Effects of Combination of AT₁-Antagonist Candesartan Cilexetil and ACE-Inhibitors in Patients with Congestive Heart Failure

Abstract

Introduction Combination of ACE-inhibitors with angiotensin-II type 1 receptor antagonists could provide better blockade of RAAS system compared with monotherapy.

Objective The aim of this study was to evaluate hemodynamic and neurohumoral effects at rest and during exercise of Candesartan cilexetil as add-on therapy to ACE-inhibitors in patients with heart failure NYHA class III to IV.

Methods This was a prospective, randomized, double-blind, placebo-controlled, parallel group study. Thirty-five patients received either Candesartan 8 mg/16 mg (1st and 2nd week/ of 3-24) or placebo as add-on therapy to their previous ACE-inhibitor during a 24-weeks treatment period.

Results Peak aerobic capacity remained constant in the Candesartan group of patients (0.06±1.43 mL/min/ kg) and slightly decreased in the placebo group (-1.10±1.51 mL/min/kg), without a statistically significant difference between the groups (p=0.13). Exercise time showed a relevant increase in the Candesartan (31.9±58.5 sec) and a significant decrease in the placebo group (-25.9±85.9 sec) compared to baseline value. The difference between the studied groups was statistically significant (p<0.001). Relevant differences between the two groups were observed in the changes of right atrial pressure at rest (Candesartan: -1.9±1.7 mmHg, placebo: 1.0±2.7 mmHg, p<0.01), pulmonary capillary wedge pressure at rest (Candesartan: -3.1±3.8 mmHg, placebo: 0.2±4.6 mmHg, p<0.05) and systemic vascular resistance at maximum exercise (Candesartan: -141.9±253.3 dyne*sec/cm⁵, placebo: 47.3±221.0 dyne*sec/cm⁵, p<0.05).

Conclusion The efficacy of CHF treatment of congestive heart failure was moderately improved by Candesartan as add-on therapy to ACE-inhibitors.

Keywords: Candesartan cilexetil; angiotensin receptor blockers; ACE-inhibitors; congestive heart failure