779-1 Vasodilator Effects of the Endothelin-1 Receptor Antagonist Bosentan in Patients with Severe Chronic Heart Failure

Abstract

Patients (pts) with chronic heart failure (CHF) have increased plasma levels of the endothelial vasoconstrictor endothelin-l (ET) but it is unknown whether ET plays a role in the maintenance of vascular tone. Therefore, 24 pts with CHF NYHA III-IV were randomised in a double blind study to either Bosentan (Ro 47-0203, a potent ET-A and ET-B receptor antagonist; 100 mg followed 60 min later by 200 mg iv over 15 min each) or placebo (P1), Hemodynamics (Swan-Ganz and arterial catheters) were obtained after discontinuation of ACE-inhibitors ( > 4 plasma half lives). Pl did not result in any significant hemodynamic changes. Results for the Bosentan group are given in the table. Bos 100 mg Bas 200 mg p < Time (min) 0 20 40 60 20 40 60 MAP 84 79 77 78 76 76 75 0.001 CI 2.13 2.41 2.42 2.41 2.64 2.55 2.43 0.001 SVR 1479 1248 1224 1236 1100 1140 1182 0.001 PCWP 22.5 21.8 21.2 20.8 19.2 18.9 19.8 0.001 RA 11.1 10.0 9.5 9.5 9.3 8.6 9.1 0.001 HR 86 86 85 85 83 84 85 n.s. MAP: mean arterial pressure (mmHg), CI: cardiac index (1/min/m 2 ), SVR: systemic vascular resistance (dyn.sec.cm -5 ), PCWP: pulmonary capillary wedge pressure (mmHg), RA: right atrial pressure (mmHgl, HR: heart rate (beats/min); p values for repeated measures ANOVA. Bosentan was well tolerated and resulted in sustained systemic and venous vasodilation without reflex tachycardia and improved cardiac performance. The results, therefore, demonstrate that ET is involved in the regulation of vascular tone and that inhibition of its vascular effects may be beneficial in CHF.