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Dual antiplatelet therapy (DAPT) with aspirin and an oral P2Y12 inhibitor is a successful strategy for preventing recurrent ischaemic events following acute coronary syndromes (ACS). Clopidogrel was previously the P2Y12 inhibitor of choice but interpatient heterogeneity in levels of achieved platelet inhibition and delayed onset of action limit its efficacy. Consequently, the more potent P2Y12 inhibitors prasugrel and ticagrelor have been compared with clopidogrel in randomised controlled trials (RCT) of patients with ACS. In Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38, prasugrel significantly reduced recurrent ischaemic events in moderate to high risk patients managed with percutaneous coronary intervention (PCI) but increased major bleeding. In PLATelet inhibition and patient Outcomes (PLATO), ticagrelor significantly reduced rates of vascular death, myocardial infarction (MI) and stroke at 12 months, without increasing overall major or fatal bleeding but with more non-coronary artery bypass grafting-related bleeding. Given their superior ischaemic risk reduction, international guidelines now preferentially recommend prasugrel and ticagrelor use in patients with ST-elevation MI (STEMI) and non-STEMI without contraindications, except in those requiring oral anticoagulant therapy.1
Scepticism over the applicability of these findings to real-world settings remains since patients in RCTs can be highly selected due to rigorous exclusion criteria. Elderly patients and others with extensive comorbidity are often under-represented, calling into question the external validity of DAPT RCTs in these high-risk groups. Such concerns may result in underuse of guideline-recommended therapy. However, the perception that DAPT RCTs are not representative of patients managed invasively for ACS may be incorrect. Complementary real-world data have supported the RCT findings. Analysis of 45 073 patients with ACS, identified from the System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, demonstrated a lower incidence of the combined endpoint of death, MI …
Contributors ENCO drafted the article which was critically revised by RFS and WAEP.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests RFS: institutional research grants/support from AstraZeneca and PlaqueTec; consultancy fees from AstraZeneca, Actelion, Avacta, Bayer, Bristol Myers Squibb/Pfizer, Idorsia, Novartis, PlaqueTec, and The Medicines Company; speaker fees from AstraZeneca and Bayer.
Patient consent Not required.
Provenance and peer review Commissioned; internally peer reviewed.