PMID- 34060401 OWN - NLM STAT- MEDLINE DCOM- 20211117 LR - 20211117 IS - 1521-0464 (Electronic) IS - 1071-7544 (Print) IS - 1071-7544 (Linking) VI - 28 IP - 1 DP - 2021 Dec TI - Efficacy and safety of novel-targeted drugs in the treatment of pulmonary arterial hypertension: a Bayesian network meta-analysis. PG - 1007-1019 LID - 10.1080/10717544.2021.1927243 [doi] AB - Background: Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome characterized by high blood pressure and vascular remodeling in the pulmonary arterioles, which is also a rapidly progressing disease of the lung vasculature with a poor prognosis. Although PAH medication made great advances in recent years, the efficacy and safety of the medication are unsatisfactory. Therefore, we aimed to update and expand previous studies to explore the efficacy and safety of PAH-targeted medications. Methods: Relevant articles were searched and selected from published or publicly available data in PubMed, Cochrane Library, CNKI, PsycInfo, and MEDLINE (from inception until October 1(st), 2020). To assess the efficacy and safety of PAH therapies, five efficacy outcomes [6-minute walking distance (6MWD), mean pulmonary arterial pressure (mPAP), WHO functional class (WHO FC) improvement, clinical worsening, death] and two safety outcomes [adverse events (AEs), serious adverse events (SAEs)] were selected. And 6MWD was regarded as the primary efficacy outcome.Results: 50 trials included with 10 996participants were selected. In terms of efficacy, all targeted drugs were more effective than placebo. For 6MWD, Bosentan + Sildenafil, Sildenafil, Bosentan + Iloprost were better than others. Bosentan + Iloprost and Bosentan + Sildenafil were better for mPAP. Bosentan + Iloprost and Ambrisentan + Tadalafil were more effective in improving WHO FC. Bosentan + Tadalafil and Bosentan + Iloprost had the Ambrisentan probability to reduce the incidence of clinical worsening. It is demonstrated that Ambrisentan had clear benefits in reducing all-cause mortality. In terms of safety, no therapies had been shown to reduce the incidence of SAEs significantly, and Ambrisentan + Tadalafil significantly increased the incidence of AEs.Conclusions: Phosphodiesterase 5 inhibitor (PDE5i) + Endothelin Receptor Antagonists (ERA) seems to be better therapy for PAH. Prostacyclin analogs (ProsA) + ERA appear promising, though additional data is warranted.Registration PROSPERO CRD42020218818. FAU - Fu, Wenhai AU - Fu W AD - Department of Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China. FAU - He, Wenjun AU - He W AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Li, Yuexin AU - Li Y AD - Department of Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China. FAU - Chen, Yangxiao AU - Chen Y AD - Department of Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China. FAU - Liang, Jingyi AU - Liang J AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Lei, Hui AU - Lei H AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Fu, Lin AU - Fu L AD - Department of Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China. FAU - Chen, Yanghang AU - Chen Y AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Ren, Ni AU - Ren N AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Jiang, Qian AU - Jiang Q AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Shen, Yi AU - Shen Y AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Ma, Ran AU - Ma R AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Wang, Tao AU - Wang T AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Wang, Xinni AU - Wang X AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Zhang, Nuofu AU - Zhang N AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Xiao, Dakai AU - Xiao D AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. FAU - Liu, Chunli AU - Liu C AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. LA - eng PT - Journal Article PT - Meta-Analysis PL - England TA - Drug Deliv JT - Drug delivery JID - 9417471 RN - 0 (Antihypertensive Agents) RN - 0 (Vasodilator Agents) SB - IM MH - Antihypertensive Agents/*therapeutic use MH - Bayes Theorem MH - Disease Progression MH - Drug Therapy, Combination MH - Humans MH - Network Meta-Analysis MH - Pulmonary Arterial Hypertension/*drug therapy MH - Randomized Controlled Trials as Topic MH - Severity of Illness Index MH - Vasodilator Agents/*therapeutic use MH - Walk Test PMC - PMC8172220 OTO - NOTNLM OT - Pulmonary arterial hypertension OT - network meta-analysis OT - targeted drug OT - treatment COIS- All authors declare that they have no competing interests. EDAT- 2021/06/02 06:00 MHDA- 2021/11/18 06:00 PMCR- 2021/06/01 CRDT- 2021/06/01 08:41 PHST- 2021/06/01 08:41 [entrez] PHST- 2021/06/02 06:00 [pubmed] PHST- 2021/11/18 06:00 [medline] PHST- 2021/06/01 00:00 [pmc-release] AID - 1927243 [pii] AID - 10.1080/10717544.2021.1927243 [doi] PST - ppublish SO - Drug Deliv. 2021 Dec;28(1):1007-1019. doi: 10.1080/10717544.2021.1927243.