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Coronary artery disease
Original research article
Differences in relative and absolute effectiveness of oral P2Y 12 inhibition in men and women: a meta-analysis and modelling study
  1. Kuan Ken Lee1,
  2. Nicky Welton2,
  3. Anoop S Shah1,
  4. Philip D Adamson1,
  5. Sofia Dias2,
  6. Atul Anand1,
  7. David E Newby1,
  8. Nicholas L Mills1,
  9. David A McAllister3
  1. 1 BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
  2. 2 School of Social and Community Medicine, University of Bristol, Bristol, UK
  3. 3 Institute for Health and Wellbeing, University of Glasgow, Glasgow, UK
  1. Correspondence to Dr David A McAllister, Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8RZ, UK; david.mcallister{at}glasgow.ac.uk

Abstract

Objective To estimate the absolute treatment effects of newer P2Y12 inhibitors (ticagrelor and prasugrel) compared with clopidogrel in men and women with acute coronary syndrome (ACS).

Methods We searched Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials of oral P2Y12 inhibitors for acute stroke or ACS. Age-specific and sex-specific mortality was obtained for all patients admitted to hospital with myocardial infarction in Scotland from 2006 to 2010 (prior to introduction of prasugrel or ticagrelor).

Results From 9277 articles, nine fulfilled our inclusion criteria. Three trials compared newer P2Y12 inhibitors to clopidogrel in ACS, in which the treatment rate ratio (RR) for major adverse cardiovascular events in men was 0.80 (95% CI 0.69 to 0.93). For the same outcome, across all nine trials, the sex–treatment interaction RR was 1.08 (95% CI 0.98 to 1.19). Combining these estimates yielded a treatment RR in women of 0.86 (95% CI 0.72 to 1.04).

17 842 women and 27 818 men were admitted to hospital with myocardial infarction. Mortality was higher for women than men for all-cause (5708, 32.0% vs 5891, 21.2%), cardiovascular (4032, 22.6% vs 4117, 14.8%) and bleeding (193, 1.1% vs 228, 0.8%) deaths.

On applying the sex-specific RRs to this population, the absolute risk reduction for mortality at 1 year was similar for women and men for all-cause (2.30% (95% CI −0.92% to 5.22%) vs 2.47% (95% CI 0.62% to 4.10%)), cardiovascular (2.70% (95% CI −0.63% to 5.74%)) vs 2.72% (95% CI 0.92% to 4.35%)) and bleeding (−0.27% (95% CI −1.06% to 0.30%) vs −0.18% (95% CI −0.71% to 0.24%)) deaths.

Conclusion Newer P2Y12 inhibitors may be slightly less efficacious in women than men, but the absolute risk reduction is similar in both sexes.

  • acute coronary syndromes
  • acute myocardial infarction
  • epidemiology and meta-analysis

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/heartjnl-2017-312003

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    Footnotes

    • Contributors KKL, AS, NLM and DM conceived and designed the study. DM conducted the statistical analysis and interpreted the results. SD and NW advised on the design and conduct of the statistical analysis and the interpretation of the results. KKL, AS and PDA conducted the systematic review. KKL and DM initially drafted the manuscript. All authors interpreted the findings, made critical revisions of the manuscript for intellectual content and had final approval of the version published.

    • Funding This work was supported by the Wellcome Trust (201492-Z-16-Z and WT103782AIA) and British Heart Foundation (FS/16/14/32023 and CH/09/002).

    • Competing interests AA and AS have received honoraria from Abbott Diagnostics. NLM has acted as a consultant for Abbott Diagnostics, Beckman-Coulter, Roche and Singulex. All other authors have nothing to declare.

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

    • Data sharing statement All data from the study are available from GitHub in comma separated value format.

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