Article Text

Original research
Duration of dual antiplatelet therapy and stability of coronary heart disease: a 60 000-patient meta-analysis of randomised controlled trials
  1. Anda Bularga1,
  2. Mohammed N Meah1,
  3. Dimitrios Doudesis1,
  4. Anoop S V Shah2,3,
  5. Nicholas L Mills1,4,
  6. David E Newby1 and
  7. Kuan Ken Lee1
  1. 1BHF Centre for Cardiovascular Science, University of Edinburgh Division of Clinical and Surgical Sciences, Edinburgh, UK
  2. 2Department of Non-Communicable Diseases, London School of Hygiene and Tropical Medicine, London, UK
  3. 3Department of Cardiology, Imperial College Healthcare NHS Trust, London, UK
  4. 4Usher Institute, University of Edinburgh Division of Health Sciences, Edinburgh, UK
  1. Correspondence to Anda Bularga; anda.bularga{at}ed.ac.uk

Abstract

Background Dual antiplatelet therapy (DAPT) has important implications for clinical outcomes in coronary disease. However, the optimal DAPT duration remains uncertain.

Methods and results We searched four major databases for randomised controlled trials comparing long-term (≥12 months) with short-term (≤6 months) or shorter (≤3 months) DAPT in patients with coronary syndromes. The primary outcome was all-cause mortality. Secondary outcomes were any bleeding and major bleeding (safety), cardiac death, myocardial infarction, stent thrombosis, revascularisation and stroke (efficacy). Nineteen randomised controlled trials (n=60 111) satisfied inclusion criteria, 8 assessed ≤3 months DAPT. Compared with long-term (≥12 months), short-term DAPT (≤6 months) was associated with a trend towards reduced all-cause mortality (RR: 0.90, 95% CI: 0.80 to 1.01) and significant bleeding reduction (RR: 0.68, 95% CI: 0.55 to 0.83 and RR: 0.66, 95% CI: 0.56 to 0.77 for major and any bleeding, respectively). There were no significant differences in efficacy outcomes. These associations persisted in sensitivity analysis comparing shorter duration DAPT (≤3 months) to long-term DAPT (≥12 months) for all-cause mortality (RR: 0.91, 95% CI: 0.79 to 1.05). In subgroup analysis, short-term DAPT was associated with lower risk of bleeding in patients with acute or chronic coronary syndromes (RR: 0.66, 95% CI: 0.54 to 0.81 and RR: 0.53, 95% CI: 0.33 to 0.65, respectively), but higher risk of stent thrombosis in acute coronary syndrome (RR: 1.49, 95% CI: 1.02 to 2.17 vs RR: 1.25, 95% CI 0.44 to 3.58).

Conclusion Our meta-analysis suggests that short (≤6 months) and shorter (≤3 months) durations DAPT are associated with lower risk of bleeding, equivalent efficacy and a trend towards lower all-cause mortality irrespective of coronary artery disease stability.

  • acute coronary syndrome
  • angina pectoris
  • pharmacology
  • clinical

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Data tables and analysis code can be made available upon reasonable request to the corresponding author.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Data tables and analysis code can be made available upon reasonable request to the corresponding author.

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Footnotes

  • AB and MNM are joint first authors.

  • AB and MNM contributed equally.

  • Contributors AB and MNM: conceptualisation, screening, data extraction, data analysis, data interpretation, writing—original draft; DD: data analysis, writing—review and editing; ASVS and NLM: writing—review and editing; DEN: conceptualisation, writing—review and editing; KL: conceptualisation, data analysis, data interpretation, writing—review and editing.

  • Funding This work was supported by a British Heart Foundation (BHF) Research Excellence Award to the University of Edinburgh (RE/18/5/34216) and DUAL-ACS trial funding (SP/17/12/32960). AB is supported by a clinical research training fellowship (MR/V007254/1). MNM is supported by the British Heart Foundation (FS/19/46/34445). DEN and NLM are supported by the BHF through a Chair Award (CH/09/002), and Senior Clinical Research Fellowship (FS/16/14/32023), respectively. DEN is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). KL is supported by the British Heart Foundation (FS/18/25/33454).

  • Competing interests None declared.

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

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