Zhang Huijun, Li Xiaobing, Huang Jiancheng, Li Hongying, Su Zhenyu, Wang Jun
From the Department of Cardiovascular Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, PR China.
Medicine (Baltimore). 2016 Jan;95(4):e2575. doi: 10.1097/MD.0000000000002575.
Prostacyclin analogs, such as epoprostenol, treprostinil, iloprost, and beraprost, have long been used for pulmonary arterial hypertension (PAH) treatment, yet their relative efficiency remains disputed. Eligible randomized controlled trials (RCTs) involving the 4 therapies mentioned above were retrieved from PubMed, Embase, and Cochrane (up to August 1, 2015). Odds ratios (ORs) were estimated for dichotomous data (mortality, functional class (FC) amelioration, and discontinuation); standardized mean differences (SMDs) with 95% confidence intervals (CIs) were estimated for continuous data (6-min walk distance [6-MWD]). Patients taking epoprostenol were anticipated to demonstrate more expedient 6-MWD than those taking placebo when network meta-analysis (NMA) was implemented (SMD = 52.19; 95% CI: 24.28-113.39), the trend of which was identical with that of pairwise meta-analysis (SMD = 69.28; 95% CI: 10.43-128.98). Nonetheless, the prominent advantages of treprostinil over placebo (SMD = 30.15; 95% CI: 19.29-40.01) in 6-MWD could not be replicated by NMA. Furthermore, direct and indirect (NMA) comparisons also differed in FC amelioration. For example, the superiority of epoprostenol over placebo as evident with the use of NMA (OR = 42.79; 95% CI: 10.63-301.98) could not be confirmed by pairwise meta-analysis. As suggested by indirect comparisons among 4 prostanoids, epoprostenol appears to result in remarkably favorable FC amelioration comparing to other regimens (all P < 0.05). Participants taking beraprost were more probable to withdraw in comparison with those administrated with iloprost (OR = 10.07; 95% CI: 1.47-160.65). Taking mortality, FC amelioration, discontinuation, and 6-MWD into account, epoprostenol could be recommended as an alternative treatment for patients with moderate/advanced PAH.
前列环素类似物,如依前列醇、曲前列尼尔、伊洛前列素和贝前列素,长期以来一直用于治疗肺动脉高压(PAH),但其相对疗效仍存在争议。从PubMed、Embase和Cochrane数据库(截至2015年8月1日)检索了涉及上述4种疗法的合格随机对照试验(RCT)。对二分数据(死亡率、功能分级(FC)改善和停药)估计比值比(OR);对连续数据(6分钟步行距离[6-MWD])估计标准化均数差(SMD)及其95%置信区间(CI)。进行网状Meta分析(NMA)时,预计服用依前列醇的患者6-MWD改善比服用安慰剂的患者更快(SMD = 52.19;95%CI:24.28 - 113.39),这一趋势与成对Meta分析(SMD = 69.28;95%CI:10.43 - 128.98)一致。然而,NMA无法重现曲前列尼尔在6-MWD方面相对于安慰剂的显著优势(SMD = 30.15;95%CI:19.29 - 40.01)。此外,在FC改善方面,直接比较和间接(NMA)比较也存在差异。例如,NMA显示依前列醇优于安慰剂(OR = 42.79;95%CI:10.63 - 301.98),而成对Meta分析无法证实这一点。4种前列腺素之间的间接比较表明,与其他治疗方案相比,依前列醇似乎能显著改善FC(所有P < 0.05)。与接受伊洛前列素治疗的参与者相比,服用贝前列素的参与者更有可能退出研究(OR = 10.07;95%CI:1.47 - 160.65)。综合考虑死亡率、FC改善、停药和6-MWD,依前列醇可推荐作为中度/重度PAH患者的替代治疗药物。