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Original research
Antiplatelet therapy in patients with myocardial infarction without obstructive coronary artery disease
  1. Matthias Bossard1,
  2. Peggy Gao2,
  3. William Boden3,4,
  4. Gabriel Steg5,
  5. Jean-Francois Tanguay6,
  6. Cam Joyner7,
  7. Christopher B Granger8,
  8. Adnan Kastrati9,
  9. David Faxon10,
  10. Andrzej Budaj11,
  11. Prem Pais12,
  12. Giuseppe Di Pasquale13,
  13. Vicent Valentin14,
  14. Marcus Flather15,
  15. Tiziano Moccetti16,
  16. Salim Yusuf2,17,
  17. Shamir R Mehta2,18
  1. 1Cardiology Division, Heart Center - Luzerner Kantonsspital, Luzern, Switzerland
  2. 2Population Health Research Institute (PHRI), Hamilton, Ontario, Canada
  3. 3Medicine, VA Boston Health Care System West Roxbury Campus, West Roxbury, Massachusetts, USA
  4. 4Boston University School of Medicine, Boston, Massachusetts, USA
  5. 5Cardiology Department, Hôpital Bichat-Claude Bernard, Paris, France
  6. 6Montreal Heart Institute, Montreal, Quebec, Canada
  7. 7Sunnybrook Health Sciences, University of Toronto, Toronto, Ontario, Canada
  8. 8Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
  9. 9Deutsches Herzzentrum, Munich, Germany
  10. 10Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  11. 11Department of Cardiology, Grochowski Hospital, Warsaw, Poland
  12. 12Division of Clinical Research & Training, St John's Medical College and Research Institute, Bangalore, India
  13. 13Department of Cardiology, Maggiore Hospital Carlo Alberto Pizzardi, Bologna, Emilia-Romagna, Italy
  14. 14Unidad Coronaria, Hospital Universitario Dr Peset, Valencia, Comunitat Valenciana, Spain
  15. 15Norwich Medical School, University of East Anglia, Norwich, UK
  16. 16Cardiology, Cardiocentro, Lugano, Switzerland
  17. 17Medicine, McMaster University, Hamilton, Ontario, Canada
  18. 18Division of Cardiology, Hamilton General Hospital, Hamilton, Ontario, Canada
  1. Correspondence to Dr Shamir R Mehta, Division of Cardiology, Hamilton General Hospital, Hamilton, Ontario ON L8L 2X2, Canada; smehta{at}mcmaster.ca

Abstract

Objective Approximately 10% of patients with myocardial infarction (MI) have no obstructive coronary artery disease. The prognosis and role of intensified antiplatelet therapy in those patients were evaluated.

Methods We analysed data from the Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events–Seventh Organisation to Assess Strategies in Ischaemic Symptoms trial randomising patients with ACS referred for early intervention to receive either double-dose (600 mg, day 1; 150 mg, days 2–7; then 75 mg/day) or standard-dose (300 mg, day 1; then 75 mg/day) clopidogrel. Outcomes in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) versus those with obstructive coronary artery disease (CAD) and their relation to standard-dose versus double-dose clopidogrel were evaluated. The primary outcome was cardiovascular (CV) death, MI or stroke at 30 days.

Results We included 23 783 patients with MI and 1599 (6.7%) with MINOCA. Patients with MINOCA were younger, presented more frequently with non-ST-segment elevation MI and had fewer comorbidities. All-cause mortality (0.6% vs 2.3%, p=0.005), CV mortality (0.6% vs 2.2%, p=0.006), repeat MI (0.5% vs 2.3%, p=0.001) and major bleeding (0.6% vs 2.4%, p<0.0001) were lower among patients with MINOCA than among those with obstructive CAD. Among patients with MINOCA, 2.1% of patients in the double-dose clopidogrel group and 0.6% in the standard-dose group experienced a primary outcome (HR 3.57, 95% CI 1.31 to 9.76), whereas in those with obstructive CAD, rates were 4.3% and 4.7%, respectively (HR 0.91, 95% CI 0.80 to 1.03; p value for interaction=0.011).

Conclusions Patients with MINOCA are at lower risk of recurrent CV events compared with patients with MI with obstructive CAD. Compared with a standard clopidogrel-based dual antiplatelet therapy (DAPT) regimen, an intensified dosing strategy appears to offer no additional benefit with a signal of possible harm. Further randomised trials evaluating the effects of potent DAPT in patients with MINOCA are warranted.

Trial registration number NCT00335452.

  • acute coronary syndromes
  • acute myocardial infarction
  • coronary artery disease

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Footnotes

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  • Presented at An abstract of this study was presented at the European Society of Cardiology Congress 2019 in Paris (https://academic.oup.com/eurheartj/article-abstract/40/Supplement_1/ehz748.0145/5596076?redirectedFrom=fulltext).

  • Contributors MB: conceptualisation, methodology, validation, formal analysis, writing (original draft), visualisation; PG: conceptualisation, methodology, software, validation, formal analysis, data curation, writing (review and editing); WB: investigation, data curation, writing (review and editing); GS: investigation, data curation, writing (review and editing); J-FT: investigation, writing (review and editing); CJ: investigation, writing (review and editing); CBG and DF: investigation, data curation, writing (review and editing); AK, AB, PP, GDP, VV, MF and TM: investigation, writing (review and editing); SY: investigation, methodology, resources, data curation, writing (review and editing), project administration, funding acquisition; SRM: conceptualisation, methodology, validation, investigation, resources, data curation, writing (original draft), supervision, project administration, funding acquisition. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

  • Funding The CURRENT-OASIS 7 trial was sponsored by Sanofi and Bristol-Myers Squibb.

  • Competing interests MB received research grants from the University of Basel, the Freie Akademische Gesellschaft Basel and Bangerter-Rhyner Stiftung, consulting and speaking fees from Astra-Zeneca, Bayer and Amgen. PG received research grants from Amarin, Bayer, Merck, Sanofi, and Servier and speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer-Ingelheim, Bristol-Myers-Squibb, Idorsia, Lilly, Merck, Novartis, Novo-Nordisk, Pfizer, Regeneron, Sanofi and Servier. CBG reports grants from Duke University, grants and personal fees from Sanofi Aventis, grants and personal fees from Bristol Myers Squibb during the conduct of the study. AB received investigator’s, consulting and speaking fees from Sanofi-Aventis, Bristol-Myers Squibb and AstraZeneca.

  • Patient consent for publication Not required.

  • Ethics approval The trial complied with the Declaration of Helsinki. It was approved by national regulatory authorities and the ethics committees at the participating centres. All patients provided written informed consent (ClinicalTrials.gov).

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

  • Data availability statement Data are available upon reasonable request.

  • 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.

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