Abstract：
UNASSIGNED: We assessed the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension.
UNASSIGNED: In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension were randomized 1:1 to receive tadalafil at a target dose of 40 mg or placebo. The primary end point was the time to the first composite event of adjudicated heart failure hospitalization or all-cause death. Secondary end points included all-cause mortality and improvements in New York Heart Association functional class or ≥10% improvement in 6-minute walking distance from baseline.
UNASSIGNED: Initially targeting 372 patients, the study was terminated early because of disruption in study medication supply. At that point, 125 patients had been randomized (placebo: 63; tadalafil: 62,). Combined primary end-point events occurred in 20 patients (32%) assigned to placebo and 17 patients (27%) assigned to tadalafil (hazard ratio, 1.02 [95% CI, 0.52-2.01]; P=0.95). There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10 [95% CI, 1.10-23.69]; P=0.04). No significant between-group differences were observed in other secondary end points. Serious adverse events occurred in 29 participants (48%) in the tadalafil group and 35 (56%) in the placebo group.
UNASSIGNED: The PASSION trial, terminated prematurely due to study medication supply disruption, does not support tadalafil use in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension, with potential safety concerns and no observed benefits in primary and secondary end points.
UNASSIGNED: URL: https://www.clinicaltrialsregister.eu/; Unique identifier: 2017-003688-37. URL: https://drks.de; Unique identifier: DRKS -DRKS00014595.
UNASSIGNED: In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension were randomized 1:1 to receive tadalafil at a target dose of 40 mg or placebo. The primary end point was the time to the first composite event of adjudicated heart failure hospitalization or all-cause death. Secondary end points included all-cause mortality and improvements in New York Heart Association functional class or ≥10% improvement in 6-minute walking distance from baseline.
UNASSIGNED: Initially targeting 372 patients, the study was terminated early because of disruption in study medication supply. At that point, 125 patients had been randomized (placebo: 63; tadalafil: 62,). Combined primary end-point events occurred in 20 patients (32%) assigned to placebo and 17 patients (27%) assigned to tadalafil (hazard ratio, 1.02 [95% CI, 0.52-2.01]; P=0.95). There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10 [95% CI, 1.10-23.69]; P=0.04). No significant between-group differences were observed in other secondary end points. Serious adverse events occurred in 29 participants (48%) in the tadalafil group and 35 (56%) in the placebo group.
UNASSIGNED: The PASSION trial, terminated prematurely due to study medication supply disruption, does not support tadalafil use in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension, with potential safety concerns and no observed benefits in primary and secondary end points.
UNASSIGNED: URL: https://www.clinicaltrialsregister.eu/; Unique identifier: 2017-003688-37. URL: https://drks.de; Unique identifier: DRKS -DRKS00014595.
摘要：
■我们评估了他达拉非的疗效和安全性，5型磷酸二酯酶抑制剂，射血分数保留的心力衰竭患者以及毛细血管后和毛细血管前肺动脉高压。
■在双盲PASSION研究（射血分数保持且合并毛细血管后和前肺动脉高压的心力衰竭患者中磷酸二酯酶-5的抑制作用）中，射血分数保留的心力衰竭患者,合并毛细血管后肺动脉高压和毛细血管前肺动脉高压的患者以1:1的比例随机分配接受他达拉非,目标剂量为40mg或安慰剂.主要终点为首次复合事件判定心力衰竭住院或全因死亡的时间。次要终点包括全因死亡率和纽约心脏协会功能等级的改善或距基线6分钟步行距离改善≥10%。
■最初针对372名患者，本研究因研究药物供应中断而提前终止.在这一点上,125名患者已被随机分配（安慰剂：63;他达拉非：62，）。合并主要终点事件发生在20例(32%)安慰剂组和17例(27%)他达拉非组(风险比,1.02[95%CI，0.52-2.01]；P=0.95）。他达拉非组可能存在全因死亡率较高的信号(风险比，5.10[95%CI，1.10-23.69]；P=0.04）。在其他次要终点没有观察到显著的组间差异。他达拉非组29例（48%）和安慰剂组35例（56%）发生严重不良事件。
■激情试验，由于研究药物供应中断而提前终止，不支持他达拉非用于射血分数保留的心力衰竭患者以及毛细血管后肺动脉高压和毛细血管前肺动脉高压，有潜在的安全性问题，并且在主要和次要终点没有观察到的益处。
■URL：https://www。临床试验登记。eu/;唯一标识符：2017-003688-37。URL：https://drks。de;唯一标识符：DRKS-DRKS00014595。
■在双盲PASSION研究（射血分数保持且合并毛细血管后和前肺动脉高压的心力衰竭患者中磷酸二酯酶-5的抑制作用）中，射血分数保留的心力衰竭患者,合并毛细血管后肺动脉高压和毛细血管前肺动脉高压的患者以1:1的比例随机分配接受他达拉非,目标剂量为40mg或安慰剂.主要终点为首次复合事件判定心力衰竭住院或全因死亡的时间。次要终点包括全因死亡率和纽约心脏协会功能等级的改善或距基线6分钟步行距离改善≥10%。
■最初针对372名患者，本研究因研究药物供应中断而提前终止.在这一点上,125名患者已被随机分配（安慰剂：63;他达拉非：62，）。合并主要终点事件发生在20例(32%)安慰剂组和17例(27%)他达拉非组(风险比,1.02[95%CI，0.52-2.01]；P=0.95）。他达拉非组可能存在全因死亡率较高的信号(风险比，5.10[95%CI，1.10-23.69]；P=0.04）。在其他次要终点没有观察到显著的组间差异。他达拉非组29例（48%）和安慰剂组35例（56%）发生严重不良事件。
■激情试验，由于研究药物供应中断而提前终止，不支持他达拉非用于射血分数保留的心力衰竭患者以及毛细血管后肺动脉高压和毛细血管前肺动脉高压，有潜在的安全性问题，并且在主要和次要终点没有观察到的益处。
■URL：https://www。临床试验登记。eu/;唯一标识符：2017-003688-37。URL：https://drks。de;唯一标识符：DRKS-DRKS00014595。
