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Original research article
Outcomes in patients treated with ticagrelor versus clopidogrel after acute myocardial infarction stratified by renal function
  1. Robert Edfors1,2,
  2. Anders Sahlén1,2,3,
  3. Karolina Szummer1,2,
  4. Henrik Renlund4,
  5. Marie Evans5,6,
  6. Juan-Jesus Carrero7,
  7. Jonas Spaak8,
  8. Stefan K James4,
  9. Bo Lagerqvist4,
  10. Christoph Varenhorst4,
  11. Tomas Jernberg8
  1. 1 Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden
  2. 2 Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
  3. 3 National Heart Centre, Singapore, Singapore
  4. 4 Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
  5. 5 Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
  6. 6 Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden
  7. 7 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  8. 8 Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to Dr Robert Edfors, Department of Medicine, Huddinge, Karolinska Institutet, Department of Cardiology, Karolinska University Hospital, 171 76 Stockholm, Sweden; robert.edfors{at}ki.se

Abstract

Objectives We aimed to analyse outcomes of ticagrelor and clopidogrel stratified by estimated glomerular filtration rate (eGFR) in a large unselected cohort of patients with acute myocardial infarction (MI).

Methods We used follow-up data in MI survivors discharged on ticagrelor or clopidogrel enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry. The association between ticagrelor versus clopidogrel and the primary composite outcome of death, MI or stroke and the secondary outcome rehospitalisation with bleeding diagnosis at 1 year, was studied using adjusted Cox proportional hazards models, stratifying after eGFR levels.

Results In total, 45 206 patients with MI discharged on clopidogrel (n=33 472) or ticagrelor (n=11 734) were included. The unadjusted 1-year event rate for the composite endpoint of death, MI or stroke was 7.0%, 18.0% and 48.0% for ticagrelor treatment and 11.0%, 33.0% and 64.0% for clopidogrel treatment in patients with eGFR>60 (n=33 668), eGFR30–60 (n=9803) and eGFR<30 (n=1735), respectively. After adjustment, ticagrelor as compared with clopidogrel was associated with a lower 1-year risk of the composite outcome (eGFR>60: HR 0.87, 95% CI 0.76 to 99, eGFR30–60: 0.82 (0.70 to 0.97), eGFR<30: 0.95 (0.69 to 1.29), P for interaction=0.55) and a higher risk of bleeding (eGFR>60: HR 1.10, 95% CI 0.90 to 1.35, eGFR30–60: 1.13 (0.84 to 1.51), eGFR<30: 1.79 (1.00 to 3.21), P for interaction=0.30) across the eGFR strata.

Conclusions Treatment with ticagrelor as compared with clopidogrel in patients with MI was associated with lower risk for the composite of death, MI or stroke and a higher bleeding risk across all strata of eGFR. Of caution, bleeding events were more abundant in patients with eGFR<30.

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

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Footnotes

  • Contributors RE, TJ, AS, HR, SKJ and KS contributed to the design of the article. AS and HR performed data collection and HR conducted statistical analyses. ME, TJ, SKJ, CV, BL, KS, JS, J-JC, AS and RE were responsible for the interpretation of data as well as drafting and critical revision of the article. All authors approved the final version of the article to be published/submitted.

  • Funding This work was supported by a grant from the Swedish Foundation for Strategic Research. This work was also supported by the Swedish Heart and Lung Foundation and the Stockholm County Council (ALF project).

  • Competing interests CV received institutional research grants from AstraZeneca and The Medicines Company, lecture and advisory board fees from AstraZeneca, The Medicines Company and Boehringer Ingelheim, lecture fees from Bristol Myers Squibb, Pfizer and CSL Behring, and is on Clinical Endpoint Committees for Pfizer, Bristol Myers Squibb, Philips and AstraZeneca. KS received lecture fees from AstraZeneca, Aspen and St Jude. BL received institutional research grants from AstraZeneca. ME received payment for lectures for Amgen. J-JC received institutional research grants from AstraZeneca. JS received speaker honoraria from Amgen, Baxter, Astellas Pharma, AstraZeneca, MSD and Hospira. SKJ received institutional research Grant, honoraria and consultant/advisory board fee from AstraZeneca; institutional research grant and consultant/advisory board fee from Medtronic; institutional research grants and honoraria from The Medicines Company; consultant/advisory board fees from Janssen, Bayer. TJ: consulting and lecture fees from AstraZeneca, MSD and Aspen.

  • Patient consent Not required.

  • Ethics approval Regional Ethics Committee in Stockholm, Sweden.

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

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