Addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure does not reduce levels of oxidative stress

Background: Angiotensin 11 exerts a number of harmful effects in patients with chronic heart failure (CHF) and, through an increase in oxidative stress, is thought to be critical in the development of endothelial dysfunction. Angiotensin II may be elevated in CHF despite treatment with angiotensin converting enzyme (ACE) inhibitors, producing a rationale for adjunctive angiotensin receptor blockade. We investigated whether the addition of angiotensin antagonism to ACE inhibition would reduce oxidative stress and improve endothelial function and exercise tolerance in patients with chronic heart failure. Methods and results: Twenty-eight heart failure patients, who were on stable ACE inhibitor therapy, were randomised to receive adjunctive therapy with candesartan or placebo. Plasma lipid-derived free radicals, TBARS and neutrophil O-2-generation, markers of oxidative stress, were measured in venous blood. Arterial endothelial function was assessed as the response of the brachial artery to flow-related shear stress. Exercise capacity was determined by cardiopulmonary exercise testing. Compared with placebo, candesartan had no effect on changes in lipid derived free radicals (-0.1 +/- 1.2 vs. -0.1 +/- 1.0 units, respectively, P=NS), TBARS (-2.2 +/- 1.1 vs. -2.6 +/- 2.2 mumol/l, respectively, P=NS) or neutrophil O-2-generating capacity (-7.3 +/- 5.1 vs. -8.4 +/- 7.9 mV/5x10(5) neutrophils, respectively, P=NS). There was no effect on changes in brachial artery flow-mediated dilatation (0.5 +/- 1.0 vs. 0.8 +/- 1.3%, respectively, P=NS) nor peak V-O2 (1.6 +/- 0.7 ml/kg per min vs. 1.8 +/- 0.6 ml/kg per min; P=NS). Conclusion: The addition of the candesartan to ACE inhibitor therapy had no effect on oxidative stress and did not improve endothelial function or exercise capacity in patients with CHE. (C) 2002 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.