Stanek B, Sturm B, Frey B, Hülsmann M, Bojic A, Berger R, Rödler S, Locker G, Grimm M, Laufer G, Pacher R
Second Department of Internal Medicine, University of Vienna, Austria.
J Heart Lung Transplant. 1999 Apr;18(4):358-66. doi: 10.1016/s1053-2498(98)00064-3.
Prostaglandin E1 (PGE1) and prostacyclin have potent pulmonary and systemic vasodilating properties. This prospective, randomized trial compared PGE1 vs prostacyclin vs. low-dose dobutamine in patients with low-output heart failure awaiting heart transplantation (HTx) who were refractory to oral treatment.
Patients in advanced heart failure in New York Heart Association (NYHA) Class IV, with a cardiac index < or = 2.5 L/minute/m2 and a pulmonary capillary wedge pressure > or = 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-5m-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.
Sixty-eight patients were enrolled, 30 patients on PGE1, 8 patients on prostacyclin, and 30 patients on dobutamine. During the inpatient study phase, maximum doses were 22 +/- 1.8 ng/kg/minute for PGE1, 7 +/- 1 ng/kg/minute for prostacyclin and 5 +/- 0.4 micrograms/kg/minute for dobutamine. During the inpatient study phase 21 patients failed, 4/30 (13%) patients on PGE1, 4/8 patients on prostacyclin (50%), and 13/30 (43%) on dobutamine (p < 0.05). Long-term continuous intravenous drug infusion in outpatients was begun in 26 patients on PGE1, in 4 patients on prostacyclin, and in 17 patients on dobutamine. Infusion therapy lasted for 88 +/- 14 days in the PGE1 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 PGE1, 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.
The findings from this prospective open pilot trial suggest that continuous PGE1 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 PGE1 among other bridging agents.
前列腺素E1（PGE1）和前列环素具有强大的肺血管和全身血管舒张特性。这项前瞻性随机试验比较了PGE1、前列环素与低剂量多巴酚丁胺在等待心脏移植（HTx）且口服治疗无效的低心输出量心力衰竭患者中的疗效。
研究对象为纽约心脏协会（NYHA）IV级晚期心力衰竭患者，心脏指数≤2.5L/分钟/平方米且肺毛细血管楔压≥20mmHg，已被列入心脏移植名单。在为期12小时的住院研究阶段，治疗目标是使心输出量较基线值增加20%或更多，并使肺血管阻力降至550达因·秒/厘米⁻⁵·米⁻²以下。在长期门诊阶段，持续输注这些药物，以使用三个联合阴性终点（心力衰竭恶化、严重不良事件、死亡）分析将这些患者过渡到心脏移植。
共纳入68例患者，30例接受PGE1治疗，8例接受前列环素治疗，30例接受多巴酚丁胺治疗。在住院研究阶段，PGE1的最大剂量为22±1.8纳克/千克/分钟，前列环素为7±1纳克/千克/分钟，多巴酚丁胺为5±0.4微克/千克/分钟。在住院研究阶段，21例患者治疗失败，PGE1组4/30例（13%），前列环素组4/8例（50%），多巴酚丁胺组13/30例（43%）（p<0.05）。26例接受PGE1治疗的患者、4例接受前列环素治疗的患者和17例接受多巴酚丁胺治疗的患者开始在门诊进行长期持续静脉药物输注。PGE1组输注治疗持续88±14天，前列环素组为31±22天，多巴酚丁胺组为30±8天（无显著性差异）。在门诊阶段，23例患者达到阴性终点，16例患者心力衰竭恶化，5例发生严重不良事件，2例死亡。PGE1组26例中有7例（27%）治疗失败，前列环素组4/4例（100%）治疗失败，多巴酚丁胺组12/17例（71%）治疗失败（p<0.05，对数秩检验）。由于前列环素治疗对前8例患者无效，该试验组提前终止。
这项前瞻性开放试点试验的结果表明，与前列环素和多巴酚丁胺相比，以个体化剂量持续输注PGE1对某些患者可能是一种有用的药物过渡治疗方法，可降低心脏移植前发生心力衰竭恶化的风险。有必要进行进一步的比较研究，以探讨PGE1与其他过渡治疗药物的效果。
