Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension

Abstract

In general, treatment with most angiotensin receptor blockers (ARBs) increases plasma angiotensin II (Ang II) level because of a lack of negative feedback on renin activity. Olmesartan is a potential ARB inducing activation of angiotensin-converting enzyme 2 (ACE2) that hydrolyzes Ang II to Ang 1-7, and has shown a beneficial effect on ventricular remodeling. Indeed, a previous study reported that olmesartan treatment resulted in decreased plasma levels of Ang II and aldosterone. However, there has not yet been a study showing the relationship of chronic effects of olmesartan on Ang II and the left ventricular mass index (LVMI) in comparison with those of other ARB. A total of 50 stable outpatients with essential hypertension who had received candesartan for more than 1 year were randomized into two groups: control group (n¼25): continuous candesartan treatment at a stable dose; and olmesartan group (n¼25): candesartan (8 mg day À1 ) was changed to olmesartan given at a dose of 20 mg day À1 . There was no difference in the baseline characteristics between the two groups. In the control group, there were no significant changes in blood pressure, LVMI or biomarkers during 12 months of study. In the olmesartan group, blood pressure did not change and plasma levels of Ang II decreased during 12 months of study, whereas LVMI was significantly decreased after 12 months (135 ± 36 vs. 123 ± 29 g m À2 ; Po0.01). These findings indicate that replacing candesartan with olmesartan decreased LVMI in association with a sustained decrease of plasma Ang II over a 12-month period without changing blood pressure or plasma aldosterone in patients with essential hypertension.

Do angiotensin II type 1 receptor blockers have molecular effects?

“…On the basis of those experimental studies, olmesartan and candesartan offered similar benefits for mechanical stressinduced ERKs activation, but there was a different clinical outcome in the Tsutamoto's study. 3 In contrast, there was a similar clinical outcome among ARBs, even though ARBs have different benefits on the basis of experimental studies. The presence of molecular effects for each ARB, according to experimental studies, does not necessarily reflect the clinical outcome.…”

“…25 In contrast, telmisartan was more beneficial for improving glucose and lipid profiles. 26 In conclusion, clinical trials, including that of Tsutamoto et al, 3 have shown that ARBs have different degrees of benefits. Some effects may be due to molecular effects, whereas most of the benefits conferred by ARBs are class effects.…”

“…15 This point of view is critical for the assessment of Tsutamoto's results. Tsutamoto et al 3 have observed that replacing candesartan with olmesartan decreased plasma Ang II without changing plasma aldosterone. Although they did not analyze plasma levels of Ang-(1-7), they suggested that plasma levels of Ang-(1-7) may be increased in association with the decrease in Ang II after replacement, because a previous report indicated that olmesartan increased ACE2 expression in association with an increase in plasma Ang-(1-7) after myocardial infarction in rats.…”

“…In this issue of Hypertension Research, Tsutamoto et al 3 have reported that replacing candesartan with olmesartan decreased the left ventricular mass index (LVMI) without changing blood pressure (BP) in patients with essential hypertension. This study indicated that ARBs did not all have the same effects on LVMI.…”

Effects of Olmesartan on the Renin-angiotensin-aldosterone System for Patients with Essential Hypertension after Cardiac Surgery—Investigation Using a Candesartan Change-over Study—

“…The decrease rate of LVMI was significantly higher after one year of the administration, and the decrease rates of angiotensin II and LVMI were correlated in the olmesartan group. 15) In an acute stage study of healthy individuals, olmesartan significantly lowered aldosterone, significantly increased the renin activity and showed an improvement in arterial compliance. 4) Few reports have appeared on the RAAS in relation to olmesartan, but as described previously, there have been reports on decreases in angiotensin II or aldosterone and also reports on decreases in both angiotensin II and aldosterone.…”