Targeted Drug Combination Therapy For Pulmonary Artery Hypertension:Meta-analysis

Objective:The commonly used targeted drugs for the treatment of pulmonary artery hypertension(PAH)can be divided into three categories,including endothelin receptor antagonists(ERAs),phosphodiesterase inhibitors type 5(PDE-5i)and prostaglandin I2(PGI2).In this study,the Randomized Controlled trials(RCTS)on the combined effects of different targeted drugs on PAH were conducted,For systematically evaluating the efficacy and safety of targeted drug combination therapy for PAH.Methods:Two researchers independently searched the databases of China National Knowledge Infrastructure(CNKI),Wanfang database,Vip Chinese Science and Technology Journal Database(VIP),Cochrane library and PubMed.Retrieval of all RCTs related to combined targeted drug therapy for PAH was conducted.The time limit was from self-built database to March 2019,Language limit was Chinese and English,Literature screening and data extraction were carried out according to inclusion criteria and exclusion criteria,After cross-checking the data,two researchers used Cochrance manual to evaluate the quality of the literature and meta-analysis of the included literature using RevMan 5.3 software.Results:A total of 18 eligible literatures were included,with a total of 3273 subjects.Meta-analysis showed that the combination of targeted drugs could effectively prolong 6-Minute Walking Distance(6MWD)(WMD = 18.11,95% CI(12.40,23.81),P < 0.00001),reduce mean Pulmonary Arterial Pressure(mPAP)(WMD=-5.50,95% CI(-8.20,-2.80),P < 0.0001),pulmonary vascular resistance(PVR)(WMD=-127.41,95% CI(-177.34,-77.47),P<0.00001),WHO-FC(RR=1.19,95% CI(1.02,1.38),P=0.03)and clinical deterioration(RR=0.58,95% CI(0.47,0.71),P<0.00001),but Cardiac Output(CO)(WMD = 0.13,95% CI(-0.10,0.35),P = 0.28),Borg dyspnea index(WMD=-0.30,95% CI(-0.62,0.02),P = 0.07)and case fatality rate(RR=0.89,95%CI(0.52,1.51),P=0.66)had no significant effect,and the incidence of common adverse reactions such as headache(RR = 1.87,95% CI(1.67,2.09),P < 0.00001),flushing(RR = 2.90,95% CI(2.30,3.67),P < 0.00001)might increase.Conclusion:Compared with single use or placebo,combined use of targeted drugs can significantly improve the motor ability of PAH patients,prolong 6MWD,reduce mPAP and PVR,improve WHO-FC,and reduce the incidence of clinical deterioration.However,the effect on CO 、 Borg dyspnea index and case fatality rate are still unclear,and may also increase the occurrence of side effects such as headache and flushing.Due to the limitation of the quantity and quality of the literature,more multi-center,multi-country and high-quality RCT studies are needed to verify the above conclusions.