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De-escalation of dual antiplatelet therapy for patients with acute coronary syndrome after percutaneous coronary intervention: a systematic review and network meta-analysis
  1. Ovidio De Filippo1,2,
  2. Francesco Piroli3,
  3. Francesco Bruno1,2,
  4. Pier Paolo Bocchino1,2,
  5. Andrea Saglietto1,2,
  6. Luca Franchin4,
  7. Filippo Angelini1,2,
  8. Guglielmo Gallone1,2,
  9. Giulia Rizzello5,
  10. Mahmood Ahmad6,
  11. Mauro Gasparini5,
  12. Saurav Chatterjee7,8,
  13. Gaetano Maria De Ferrari1,2,
  14. Fabrizio D'Ascenzo1,2
  1. 1Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza Hospital, Turin, Italy
  2. 2Department of Medical Sciences, University of Turin, Turin, Italy
  3. 3S.O.C. Cardiologia Ospedaliera, Presidio Ospedaliero Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia - IRCCS, Reggio Emilia, Italy
  4. 4Cardiology Department, University Hospital 'Santa Maria della Misericordia', Azienda Sanitaria Universitaria Integrata Friuli Centrale (ASUFC), Udine, Italy
  5. 5Dipartimento di Scienze Matematiche (DISMA), Giuseppe Luigi Lagrange, Politecnico di Torino, Torino, Italy
  6. 6Royal Free London NHS Foundation Trust, London, UK
  7. 7New York Community Hospital, Maimonides Health, Brooklyn, New York, USA
  8. 8Zucker School of Medicine, Hempstead, New York, USA
  1. Correspondence to Dr Fabrizio D'Ascenzo, Cardiovascular and Thoracic Department, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino Cardiologia U, Torino, Piemonte, Italy; fabrizio.dascenzo{at}gmail.com

Abstract

Objectives To compare dual antiplatelet therapy (DAPT) de-escalation with five alternative DAPT strategies in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).

Design We conducted a systematic review and network meta-analysis (NMA). Parallel-arm randomised controlled trials (RCTs) comparing DAPT strategies were included and arms of interest were compared via NMA. Partial ranking of each identified arm and for each investigated endpoint was also performed.

Setting and participants Adult patients with ACS (≥18 years) undergoing PCI with indications for DAPT.

Search methods A comprehensive search covered several databases (PubMed, Embase, Cochrane Central, MEDLINE, Conference Proceeding Citation Index-Science) from inception to 15 October 2023. Medical subject headings and keywords related to ACS, PCI and DAPT interventions were used. Reference lists of included studies were screened. Clinical trials registers were searched for ongoing or unpublished trials.

Interventions Six strategies were assessed: T1 arm: acetylsalicylic acid (ASA) and prasugrel for 12 months; T2 arm: ASA and low-dose prasugrel for 12 months; T3 arm: ASA and ticagrelor for 12 months; T4 arm: DAPT de-escalation (ASA+P2Y12 inhibitor for 1–3 months, then single antiplatelet therapy with potent P2Y12 inhibitor or DAPT with clopidogrel); T5 arm: ASA and clopidogrel for 12 months; T6 arm: ASA and clopidogrel for 3–6 months.

Main outcome measures Primary outcome: Cardiovascular mortality. Secondary outcomes: bleeding events (all, major, minor), stent thrombosis (ST), stroke, myocardial infarction (MI), all-cause mortality, major adverse cardiovascular events (MACE).

Results 23 RCTs (75 064 patients with ACS) were included. No differences in cardiovascular mortality, all-cause death, recurrent MI or MACE were found when the six strategies were compared, although with different levels of certainty of evidence. ASA and clopidogrel for 12 or 3–6 months may result in a large increase of ST risk versus ASA plus full-dose prasugrel (OR 2.00, 95% CI 1.14 to 3.12, and OR 3.42, 95% CI 1.33 to 7.26, respectively; low certainty evidence for both comparisons). DAPT de-escalation probably results in a reduced risk of all bleedings compared with ASA plus full-dose 12-month prasugrel (OR 0.49, 95% CI 0.26 to 0.81, moderate-certainty evidence) and ASA plus 12-month ticagrelor (OR 0.52, 95% CI 0.33 to 0.75), while it may not increase the risk of ST. ASA plus 12-month clopidogrel may reduce all bleedings versus ASA plus full-dose 12-month prasugrel (OR 0.66, 95% CI 0.42 to 0.94, low certainty) and ASA plus 12-month ticagrelor (OR 0.70, 95% CI 0.52 to 0.89).

Conclusions DAPT de-escalation and ASA-clopidogrel regimens may reduce bleeding events compared with 12 months ASA and potent P2Y12 inhibitors. 3–6 months or 12-month aspirin-clopidogrel may increase ST risk compared with 12-month aspirin plus potent P2Y12 inhibitors, while DAPT de-escalation probably does not.

  • Myocardial infarction
  • Cardiology
  • Myocardial Ischemia
  • Drug-Related Side Effects and Adverse Reactions

Data availability statement

Data sharing not applicable as no data sets generated and/or analysed for this study. This systematic review and meta-analysis used aggregated, previously published data and no new data were generated. Data used for the analysis, analytical code and any other materials used for the review will not be made publicly available.

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Data availability statement

Data sharing not applicable as no data sets generated and/or analysed for this study. This systematic review and meta-analysis used aggregated, previously published data and no new data were generated. Data used for the analysis, analytical code and any other materials used for the review will not be made publicly available.

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Footnotes

  • Contributors ODF: design of the review; coordination of the review; selection of studies for inclusion in the review; collection of data for the review; assessment of the risk of bias in the included studies; assessment of the certainty in the body of evidence; interpretation of data, and; writing of the review. FP: coordination of the review; search and selection of studies for inclusion in the review; collection of data for the review; assessment of the risk of bias in the included studies; assessment of the certainty in the body of evidence; interpretation of data; writing of the review. FD’A: conception of the review; design of the review; coordination of the review; selection of studies for inclusion in the review; analysis of data; assessment of the certainty in the body of evidence; interpretation of data; writing of the review. MA: conception of the review; design of the review; coordination of the review; assessment of the risk of bias in the included studies; assessment of the certainty in the body of evidence; interpretation of data; writing of the review. AS: search and selection of studies for inclusion in the review; collection of data for the review; assessment of the risk of bias in the included studies; writing of the review. FB: search and selection of studies for inclusion in the review; collection of data for the review; assessment of the risk of bias in the included studies; writing of the review. PPB: search and selection of studies for inclusion in the review; collection of data for the review; assessment of the risk of bias in the included studies; writing of the review. LF: search and selection of studies for inclusion in the review; collection of data for the review; assessment of the risk of bias in the included studies; writing of the review. GR: analysis of the data; interpretation of the data; assessment of the certainty in the body of evidence; writing of the review. FA: search and selection of studies for inclusion in the review; collection of data for the review; assessment of the risk of bias in the included studies; writing of the review. GG: search and selection of studies for inclusion in the review; collection of data for the review; assessment of the risk of bias in the included studies; writing of the review. GMDF: coordination of the review; assessment of the certainty in the body of evidence; interpretation of data; writing of the review. MG: coordination of the review; analysis of data; assessment of the certainty in the body of evidence; interpretation of data; writing of the review. FDA is the guarantor for the full content

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.