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Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent: systematic review and network meta-analysis

BMJ 2019; 365 doi: https://doi.org/10.1136/bmj.l2222 (Published 28 June 2019) Cite this as: BMJ 2019;365:l2222
  1. Shang-He-Lin Yin, PhD student12,
  2. Peng Xu, PhD student2,
  3. Bian Wang, PhD student2,
  4. Yao Lu, assistant researcher1,
  5. Qiao-Yu Wu, PhD student1,
  6. Meng-Li Zhou, PhD student12,
  7. Jun-Ru Wu, PhD student12,
  8. Jing-Jing Cai, professor13,
  9. Xin Sun, professor4,
  10. Hong Yuan, professor13
  1. 1Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China
  2. 2Xiangya School of Medicine, Central South University, Changsha, Hunan, China
  3. 3Department of Cardiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
  4. 4Chinese Evidence-based Medicine Centre and CREAT Group, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Centre, Chengdu, Sichuan, China
  1. Correspondence to: H Yuan yuanhong01{at}csu.edu.cn
  • Accepted 15 April 2019

Abstract

Objective To evaluate the efficacy and safety of standard term (12 months) or long term (>12 months) dual antiplatelet therapy (DAPT) versus short term (<6 months) DAPT after percutaneous coronary intervention (PCI) with drug-eluting stent (DES).

Design Systematic review and network meta-analysis.

Data sources Relevant studies published between June 1983 and April 2018 from Medline, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, ClinicalTrials.gov, and Clinicaltrialsregister.eu.

Review methods Randomised controlled trials comparing two of the three durations of DAPT (short term, standard term, and long term) after PCI with DES were included. The primary study outcomes were cardiac or non-cardiac death, all cause mortality, myocardial infarction, stent thrombosis, and all bleeding events.

Results 17 studies (n=46 864) were included. Compared with short term DAPT, network meta-analysis showed that long term DAPT resulted in higher rates of major bleeding (odds ratio 1.78, 95% confidence interval 1.27 to 2.49) and non-cardiac death (1.63, 1.03 to 2.59); standard term DAPT was associated with higher rates of any bleeding (1.39, 1.01 to 1.92). No noticeable difference was observed in other primary endpoints. The sensitivity analysis revealed that the risks of non-cardiac death and bleeding were further increased for ≥18 months of DAPT compared with short term or standard term DAPT. In the subgroup analysis, long term DAPT led to higher all cause mortality than short term DAPT in patients implanted with newer-generation DES (1.99, 1.04 to 3.81); short term DAPT presented similar efficacy and safety to standard term DAPT with acute coronary syndrome (ACS) presentation and newer-generation DES placement. The heterogeneity of pooled trials was low, providing more confidence in the interpretation of results.

Conclusions In patients with all clinical presentations, compared with short term DAPT (clopidogrel), long term DAPT led to higher rates of major bleeding and non-cardiac death, and standard term DAPT was associated with an increased risk of any bleeding. For patients with ACS, short term DAPT presented similar efficacy and safety with standard term DAPT. For patients implanted with newer-generation DES, long term DAPT resulted in more all cause mortality than short term DAPT. Although the optimal duration of DAPT should take personal ischaemic and bleeding risks into account, this study suggested short term DAPT could be considered for most patients after PCI with DES, combining evidence from both direct and indirect comparisons.

Systematic review registration PROSPERO CRD42018099519.

Footnotes

  • Contributors: JJC, XS, and HY contributed equally to this project and are joint first authors. SHLY and HY conceived and designed the project. HY and JJC supervised the project. HY, XS, and JJC performed the review and approval of the manuscript. SHLY, PX, BW, and HY contributed to the design of the study, writing the protocol, screening trials, data extraction, analysis and interpretation, and writing and final approval of the report. PX and BW contributed equally to this work. SHLY and HY generated the tables and figures. PX, SHLY, and BW assessed the quality of included trials. BW performed the literature search. SHLY, HY, and XS drafted the manuscript. SHLY, JJC, YL, QYW, MLZ, and JRW participated in revising the manuscript before submission. QYW, MLZ, and JRW contributed equally to the work. SHLY, HY, JJC, and XS participated in the formal revision, including data processing, statistical analysis, generating figures and tables, and text modification. All authors had full access to the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. HY is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: This work was supported by grants from the Major Science and Technology Project of Hunan Province (No 2016SK1001), The National Natural Science Foundation of China (No 81770403 and No 81470535) and National Key Research and Development Projects (No 2016YFC0900802). The sponsors or funders had no involvements in any parts of this study. All authors confirm the independence of researchers from funding sources.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the Major Science and Technology Project of Hunan Province, The National Natural Science Foundation of China, and National Key Research and Development Projects for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data are available.

  • The manuscript’s guarantor (HY) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned and registered have been explained.

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