经皮冠状动脉介入治疗术后应用双联抗血小板联合质子泵抑制剂安全性和有效性的荟萃分析

Objective: To analyze the impact of dual antiplatelet (DAPT) therapy combining with or without proton pump inhibitors (PPI) on the main outcomes after percutaneous coronary intervention (PCI). Methods: The PubMed, EMBASE and Cochrane Library were searched for relevant literature and the references obtained from these sources were retrieved manually from inception till September 2017. Inclusion and exclusion criteria were established follow the Cochrane review standard. A total of 977 literatures were included, 193 duplicates were excluded, 74 reviews, case reports, letters and systematic reviews were excluded, 667 literatures were excluded after reading the title and abstract, 34 literatures were excluded due to non-randomized control studies and unrelated outcome indicators, and 9 literatures were finally included with a total of 16 589 patients. RevMan 5.3 software was used to compare the incidence of major adverse cardiovascular events (MACE), cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis, stroke, gastrointestinal bleeding and gastrointestinal events in patients with DAPT combining with or without PPI after PCI. Results: MACE was observed in 8 out of the 9 included literatures, and the results showed that MACE occurred in 561 out of 6 282 patients receiving DAPT combining with PPI therapy and in 951 out of 9 632 patients using DAPT alone (OR=1.15, 95%CI 0.88-1.51, P>0.05). Cardiogenic death was observed in 7 out of the 9 included literatures, and the results showed that cardiogenic death occurred in 172 out of 6 453 patients receiving DAPT combining with PPI treatment and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Recurrent myocardial infarction was observed in 7 out of the 9 included literatures, the results showed 416 out of 6 282 cases in DAPT combining with PPI therapy group experienced recurrent myocardial infarction and 691 out of 9 632 cases in DAPT group experienced recurrent myocardial infarction (OR=1.01, 95%CI 0.89-1.16, P>0.05). Four out of 9 literatures observed revascularization. The results showed that revascularization was performed in 64 out of 2 173 patients receiving DAPT combining with PPI therapy and in 105 out of the 2 770 patients using DAPT alone (OR=1.33, 95%CI 0.55-3.24, P>0.05). All-cause death was observed in 7 out of the 9 included literatures, and the results showed that all-cause death occurred in 172 out of the 6 453 patients in DAPT combining with PPI therapy group and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Three out of the 9 included articles observed stent thrombosis, and the results showed that stent thrombosis occurred in 99 out of 2 997 patients receiving DAPT combining with PPI therapy and in 245 out of the 6 198 patients treated with DAPT (OR=1.07, 95%CI 0.83-1.37, P>0.05). Stroke was observed in 2 out of the 9 included literatures. The results showed that stroke occurred in 5 out of 2 019 patients receiving DAPT combining with PPI therapy, and in 4 out of the 2 033 patients treated with DAPT (OR=1.00, 95%CI 0.29-3.49, P>0.05). Gastrointestinal bleeding was observed in 6 out of the 9 included literatures. The results showed that gastrointestinal bleeding occurred in 26 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 93 out of the 3 506 patients treated with DAPT, gastrointestinal bleeding was significantly lower in the DAPT combining with PPI group than DAPT alone group (OR=0.27, 95%CI 0.17-0.41, P<0.01). Gastrointestinal events were reported in 6 out of the 9 included articles. Similarly, gastrointestinal events were observed in 51 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 190 out of the 3 506 patients treated with DAPT alone, the incidence of gastrointestinal events in the DAPT combined with PPI group was significantly lower than DAPT alone group (OR=0.24, 95%CI 0.14-0.42, P<0.01). Conclusions: The incidence of MACE, cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis and stroke are not affected by DAPT combined with PPI therapy after PCI, while the incidence of gastrointestinal bleeding and gastrointestinal events could be reduced by adding PPI to DAPT in patients undergoing PCI.目的： 分析经皮冠状动脉介入治疗（PCI）术后给予患者双联抗血小板（DAPT）治疗联用与不联用质子泵抑制剂（PPI）对主要结局指标的影响。 方法： 该研究为荟萃分析。计算机检索英文数据库PubMed、EMBASE、Cochrane Library，并追踪已获文献的参考文献，手工检索国际上重要会议论文集。检索时间至2017年9月。按照Cochrane系统评价要求制定纳入、排除标准。检索共获文献977篇，排除重复文献193篇，排除综述、病例报告、书信、系统评价共74篇，阅读题目和摘要后又排除文献667篇，排除非随机对照、结局指标不相关文献34篇，最终纳入文献9篇，包括患者共16 589例。运用RevMan 5.3软件比较PCI术后DAPT联用PPI和单用DAPT患者主要不良心血管事件（MACE）、心原性死亡、心肌梗死、靶血管再次血运重建、全因死亡、支架内血栓形成、卒中、消化道出血及胃肠道事件发生率。 结果： 纳入的9篇文献中有8篇观察了MACE，结果显示6 282例接受DAPT联合PPI治疗的患者中561例发生MACE，9 632例单用DAPT的患者中951例发生MACE，二者MACE发生率差异无统计学意义（OR=1.15，95%CI 0.88~1.51，P>0.05）。纳入的9篇文献中有7篇观察了心原性死亡，结果显示6 453例接受DAPT联合PPI治疗的患者中172例发生心原性死亡，9 839例单用DAPT的患者中321例发生心原性死亡，二者心原性死亡发生率差异无统计学意义（OR=0.97，95%CI 0.80~1.18，P>0.05）。纳入的9篇文献中8篇观察了再次心肌梗死，结果显示6 282例接受DAPT联合PPI治疗的患者中416例再次发生心肌梗死，9 632例单用DAPT治疗的患者中691例再次发生心肌梗死，二者心肌梗死再次发生率差异无统计学意义（OR=1.01，95%CI 0.89~1.16，P>0.05）。纳入的9篇文献中有4篇观察了血运重建，结果显示2 173例接受DAPT联合PPI治疗的患者中64例发生血运重建，2 770例单用DAPT的患者中105例发生血运重建，二者血运重建发生率差异无统计学意义（OR=1.33，95%CI 0.55~3.24，P>0.05）。纳入的9篇文献中有7篇观察了全因死亡，结果显示6 453例接受DAPT联合PPI治疗的患者中172例发生全因死亡，9 839例单用DAPT的患者中321例发生全因死亡，二者全因死亡发生率差异无统计学意义（OR=0.97，95%CI 0.80~1.18，P>0.05）。纳入的9篇文章中有3篇观察了支架内血栓形成，结果显示2 997例接受DAPT联合PPI治疗的患者中99例发生支架内血栓，6 198例单用DAPT的患者中245例发生支架内血栓，二者支架内血栓发生率差异无统计学意义（OR=1.07，95%CI 0.83~1.37，P>0.05）。纳入的9篇文献中有2篇观察了卒中，结果显示2 019例接受DAPT联合PPI治疗的患者中5例发生卒中，2 033例单用DAPT的患者中4例发生卒中，二者卒中发生率差异无统计学意义（OR=1.00，95%CI 0.29~3.49，P>0.05）。纳入的9篇文献中有6篇观察了消化道出血，结果显示3 517例接受DAPT联合PPI治疗的患者中26例发生消化道出血，3 506例单用DAPT的患者中93例发生消化道出血，前者消化道出血发生率明显低于后者（OR=0.27，95%CI 0.17~0.41，P<0.01）。纳入的9篇文章中有6篇观察了胃肠道事件，结果显示3 517例接受DAPT联合PPI治疗的患者中51例发生胃肠道事件，3 506例单用DAPT的患者中190例发生胃肠道事件，前者胃肠道事件发生率明显低于后者（OR=0.24，95%CI 0.14~0.42，P<0.01）。 结论： 冠心病PCI术后DAPT联用PPI与否不影响患者MACE、心原性死亡、再次心肌梗死、靶血管再次血运重建、全因死亡、支架内血栓形成及卒中的发生率，而联用PPI则可降低患者消化道出血及胃肠道事件的发生率。.