Pulmonary and Critical Care, Massachusetts General Hospital, Boston, Massachusetts.
Department of Pneumology, Gasthuisberg University Hospital, Leuven, Belgium.
JACC Heart Fail. 2015 Jan;3(1):1-8. doi: 10.1016/j.jchf.2014.07.013. Epub 2014 Nov 11.
This study sought to evaluate the effect of macitentan on hospitalization of patients with symptomatic pulmonary arterial hypertension (PAH).
PAH is a progressive, life-threatening disease often requiring hospitalization.
In the multicenter, double-blind, randomized, event-driven, phase III SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial, patients with symptomatic PAH were randomized (1:1:1) to receive placebo or 3 mg or 10 mg of macitentan. Effects of macitentan on the risk, rate, and number of hospital days for all-cause and PAH-related hospitalizations were compared with those for placebo. Risk and causes of hospitalizations unrelated to PAH were investigated.
Of 742 randomized patients, 250 received placebo, 250 received 3 mg of macitentan, and 242 received 10 mg of macitentan; the overall median duration of treatment was 115 weeks. Risk of all-cause hospitalization was reduced by 18.9% (p = 0.1208) and 32.3% (p = 0.0051) in the macitentan 3-mg and 10-mg arm, respectively. Rates of all-cause hospitalizations and numbers of hospital days were reduced by 20.5% (p = 0.0378) and 30.6% (p = 0.0278), respectively, with 3 mg of macitentan and by 33.1% (p = 0.0005) and 31.0% (p = 0.0336), respectively, with 10 mg of macitentan. Risk of PAH-related hospitalizations were reduced by 42.7% (p = 0.0015) and 51.6% (p < 0.0001) in the macitentan 3-mg and 10-mg arms, respectively. Rate of PAH-related hospitalizations and numbers of hospital days were reduced by 44.5% (p = 0.0004) and 53.3% (p = 0.0001), respectively, with 3 mg of macitentan, and reduced by 49.8% (p < 0.0001) and 52.3% (p = 0.0003), respectively, with 10 mg of macitentan. Risk of non-PAH-related hospitalization was similar between treatment arms.
Macitentan 10 mg significantly reduced the risk and rate of all-cause hospitalization, which was driven by reductions in the risk and rate of PAH-related hospitalization. (Study of Macitentan [ACT-064992] on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension; NCT00660179).
本研究旨在评估马西替坦对有症状的肺动脉高压（PAH）患者住院的影响。
PAH 是一种进行性、危及生命的疾病，常需住院治疗。
在多中心、双盲、随机、事件驱动、III 期 SERAPHIN（内皮素受体拮抗剂在肺动脉高压中改善临床结局的研究）试验中，有症状的 PAH 患者被随机分为（1:1:1）接受安慰剂或 3mg 或 10mg 马西替坦。与安慰剂相比，比较了马西替坦对全因和 PAH 相关住院的风险、发生率和住院天数的影响。还研究了与 PAH 无关的住院原因。
在 742 名随机患者中，250 名接受安慰剂，250 名接受 3mg 马西替坦，242 名接受 10mg 马西替坦；总的中位治疗时间为 115 周。3mg 和 10mg 马西替坦组的全因住院风险分别降低了 18.9%（p=0.1208）和 32.3%（p=0.0051）。全因住院率和住院天数分别降低了 20.5%（p=0.0378）和 30.6%（p=0.0278），3mg 马西替坦组分别降低了 33.1%（p=0.0005）和 31.0%（p=0.0336），10mg 马西替坦组分别降低了 42.7%（p=0.0015）和 51.6%（p<0.0001）。3mg 和 10mg 马西替坦组的 PAH 相关住院风险分别降低了 44.5%（p=0.0004）和 51.6%（p<0.0001）。PAH 相关住院率和住院天数分别降低了 44.5%（p=0.0004）和 53.3%（p=0.0001），3mg 马西替坦组降低了 49.8%（p<0.0001）和 52.3%（p=0.0003），10mg 马西替坦组降低了 49.8%（p<0.0001）和 52.3%（p=0.0003）。非 PAH 相关住院的风险在治疗组之间相似。
马西替坦 10mg 显著降低了全因住院的风险和发生率，这主要归因于 PAH 相关住院的风险和发生率的降低。（马西替坦在有症状的肺动脉高压患者中的发病率和死亡率研究[ACT-064992]；NCT00660179）。
