Changeover Trial of Azilsartan and Olmesartan Comparing Effects on the Renin-Angiotensin-Aldosterone System in Patients with Essential Hypertension after Cardiac Surgery (CHAOS Study)

Abstract

IntroductionEight (8) angiotensin II receptor blockers (ARBs) are currently available for clinical use internationally. Losartan was launched in Japan in 1998 and seven other ARBs have been marketed since then. Large-scale clinical studies have demonstrated various benefits of ARBs, including both antihypertensive and organ protective effects. Each of the eight ARBs also has its own unique characteristics. 1) Azilsartan was released in 2012 and is the newest ARB in Japan. Basic research comparing its antihypertensive effect with other ARBs has shown a stronger effect of azilsartan, but sufficient clinical data have not yet been obtained. 2) An in vitro study demonstrated that azilsartan had a higher affinity for the angiotensin II type 1 (AT1) receptor than other ARBs and that its dissociation from the receptor was slower. It was also reported that azilsartan demonstrates strong and persistent blocking of the actions of angiotensin II. Background: Angiotensin II receptor blockers (ARBs) have been widely used to treat hypertension and large-scale clinical studies have shown various benefits. In this study, we compared olmesartan with azilsartan, the newest ARB. Methods: The subjects were outpatients who were clinically stable after cardiac surgery. Sixty patients were randomized to receive either azilsartan or olmesartan for 1 year and were switched to the other drug for the following 1 year. The primary endpoints were the levels of plasma renin activity, angiotensin II, and aldosterone. Results: Home blood pressure exceeded 140/90 mmHg and additional antihypertensive medication was administered to 12 patients (20 episodes) in the azilsartan group versus 4 patients (4 episodes) in the olmesartan group, with the number being significantly higher in the azilsartan group. After 1 year of treatment, both angiotensin II and aldosterone levels were significantly lower in the olmesartan group than the azilsartan group. Left ventricular mass index was also significantly lower in the olmesartan group than the azilsartan group. Conclusion: This study showed that olmesartan reduces angiotensin II and aldosterone levels more effectively than azilsartan. Accordingly, it may be effective in patients with increased renin-angiotensin-aldosterone system activity after cardiac surgery or patients with severe cardiac hypertrophy.

Comparison of Efficacy and Safety of Azilsartan and Olmesartan in Patients With Essential Hypertension

“…Various doses of olmesartan (10-40 mg/day) reduced angiotensin II and aldosterone levels and left ventricular mass index more effectively than azilsartan in hypertensive outpatients who were clinically stable after cardiac surgery. 13) Thus, the results of comparisons of the beneficial effects of azilsartan and olmesartan were not consistent, and the studies included patients with different backgrounds including the doses of azilsartan and olmesartan. The depressor effect in the AZ group in the present study was not significantly different from that in the OL group and further studies will be needed to resolve this issue.…”

Stronger Effect of Azilsartan on Reduction of Proteinuria Compared to Candesartan in Patients with CKD: A Randomized Crossover Trial

“…They demonstrated that the blood pressure-lowering effects of azilsartan were noninferior to those of candesartan, and the urinary albumin-to-Cr ratio was not different between the 2 groups. Other results have varied depending on drug doses or the drugs which have been compared with azilsartan [23][24][25]. The present study demonstrated that azilsartan (20 mg) significantly reduced the percent change in proteinuria as well as systolic blood pressure compared with candesartan (8 mg).…”

Azilsartan: Current Evidence and Perspectives in Management of Hypertension

“…In the CHAOS study published by Sezai et al, the effect of azilsartan and olmesartan on plasma renin activity, aldosterone II, and angiotensin in patients with essential hypertension after cardiac surgery was studied [27]. Apart from the primary endpoint, CHAOS study also included left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), and urinalysis as secondary end point.…”