Translation of experimental cardioprotective capability of P2Y12 inhibitors into clinical outcome in patients with ST-elevation myocardial infarction

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Marie V Hjortbak
  • Kevin K W Olesen
  • Jacob M Seefeldt
  • Thomas R Lassen
  • Rebekka V Jensen
  • ,
  • Alexander Perkins, London School of Hygiene and Tropical Medicine
  • ,
  • Matthew Dodd, London School of Hygiene and Tropical Medicine
  • ,
  • Tim Clayton, London School of Hygiene and Tropical Medicine
  • ,
  • Derek Yellon, London Ctr Nanotechnol, University College London, University of London
  • ,
  • Derek J Hausenloy, London Ctr Nanotechnol, University College London, University of London, Duke-National University of Singapore Medical School, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  • ,
  • Hans Erik Bøtker
  • CONDI-2/ERIC-PPCI Investigators

We studied the translational cardioprotective potential of P2Y12 inhibitors against acute myocardial ischemia/reperfusion injury (IRI) in an animal model of acute myocardial infarction and in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). P2Y12 inhibitors may have pleiotropic effects to induce cardioprotection against acute myocardial IRI beyond their inhibitory effects on platelet aggregation. We compared the cardioprotective effects of clopidogrel, prasugrel, and ticagrelor on infarct size in an in vivo rat model of acute myocardial IRI, and investigated the effects of the P2Y12 inhibitors on enzymatic infarct size (48-h area-under-the-curve (AUC) troponin T release) and clinical outcomes in a retrospective study of STEMI patients from the CONDI-2/ERIC-PPCI trial using propensity score analyses. Loading with ticagrelor in rats reduced infarct size after acute myocardial IRI compared to controls (37 ± 11% vs 52 ± 8%, p < 0.01), whereas clopidogrel and prasugrel did not (50 ± 11%, p > 0.99 and 49 ± 9%, p > 0.99, respectively). Correspondingly, troponin release was reduced in STEMI patients treated with ticagrelor compared to clopidogrel (adjusted 48-h AUC ratio: 0.67, 95% CI 0.47-0.94). Compared to clopidogrel, the composite endpoint of cardiac death or hospitalization for heart failure within 12 months was reduced in STEMI patients loaded with ticagrelor (HR 0.63; 95% CI 0.42-0.94) but not prasugrel (HR 0.84, 95% CI 0.43-1.63), prior to PPCI. Major adverse cardiovascular events did not differ between clopidogrel, ticagrelor, or prasugrel. The cardioprotective effects of ticagrelor in reducing infarct size may contribute to the clinical benefit observed in STEMI patients undergoing PPCI.

OriginalsprogEngelsk
Artikelnummer36
TidsskriftBasic Research in Cardiology
Vol/bind116
Nummer1
ISSN0300-8428
DOI
StatusUdgivet - dec. 2021

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