Tezosentan (an intravenous endothelin receptor A/B antagonist) reduces peripheral resistance and increases cardiac power therefore preventing a steep decrease in blood pressure in patients with congestive heart failure

• Published in: European journal of heart failure 2001-08, Vol.3 (4), p.457-461
• Main Authors: Gad, Cotter, Wolfgang, Kiowski, Edo, Kaluski, Isaac, Kobrin, Olga, Milovanov, Alon, Marmor, Jamal, Jafari, Leonardo, Reisin, Ricardo, Krakover, Zvi, Vered, Avi, Caspi
• Format: Article
• Language: English
• Subjects: Adult; Aged; blood pressure; Blood Pressure - drug effects; Confidence Intervals; congestive heart failure; Dose-Response Relationship, Drug; Double-Blind Method; Endothelin Receptor Antagonists; Female; Follow-Up Studies; Heart Failure - complications; Heart Failure - diagnosis; Heart Failure - drug therapy; Heart Function Tests; Humans; Hypotension - prevention & control; Infusions, Intravenous; Male; Middle Aged; Probability; Pyridines - administration & dosage; Receptors, Endothelin - administration & dosage; Reference Values; Severity of Illness Index; Stroke Volume - drug effects; Tetrazoles - administration & dosage; tezosentan; Treatment Outcome; Vascular Resistance - drug effects
• ISSN: 1388-9842; 1879-0844
• DOI: 10.1016/S1388-9842(01)00168-4

Objective: This study investigated the effect of tezosentan (an intravenous endothelin-1 receptor antagonist) on vascular resistance and cardiac function and determined the dose response in patients with stable congestive heart failure (CHF) due to left ventricular systolic dysfunction. Methods: In a double-blind fashion, tezosentan or placebo were administered in ascending doses (5, 20, 50, 100 mg h−1) to 38 CHF (NYHA class III) patients with ejection fraction ≤35%, cardiac index ≤2.7 l min−1 m−2 and pulmonary capillary wedge pressure ≥ 15 mmHg. Systemic vascular resistance index (SVRi) was estimated as mean arterial blood pressure [(MAP-right atrial pressure)÷cardiac index (CI)]. Cardiac function was assessed as cardiac power index (Cpi), calculated as pressure × flow (MAP × CI), where MAP represents pressure and CI represents cardiovascular flow. Results and discussion: Compared to the placebo, tezosentan induced a dose-dependent decrease in SVRi (−32%), an increase in Cpi (+20%) and a small decrease in MAP (−9%). By contrast, patients treated with nitrate vasodilators or nesiritide (a natriuretic peptide) showed a decrease in SVRi not accompanied by a significant increase in Cpi leading to a steep decrease in MAP. Conclusions: The use of Cpi in the assessment of the hemodynamic effects of tezosentan, provides a useful alternative characterization of the complex influences of vasodilators on cardiac function in patients with CHF.