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No benefit seen in VERITAS
Endothelins are powerful vasoconstrictive peptides that have been shown to correlate with a poor prognosis in patients with heart failure. Therefore could tezosentan, an intravenous short-acting endothelin receptor antagonist, improve outcomes in patients with acute heart failure?
Two identical, concurrent trials named VERITAS (Value of Endothelin Receptor Inhibition with Tezosentan in Acute Heart Failure Studies) were conducted over three continents and enrolled 1435 patients. All participants had been admitted within the previous 24 hours with acute decompensated heart failure that did not respond to diuretics, and went on to receive either placebo or IV tezosentan for 24–72 hours. The coprimary endpoints were change in dyspnoea (measured using a visual analogue scale at 3, 6, and 24 hours) and incidence of death or worsening heart failure at 7 days in both trials.
Baseline dyspnoea scores were similar in the two treatment groups, and the mean left ventricular ejection fraction (where measured) was 29%. The incidence of death or worsening heart failure at 7 days in the combined trials was 26% in each treatment group (p = 0.95). Similarly, no difference was seen in dyspnoea, or in secondary measures such as blood pressure and renal function. A subgroup of patients, however, did undergo right heart catheterisation and those receiving tezosentan showed improvements in pulmonary capillary wedge pressure, right atrial pressure, and pulmonary and systemic vascular resistance; furthermore, their mean cardiac index trended toward improvement compared with the control group.
The endothelin receptor antagonist bosentan has found a role in the treatment of pulmonary artery hypertension; however, as in this trial, no role has yet been found for endothelin antagonists in either acute or chronic heart failure. A phase 3 trial using tezosentan to treat right ventricular failure following cardiopulmonary bypass is ongoing.
McMurray JJV, Teerlink JR, Cotter G, . Effects of tezosentan on symptoms …
American Journal of Medicine; American Journal of Physiology: Heart and Circulatory Physiology; Annals of Emergency Medicine; Annals of Thoracic Surgery; Archives of Internal Medicine; BMJ; Chest; European Journal of Cardiothoracic Surgery; Lancet; JAMA; Journal of Clinical Investigation; Journal of Diabetes and its Complications; Journal of Immunology; Journal of Thoracic and Cardiovascular Surgery; Nature Medicine; New England Journal of Medicine; Pharmacoeconomics; Thorax
Dr Alistair C Lindsay, Dr Katie Qureshi