Bridging to heart transplantation:: Prostaglandin E1 versus prostacyclin versus dobutamine

Background: Prostaglandin E(1) (PGE(1)) and prostacyclin have potent pulmonary and systemic vasodilating properties. This prospective, randomized trial compared PGE(1) vs prostacyclin vs. low-dose dobutamine in patients with low-output heart failure awaiting heart transplantation (HTx) who were refractory to oral treatment. Methods: Patients in advanced heart failure in New York Heart Association (NYHA) Class IV, with a cardiac index less than or equal to 2.5 L/minute/m(2) and a pulmonary capillary wedge pressure greater than or equal to 20 mmHg, who were listed for HTx were studied. In an inpatient study phase of 12 hours duration, therapy was aimed to increase cardiac output by 20% or more, when compared to baseline values, and to achieve a reduction of pulmonary vascular resistance below 550 dyn.s/cm(-5)m(-2). During a long-term outpatient phase, the drugs were continuously infused to bridge these patients to HTx using three combined negative endpoints (worsening heart failure, serious adverse events, death) for analysis. Results: Sixty-eight patients were enrolled, 30 patients on PGE(1), 8 patients on prostacyclin, and 30 patients on dobutamine. During the inpatient study phase, maximum doses were 22 +/- 1.8 ng/kg/minute for PGE(1), 7 +/- 1 ng/kg/minute for prostacyclin and 5 +/- 0.4 mu g/kg/minute for dobutamine. During the inpatient study phase 21 patients failed, 4/30 (13%) patients on PGE(1), 4/8 patients on prostacyclin (50%), and 13/30 (43%) an dobutamine (p < 0.05). Long-term. continuous intravenous drug infusion in outpatients was begun in 26 patients on PGE(1), in 4 patients on prostacyclin, and in 17 patients on dobutamine. Infusion therapy lasted for 88 +/- 14 days in the PGE(1) group with 31 +/- 22 days in the prostacyclin group, and 30 +/- 8 days in the dobutamine group (NS). During the outpatient phase 23 patients reached a negative endpoint with 16 patients developing worsening heart failure, 5 severe adverse events and 2 deaths. Seven out of 26 (27%) failed on PGE(1), 4/4 (100%) failed on prostacyclin, and 12/17 (71%) failed on dobutamine (p < 0.05, log rank test). Because prostacyclin treatment was ineffective in the first 8 patients, this trial arm was stopped prematurely. Conclusions: The findings from this prospective open pilot trial suggest that continuous PGE, infusions at individualized dosages can be useful in certain patients as a pharmacologic bridging procedure with reduced risk to develop worsening heart failure before HTx compared to prostacyclin and dobutamine. Further comparative studies are warranted to investigate the effects of PGE(1) among other bridging agents.