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This editorial refers to ‘Clopidogrel reloading in patients undergoing percutaneous coronary intervention on chronic clopidogrel therapy. Results of the ARMYDA-4 RELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) randomized trial’, by S. Di Sciascio et al. doi:10.1093/eurheartj/ehq081 Percutaneous coronary intervention (PCI) has become the predominant form of coronary revascularization in Europe and the USA. Although overall a safe procedure, PCI may be complicated by adverse events, with myocardial infarction (MI) and bleeding being the most frequent and important contributors to mortality and morbidity after the procedure. It is estimated that ∼25% of patients undergoing PCI may have significant post-procedural myonecrosis, as identified by creatinine kinase (CK) and CK-MB isoenzyme elevations, and that up to 50% of PCI patients develop post-procedural troponin elevations.1 The development of strategies that help prevent post-procedural MI has therefore been a major research interest in the field of interventional cardiology.Ever since the late 1990s, it is generally accepted that platelets, adhering and aggregating at sites of endothelial injury and mechanical plaque disruption, are the key determinants of PCI-related myocardial necrosis. Accordingly, several trials, including the Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial,2 demonstrated that dual antiplatelet therapy with aspirin plus thienopyridines is efficient in reducing post-PCI ischaemic complications. Since then, dual antiplatelet therapy with the thienopyridine clopidogrel and aspirin has become an integral part of PCI treatment of patients presenting with various forms of coronary artery disease—ST elevation myocardial infarction (STEMI), non-ST elevation acute coronary syndrome (NSTE ACS), and stable angina.An important limitation of clopidogrel, however, lies in its pharmacokinetic and pharmacodynamic properties.3 Clopidogrel is a prodrug that has to undergo two sequential cytochrome P-450 (CYP)-dependent oxidation steps after intestinal absorption in order to be converted into its active metabolite. This leads to delayed onset of action and interindividual … *Corresponding author. Tel: + 49 89 12184578, Fax: +49 89 12184053, Email: kastrati{at}dhm.mhn.de

Is it naive to load only clopidogrel-naive patients prior to PCI?