Li Xinmei, Li Te
Department of Pharmacy, Fuwai Yunnan Cardiovascular Hospital, Kunming, China.
Front Pharmacol. 2020 Apr 3;11:400. doi: 10.3389/fphar.2020.00400. eCollection 2020.
Three oral drugs (ambrisentan, bosentan, and sildenafil) have been widely used to treat patients with pulmonary arterial hypertension (PAH). 1) There are no studies that directly compare the safety and efficacy of these three drugs. Existing studies could not meet the physician's need to select the most beneficial drugs for patients. 2) Principal component analysis is mainly used for scale analysis and has not been reported in clinical field. 3) When the results of the indirect meta-analysis were not satisfactory, no new solutions have been proposed in existing meta-analysis studies.
The overall process of this study is divided into 4 steps 1) literature search and data extraction; 2) principal component analysis; 3) common reference-based indirect comparison meta-analysis; 4) formal adjusted indirect comparison.
Nine randomized controlled trials (RCTs) experiments and eight long-term experiments were selected. The main influencing factors are mortality, 6-min walk distance (6MW), mean pulmonary arterial pressure (PAP), cardiac index (CI) by principal component analysis. There was no significant heterogeneity among the indirect meta-analysis of three drugs. But in the formal adjusted indirect comparison 1) the level of PAP of sildenafil group (60.5 ± 22.35, 220) was higher than that of the other three groups, placebo (53.5 ± 17.63, 507) (p < 0.001), ambrisentan (49.5 ± 15.08, 130) (p < 0.001), and bosentan (54.6 ± 118.41, 311) (p < 0.001); 2) the level of CI of sildenafil group (54 ± 18, 311) was higher than that of the other three groups, placebo (2.7 ± 1.09, 518) (p < 0.001), ambrisentan (2.5 ± 0.75, 130) (p < 0.001), and bosentan (2.5 ± 1.06, 333) (p < 0.001). In addition, sildenafil significantly improved the survival rate comparing with ambrisentan and bosentan.
The results of this study suggest that sildenafil might be more suitable for long-term treatment of PAH patients than ambrisentan and bosentan. In order to enable clinicians to draw conclusions more quickly and directly in the data-rich literature, we suggest the use of principal component analysis combined with formal adjusted indirect comparison to compare the efficacy and safety of drugs.
三种口服药物（安立生坦、波生坦和西地那非）已被广泛用于治疗肺动脉高压（PAH）患者。1）尚无直接比较这三种药物安全性和有效性的研究。现有研究无法满足医生为患者选择最有益药物的需求。2）主成分分析主要用于量表分析，尚未在临床领域报道。3）当间接荟萃分析结果不理想时，现有荟萃分析研究未提出新的解决方案。
本研究的总体过程分为4个步骤：1）文献检索与数据提取；2）主成分分析；3）基于共同对照的间接比较荟萃分析；4）正式调整间接比较。
选择了9项随机对照试验（RCT）和8项长期试验。通过主成分分析得出的主要影响因素为死亡率、6分钟步行距离（6MW）、平均肺动脉压（PAP）、心脏指数（CI）。三种药物的间接荟萃分析中无显著异质性。但在正式调整间接比较中：1）西地那非组的PAP水平（60.5±22.35，220）高于其他三组，安慰剂组（53.5±17.63，507）（p<0.001）、安立生坦组（49.5±15.08，130）（p<0.001）和波生坦组（54.6±118.41，311）（p<0.001）；2）西地那非组的CI水平（54±18，311）高于其他三组，安慰剂组（2.7±1.09，518）（p<0.001）、安立生坦组（2.5±0.75，130）（p<0.001）和波生坦组（2.5±1.06，333）（p<0.001）。此外，与安立生坦和波生坦相比，西地那非显著提高了生存率。
本研究结果表明，与安立生坦和波生坦相比，西地那非可能更适合PAH患者的长期治疗。为了使临床医生能够在丰富的数据文献中更快、更直接地得出结论，我们建议使用主成分分析结合正式调整间接比较来比较药物的疗效和安全性。
