Abstract
Background
Robust comparisons between oral P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor)
in ST-elevation myocardial infarction (STEMI) patients who undergo primary percutaneous
coronary intervention are lacking. We sought to evaluate outcomes on the basis of
P2Y12 inhibitor therapy in patients from the Thrombectomy With PCI Versus PCI Alone in Patients With STEMI Undergoing Primary PCI (TOTAL) trial.
Methods
We grouped 9932 patients according to P2Y12 inhibitor at hospital discharge: clopidogrel
(n = 6500; 65.5%), prasugrel (n = 1244; 12.5%), or ticagrelor (n = 2188; 22.0%). The
primary composite end point of cardiovascular death, recurrent myocardial infarction,
cardiogenic shock, or New York Heart Association class IV heart failure was examined
at 1 year. Secondary efficacy and safety end points were also assessed. Cox proportional
hazard ratios were determined and adjusted for confounders via propensity scoring.
Results
Baseline characteristics differing between the 3 groups were mainly age 75 years or
older, diabetes, and previous stroke. After adjustment, ticagrelor use was associated
with a lower rate of the primary composite outcome compared with clopidogrel (adjusted
hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.57-0.91; P < 0.02) and prasugrel (aHR, 0.65; 95% CI, 0.48-0.89; P = 0.02). Prasugrel use was not associated with a lower rate of the primary outcome
compared with clopidogrel (aHR, 1.09; 95% CI, 0.86-1.39; P > 0.99). Neither prasugrel nor ticagrelor were associated with increased risk of
stroke compared with clopidogrel. Compared with clopidogrel, ticagrelor was associated
with significantly lower rates of major bleeding.
Conclusions
In this observational analysis of STEMI patients who underwent primary percutaneous
coronary intervention, ticagrelor was associated with improved outcomes compared with
clopidogrel and prasugrel. An appropriately powered randomized trial is needed to
confirm these findings.
Résumé
Contexte
Il n’existe pas d’analyse robuste comparant les inhibiteurs P2Y12 à prise orale (clopidogrel,
prasugrel et ticagrélor) chez les patients ayant subi un infarctus du myocarde avec
élévation du segment ST (STEMI) traités par une intervention coronaire percutanée
(ICP) primaire. Nous avons entrepris d’évaluer les résultats chez les patients ayant
reçu un traitement par un inhibiteur P2Y12 dans le cadre de l’essai TOTAL (Thrombectomy With PCI Versus PCI Alone in Patients With STEMI Undergoing Primary PCI).
Méthodologie
Nous avons réparti 9 932 patients en trois groupes en fonction de l’inhibiteur P2Y12
qui leur a été prescrit à leur sortie de l’hôpital : clopidogrel (n = 6 500; 65,5
%), prasugrel (n = 1 244; 12,5 %) ou ticagrélor (n = 2 188; 22,0 %). Le critère d’évaluation
principal, composé du décès d’origine cardiovasculaire, d’un nouvel infarctus du myocarde,
d’un choc cardiogénique ou d’une insuffisance cardiaque de classe IV selon la New
York Heart Association, a été évalué après 1 an. Des critères d’efficacité et d’innocuité
secondaires ont aussi été évalués. Les rapports des risques proportionnels selon le
modèle de Cox ont été calculés et corrigés au moyen d’une analyse des scores de propension
pour tenir compte des facteurs de confusion.
Résultats
Les sujets des trois groupes se distinguaient par certaines caractéristiques initiales,
soit l’âge (75 ans ou plus), la présence de diabète et les antécédents d’accident
vasculaire cérébral (AVC). Après correction, l’emploi du ticagrélor a été associé
à un taux inférieur de survenue de l’un ou l’autre des événements du critère d’évaluation
principal comparativement au clopidogrel (rapport des risques instantanés corrigé
[RRIc] de 0,72; intervalle de confiance [IC] à 95 %, de 0,57 à 0,91; p < 0,02) et au prasugrel (RRIc de 0,65; IC à 95 %, de 0,48 à 0,89; p = 0,02). L’emploi du prasugrel n’a pas été associé à un taux inférieur de survenue
de l’un des événements du critère principal comparativement au clopidogrel (RRIc de
1,09; IC à 95 %, de 0,86 à 1,39; p > 0,99). Ni le prasugrel ni le ticagrélor n’ont été associés à un risque accru d’AVC
comparativement au clopidogrel. Enfin, le ticagrélor a été associé à des taux d’hémorragie
majeure significativement inférieurs comparativement au clopidogrel.
Conclusions
Dans le cadre de notre analyse observationnelle des patients ayant subi un STEMI et
traités par intervention coronaire percutanée primaire, les résultats obtenus avec
le ticagrélor se sont révélés supérieurs à ceux obtenus avec le clopidogrel ou avec
le prasugrel. La réalisation d’une étude avec répartition aléatoire d’une puissance
suffisante s’impose pour confirmer ces observations.
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Article info
Publication history
Published online: May 07, 2019
Accepted:
April 23,
2019
Received:
December 18,
2018
Footnotes
See editorial by Marquis-Gravel et al., pages 1283–1285 of this issue.
See page 1384 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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Access this article on ScienceDirectLinked Article
- “Ticagrelor or Prasugrel, Doctor?” The Basis for Decision in Clinical PracticeCanadian Journal of CardiologyVol. 35Issue 10
- PreviewSelecting the best long-term antithrombotic regimen after ST-segment elevation myocardial infarction (STEMI) in patients treated with the use of primary percutaneous coronary intervention (pPCI) is complex. An exponentially growing body of literature provides clinicians with validated tools to support individualization of dual-antiplatelet therapy (DAPT) strategies based on patients’ characteristics to optimize the trade-off between ischemia and bleeding.1 Huge strides have been made to tailor antithrombotic management after STEMI, yet the answer to a simple conundrum encountered by cardiologists on a daily basis remains elusive: “Ticagrelor or prasugrel, doctor?”
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