prospective, observational, national, multicenter registry with a follow-up of up to 12 months. It will include up to 5000 patients on AZM or ACE-inhibitor monotherapy in a ratio of 7 to 3. A subgroup of patients will undergo 24-hour BP monitoring. EARLY has two co-primary objectives: 1) Description of the safety profile of azilsartan and 2) achievement of BP targets based on recent national and international guidelines for patients treated with azilsartan in comparison to those treated with ACE-inhibitors. The most important secondary endpoints are the determination of persistence with treatment and the documentation of cardiovascular and renal events. Recruitment commenced in January 2012 and will be completed by February 2013. The data obtained will supplement previous results from randomized controlled trials to document the potential value of utilizing azilsartan medoxomil in comparison to ACE-inhibitor treatment for target BP achievement in clinical practice.BMC Cardiovascular Disorders 07/2013; 13(1):46. DOI:10.1186/1471-2261-13-46 · 1.50 Impact Factor
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- "To test our hypothesis that SHRcp may have different characteristics and mechanisms of hypertension from SHR, we examined the circadian BP rhythm, the autonomic nervous system and the effect of azilsartan,13–17 a new AT1 receptor blocker (ARB), in SHRcp and compared them with SHR and Wistar‐Kyoto rats (WKY). We obtained the first evidence that SHRcp exhibit a nondipper‐type hypertension. "
ABSTRACT: This study was performed to determine the characteristics and mechanism of hypertension in SHR/NDmcr-cp(+/+) rats (SHRcp), a new model of metabolic syndrome, with a focus on the autonomic nervous system, aldosterone, and angiotensin II. We measured arterial blood pressure (BP) in SHRcp by radiotelemetry combined with spectral analysis using a fast Fourier transformation algorithm and examined the effect of azilsartan, an AT1 receptor blocker. Compared with control Wistar-Kyoto rats (WKY) and SHR, SHRcp exhibited a nondipper-type hypertension and displayed increased urinary norepinephrine excretion and increased urinary and plasma aldosterone levels. Compared with WKY and SHR, SHRcp were characterized by an increase in the low-frequency power (LF) of systolic BP and a decrease in spontaneous baroreflex gain (sBRG), indicating autonomic dysfunction. Thus, SHRcp are regarded as a useful model of human hypertension with metabolic syndrome. Oral administration of azilsartan once daily persistently lowered BP during the light period (inactive phase) and the dark period (active phase) in SHRcp more than in WKY and SHR. Thus, angiotensin II seems to be involved in the mechanism of disrupted diurnal BP rhythm in SHRcp. Azilsartan significantly reduced urinary norepinephrine and aldosterone excretion and significantly increased urinary sodium excretion in SHRcp. Furthermore, azilsartan significantly reduced LF of systolic BP and significantly increased sBRG in SHRcp. These results strongly suggest that impairment of autonomic function and increased aldosterone in SHRcp mediate the effect of angiotensin II on circadian blood pressure rhythms.Journal of the American Heart Association 04/2013; 2(3):e000035. DOI:10.1161/JAHA.113.000035 · 2.88 Impact Factor