Coronary interventions

Enhanced platelet inhibition by clopidogrel and risk of bleeding in patients requiring oral anticoagulation after drug-eluting stent implantation

EuroIntervention 2019;15:700-706. DOI: 10.4244/EIJ-D-18-00995

Alexander Goedel
Alexander Goedel1, MD; Katrin A. Fiedler2, MD; Julinda Mehilli3,4, MD; Isabell Bernlochner1, MD; Gesa von Olshausen1, MD; Katharina Mayer2, MD; Stefanie Schüpke2,4, MD; Petra Hoppmann1, MD; Dirk Sibbing3,4, MD; Michael Maeng5, MD; Steffen Massberg3,4, MD; Heribert Schunkert2,4, MD; Karl-Ludwig Laugwitz1,4, MD; Adnan Kastrati2,4, MD; Nikolaus Sarafoff2, MD
1. Klinik und Poliklinik für Innere Medizin I, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany; 2. Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum der Technischen Universität München, Munich, Germany; 3. Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians Universität, Munich, Germany; 4. DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany; 5. Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark

Aims: Clopidogrel is the P2Y12 inhibitor of choice in patients who undergo PCI and have an indication for oral anticoagulation (OAC). Prediction of the bleeding risk is of major interest in this population. The aim of this analysis was to investigate whether an enhanced platelet inhibition by clopidogrel measured by platelet function testing (PFT) with the Multiplate Analyzer is associated with an increased bleeding risk in patients on triple antithrombotic therapy.

Methods and results: This investigation was performed in a cohort of 524 patients from the randomised ISAR-TRIPLE trial; 458 (87.4%) had PFT results available in the first 24 hours after PCI. Patients belonging to the lowest quintile according to PFT were considered as enhanced responders to clopidogrel. The primary endpoint was major bleeding according to TIMI criteria at nine months. The median of ADP-induced platelet aggregation in the whole population was 163 AU*min (107-241). Patients in the lowest quintile had values below 93 AU*min. These enhanced responders (92 patients) had a significantly higher risk of TIMI major bleeding (hazard ratio [HR] 3.13, 95% confidence interval [CI]: 1.38-7.09, p=0.01) and overall mortality (HR 3.42, 95% CI: 1.55-7.52, p=0.004) compared with the remaining patients (366 patients). No significant difference was observed for the secondary combined ischaemic endpoint (HR 1.27, 95% CI: 0.47-3.47, p=0.64).

Conclusions: Enhanced platelet inhibition delivered by clopidogrel is associated with an increased risk for major bleeding and death in patients on OAC who undergo PCI. These results support the use of PFT to identify patients with an increased risk for bleeding.

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drug-eluting stentadjunctive pharmacotherapyatrial fibrillation
Coronary interventionsSTEMINSTEMIStable CAD
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