肺动脉高压靶向药物改善艾森门格综合征运动耐量及相关因素的Meta分析  

The improved exercise capacity of pulmonary arterial hypertension-specific drug therapy for Eisenmenger syndrome and related factors:A meta-analysis

作　　者：李强[1,2,3] 况虹宇 易岂建 LI Qiang;KUANG Hongyu;YI Qijian(Department of Cardiology,Children y s Hospital of Chongqing Medical University,Chongqing,400014,China;Ministry of Education Key Laboratory of Child Development and Disorders,China International Science and Technology Cooperation Base of Child development and Critical Disorders,Chongqing Key Laboratory of Pediatrics;Department of Cardiology,Chongqing Medical the Second Affiliated Hospital)

机构地区：[1]重庆医科大学附属儿童医院心内科,重庆400014 [2]儿科学重庆市重点实验室 [3]重庆市儿童发育重大疾病诊治与预防国际科技合作基地 [4]重庆医科大学附属第二医院心内科

出　　处：《临床心血管病杂志》2022年第5期403-411,共9页Journal of Clinical Cardiology

摘　　要：目的:系统评价肺动脉高压(PAH)靶向药物改善艾森门格综合征(ES)的运动耐量及相关因素分析。方法:由2名研究员对中文数据库及英文数据库进行独立检索,分别依据纳入及排除标准进行文献筛选、数据提取及质量评价。依据异质性检验结果决定采用效应模型,采用Stata 14.1统计软件进行分析,其中连续性资料采用加权均数差(WMD)及95%置信区间(CI)表示。结果:17篇文献共纳入485例ES患者,包括内皮素受体拮抗剂(ERA)研究10项,磷酸二酯酶5抑制剂(PDE5i)4项及前列环素类3项,治疗期间仅2.6%患者出现死亡,临床事件恶化率不足10%。研究结果显示靶向药物可有效改善ES患者的运动耐量,进一步分析则发现其疗效差异与靶向药物类型、ES患者人群平均年龄、药物治疗时间及是否合并唐氏综合征(DS)存在关系。ERA可提高20~30岁人群6 min步行距离(6MWD)约104.1 m(95%CI:14.12~194.08,P=0.023)及30~40岁人群6MWD约40.88 m(95%CI:17.72~64.04,P=0.001);PDE5i类药物虽可明显改善20~30岁人群的运动耐量(6MWD:WMD=+62.16 m,P<0.0001),但对30~40岁人群的运动耐量改善并不明显(6MWD:WMD=+28.00 m,P=0.656);前列环素类药物则对于30岁以上患者的6MWD改善明显(30~40岁:WMD=+307 m;>40岁:WMD=+85.75 m)。短期药物治疗(12个月以内)可明显增加纳入ES患者的6MWD约58.56 m(P<0.0001),同时改善临床心功能水平(WMD=-0.68,P<0.0001),持续靶向药物治疗则可进一步增加该类患者的运动耐量(P<0.0001)。短期口服波生坦虽不能有效提高ES合并DS患者的6MWD(WMD=+35.50 m, 95%CI:-5.89~76.88,P=0.093;I;=0.0%),但长期药物治疗后可明显改善其运动耐量(P=0.005)。结论:早期靶向药物治疗ES可明显改善患者运动耐量,同时需根据患者的临床特征选择较好的药物方案及治疗时间。Objective: To evaluate changes and related factors of exercise tolerance in pulmonary arterial hypertension(PAH)-specific drugs for Eisenmenger Syndrome(ES) systematically. Methods: Two investigators have searched Chinese databases and English databases, independently. After that, literature screening, data extraction and quality assessment were performed. The analyses used Stata 14.1 where weighted mean difference(WMD) with 95% confidence interval(CI) were calculated for the continuous data. And a randomized-effect model or a fixed-effect model was applied according to the results of the heterogeneity test. Results: Seventeen studies those met the inclusion criteria were enrolled in this review, involving485 patients with ES. It included studies about endothelin receptor antagonists(ERAs, n=10), phosophodiesterase type 5 inhibitors(PDE5 i, n=4) and prostanoids(n=3). Only 2.6% of patients died, and the rate of clinical worsening was not reach on 10%. Outcomes have showed that specific drugs could effectively improve exercise tolerance in ES patients, and it further indicated the differences might be resulted from: 1) type of the targeted drugs;2) mean age of ES patient group;3) The duration of therapeutic administration and 4) Down’s syndrome. We found that ERAs could increase 6 MWD by 104.1 meters(95%CI: 14.12-194.08, P=0.023) in groups aged 20-30 and 40.88 meters(95%CI: 17.72-64.04, P=0.001) in groups aged 30-40. Although PDE5 i drugs could significantly improve exercise capacity of individuals of a mean age at 20-30 years old level(6 MWD: WMD=+62.16 meters, P<0.0001), but not significantly improve that of ES patients at 30-40 year-old level(6 MWD: WMD=+ 28.00 meters, P=0.656). Prostacyclin drugs greatly improved 6 MWD in patients over 30 years old(30-40 years old: WMD=+307 meters;>40 years old: WMD=+85.75 meters). Short-term drug therapy(<12 months) significantly increased the 6 MWD of ES patients by 58.56 meters(P<0.0001) and improved clinical cardiac function(WMD=-0.68, P<0.0001), while continued targeted

关 键 词：肺动脉高压靶向药物 艾森门格综合征 运动耐量 相关因素 

分 类 号：R541.3[医药卫生—心血管疾病]