Effects of AT1 Receptor Antagonism With Candesartan on Endothelial Function in Patients With Hypertension and Coronary Artery Disease

Abstract

Endothelial dysfunction is a major determinant of atherosclerosis and a negative prognostic factor in patients with coronary artery disease and hypertension. Recovery of endothelial dysfunction has been associated with improved prognosis in these patients. The aim of the present study was to verify whether antagonism of angiotensin II AT1 receptors with an angiotensin receptor blocker, candesartan, improved endothelial function in patients with hypertension, stable coronary artery disease, and endothelial dysfunction. We studied 26 patients who were receiving β‐blockers with optimal blood pressure control, in a randomized, double blind study. Patients were randomized to placebo (n=13) or to candesartan 16 mg/d (n=13) for 2 months. Endothelial function was assessed by ultrasound using hyperemic flow‐mediated dilation of the brachial artery. Mean arterial blood pressure was unchanged in both groups (from 93.3±9.2 to 93.2±17.3 mm Hg in the candesartan group and from 101.3±14.2 to 102.3±13.9 mm Hg in the placebo group; both P=ns). Maximal blood flow was similar between placebo and candesartan groups at baseline and at the end of the study, whereas flow‐mediated dilation significantly increased in the candesartan group (from 5.27%±1.69% to 7.15%±2.67%; P=0.01) but remained unchanged in the placebo group (from 4.49%±1.97% to 5.88%±2.30%; P=ns). AT1 receptor antagonism with candesartan, in addition to β‐blocker therapy, improves endothelial function in high‐risk hypertensive patients.

Effect of antihypertensive therapy on endothelial markers in newly diagnosed Stage 1 hypertension: a randomized single-centre study

“…In another study that used telmisartan, an angiotensin receptor blocker, a significant increase was observed in 8-weeks FMD values versus pretreatment values in patients with SBP/DBP <180/100 mm Hg (25). Perrone-Flardi et al (26) in patients with hypertension or coronary artery disease receiving beta blockers added candesartan or placebo to the treatment; while no change was observed in the blood pressure of patients that received additional candesartan at the end of 2 months, a significant increase was observed in FMD as compared to placebo. The results of this study demonstrate that both new generation beta blockers and angiotensin receptor blockers have favourable effects on FMD.…”

Effect of Angiotensin Receptor Blockers on Flow-Mediated Vasodilation: A Meta-Analysis of Randomized Controlled Trials

“…We restricted our search spectrum to full-text articles written in English or Chinese language, and articles performed in human subjects. We identified 40 trials [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,43,44,45,46,47,48,49,50,51,52,53,54,55,56] published between 1999 and 2013. We excluded 14 trials because endothelial function was not evaluated by brachial FMD (n = 9) [43,44,45,46,47,48,49,50,51] or because FMD data were not available at baseline or at the end of treatment (n = 5; fig.…”

“…1) [52,53,54,55,56]. Among the 26 trials remaining in the present meta-analysis, 9 had a crossover design [16,17,18,22,24,27,28,32,40] and 17 had a parallel design [19,20,21,23,25,26,29,30,31,33,34,35,36,37,38,39,41]; 11 had a placebo-controlled design [17,18,19,22,24,25,27,28,31,35,38], 13 had an active drug-controlled design [16,20,21,23,26,29,30,33,34,36,39,40,41], and 2 had both of them [32,37]. In the active drug-controlled trial, the number of comparator drugs was five in 1 trial [20], four in 1 trial [37], two in 3 trials [30,36,41] and one in 10 trials [16,21,23,26,29,32,33,34,39,40].…”

“…In the active drug-controlled trial, the number of comparator drugs was five in 1 trial [20], four in 1 trial [37], two in 3 trials [30,36,41] and one in 10 trials [16,21,23,26,29,32,33,34,39,40]. The ARBs were candesartan [22,27,32,35,36] in 5 trials, irbesartan [25,26,30,31,36] in 5 trials, losartan [16,17,18,19,21,23,24,34,41] in 9 trials, olmesartan [40] in 1 trial, telmisartan [20,27,33,38] in 4 trials and valsartan [28,36,39] in 3 trials.…”

“…Several randomized controlled trials have investigated the effect of ARBs on endothelial function, which was assessed by brachial FMD in healthy subjects and patients with endothelial dysfunction caused by various diseases [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41]. In the present review, we therefore performed a meta-analysis of randomized controlled trials comparing ARBs with placebo and other classes of antihypertensive drugs in improving brachial FMD.…”