Two inhaled pulmonary vasodilators worked similarly in preventing postoperative right ventricular (RV) failure after major cardiac surgery for advanced heart failure, according to a randomized study, boosting confidence for the cheaper option.
Inhaled epoprostenol (iEPO) may be deemed clinically equivalent to inhaled nitric oxide (iNO) for RV support after surgery, as the difference in postoperative RV failure rates between the two fell within the prespecified equivalence margin of 15 percentage points (25.0% vs 22.5%) in the INSPIRE-FLO trial.
Between iEPO and iNO groups, there were also no differences in the secondary outcomes of mechanical ventilation duration; hospital and intensive care unit length of stay; acute kidney injury; and mortality at 30 days, 90 days, and 1 year after orthotopic heart transplantation or left ventricular assist device (LVAD) implantation, reported researchers led by Kamrouz Ghadimi, MD, MHS, of Duke University School of Medicine in Durham, North Carolina, in .
These results add evidence that iEPO is good enough as a cost-saving option when use of the standard iNO delivery system is too expensive. Previously, a separate analysis of INSPIRE-FLO in adult lung transplantation no difference in primary graft dysfunction between iEPO and iNO.
"This is the largest and best conducted study of its kind and suggests that either inhaled pulmonary vasodilator is a reasonable choice in this study population [undergoing major cardiac surgery]. The results have cost implications as hospitals can potentially save money by choosing the lower-cost drug," commented Sean van Diepen, MD, of the University of Alberta Hospital in Edmonton.
He noted that despite the lack of high-quality evidence, iNO and iEPO have been used prophylactically and therapeutically for years to lower RV afterload and thereby lessen the RV dysfunction that is common after major cardiac surgery.
Yet whether inhaled pulmonary vasodilators should be used routinely at all is not addressed by INSPIRE-FLO, given the lack of a placebo arm. In addition, the results cannot necessarily be extrapolated to assume equal efficacy in treating patients with postoperative established RV failure, cautioned van Diepen, who was not involved with the study.
"Both of these questions are important directors for future research," he said.
The double-blind INSPIRE-FLO trial had been conducted at a single academic medical center. The present report included 231 patients randomized to continuously receive either iEPO or iNO beginning at the time of separation from cardiopulmonary bypass with the continuation of treatment into the ICU stay.
Between iEPO and iNO groups, median age was 58 and 59 years, respectively, and women comprised 29.2% and 22.5% of the cohorts. Black patients made up over 39% of both groups.
About 57% of patients underwent orthotopic heart transplantation and the rest underwent LVAD implantation.
The primary outcome was the composite RV failure rate, defined after transplantation by the initiation of mechanical circulatory support for isolated RV failure, and defined after LVAD implantation by moderate or severe right heart failure.
Ghadimi and colleagues reported that their adjusted and per-protocol analyses were consistent with the unadjusted intention-to-treat analysis that included participants who had not developed exclusions by the time of surgery.
A mortality signal suggested nonsignificant trends of higher mortality with iEPO from the in-hospital period (9.2% vs 5.4%) to 1 year (17.9% vs 9.4%). The trial's sample size may not have been large enough to detect differences in death between groups, and it is more likely that the deaths were related to various manifestations of critical illness after surgery than iEPO specifically, the investigators argued.
In any case, being a single-center study, INSPIRE-FLO may not be generalizable to all institutions.
"The results could only be applicable to heart transplant and LVAD centers and only when used as prophylactic therapy. It should be noted that not all centers used inhaled pulmonary vasodilators in all patients, and many centers may only use these drugs when there is echocardiographic, hemodynamic, or other clinical evidence of RV dysfunction or failure," van Diepen noted.
Nevertheless, "the study is a welcome and important contribution to a field of practice with a paucity of high-quality evidence," he added.
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Disclosures
The study was funded by Duke University Health System.
Ghadimi received institutional research funding from the National Institutes of Health, Duke Health, the International Anesthesia Research Society, and Octapharma.
Primary Source
Circulation
Ghadimi K, et al "Inhaled epoprostenol compared with nitric oxide for right ventricular support after major cardiac surgery" Circulation 2023; DOI: 10.1161/CIRCULATIONAHA.122.062464.