Source: DGNews  |  Posted 1 year ago

By Alison Palkhivala

MONTREAL -- June 29, 2010 -- Administration of an endothelin receptor blocker does not lessen rates of right ventricular failure provoked by cardiopulmonary bypass in patients with pulmonary hypertension, according to research presented here at the 2010 Annual Meeting of the Canadian Anesthesiologists' Society (CAS).

An ongoing problem with placing patients under cardiopulmonary bypass is that it can promote elevations in circulating endothelin levels, which in turn can contribute to postoperative pulmonary hypertension, right ventricular failure, and increased patient mortality. This is a particularly serious event among patients with pre-existing pulmonary hypertension.

"Whenever you have right ventricular failure after cardiac surgery, your mortality is reported to be between 44% and 86%," said André Y. Denault, MD, PhD, Department of Anesthesia, Montreal Heart Institute/Université de Montréal, Montreal, Quebec, Canada, on June 28.

"Tezosentan is a specific and potent competitive endothelin receptor antagonist with an affinity for both the A and B receptor subtypes," he said.

The study was undertaken to determine whether administration of tezosentan before and after cardiopulmonary bypass in patients with pulmonary hypertension would prevent right ventricular failure after cardiac surgery.

The study included 273 patients (in 31 centres across 14 countries) aged >=18 years who had significant documented pulmonary hypertension. The patients, who were scheduled to undergo cardiac surgery, were randomised to receive tezosentan 5 mg/hour during the surgery and 1 mg/hour after surgery up to 24 hours or a placebo.

Similar numbers of patients in each group -- 14 (10.5%) receiving tezosentan and 16 (11.3%) receiving placebo -- developed clinically relevant right ventricular failure. Similarly, no differences between the groups were seen with respect to the proportion that had a major clinical event, time to weaning from cardiopulmonary bypass, the time from the end of cardiopulmonary bypass to final discharge from intensive care. The incidence of treatment-emergent adverse events was also similar.

"The infusion of tezosentan does not reduce the incidence of clinically relevant right ventricular failure after cardiac surgery during weaning from cardiopulmonary bypass in patients with significant pulmonary hypertension," concluded Dr. Denault. "Unfortunately, a single target therapy for the prevention of right ventricular failure was not efficacious. Similar to left ventricular failure, combination strategies aimed at blocking several targets should be pursued."

Funding for this study was provided by Actelion Pharmaceuticals Ltd.

[Presentation title: Multicentered Trial of Tezosentan in Cardiac Surgery. Abstract 790429]