2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS).

Clopidogrel therapy improves cardiovascular outcomes in patients with acute coronary syndromes and following percutaneous coronary intervention by inhibiting adenosine diphosphate (ADP)-dependent platelet activation. However, nonresponsiveness is widely recognized and is related to recurrent ischemic events. To identify gene variants that influence clopidogrel response. In the Pharmacogenomics of Antiplatelet Intervention (PAPI) Study (2006-2008), we administered clopidogrel for 7 days to 429 healthy Amish persons and measured response by ex vivo platelet aggregometry. A genome-wide association study was performed followed by genotyping the loss-of-function cytochrome P450 (CYP) 2C19*2 variant (rs4244285). Findings in the PAPI Study were extended by examining the relation of CYP2C19*2 genotype to platelet function and cardiovascular outcomes in an independent sample of 227 patients undergoing percutaneous coronary intervention. ADP-stimulated platelet aggregation in response to clopidogrel treatment and cardiovascular events. Platelet response to clopidogrel was highly heritable (h(2) = 0.73; P < .001). Thirteen single-nucleotide polymorphisms on chromosome 10q24 within the CYP2C18-CYP2C19-CYP2C9-CYP2C8 cluster were associated with diminished clopidogrel response, with a high degree of statistical significance (P = 1.5 x 10(-13) for rs12777823, additive model). The rs12777823 polymorphism was in strong linkage disequilibrium with the CYP2C19*2 variant, and was associated with diminished clopidogrel response, accounting for 12% of the variation in platelet aggregation to ADP (P = 4.3 x 10(-11)). The relation between CYP2C19*2 genotype and platelet aggregation was replicated in clopidogrel-treated patients undergoing coronary intervention (P = .02). Furthermore, patients with the CYP2C19*2 variant were more likely (20.9% vs 10.0%) to have a cardiovascular ischemic event or death during 1 year of follow-up (hazard ratio, 2.42; 95% confidence interval, 1.18-4.99; P = .02). CYP2C19*2 genotype was associated with diminished platelet response to clopidogrel treatment and poorer cardiovascular outcomes.

Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose.

Few data document current cardiovascular (CV) event rates in stable patients with atherothrombosis in a community setting. Differential event rates for patients with documented coronary artery disease (CAD), cerebrovascular disease (CVD), or peripheral arterial disease (PAD) or those at risk of these diseases have not been previously evaluated in a single international cohort. To establish contemporary, international, 1-year CV event rates in outpatients with established arterial disease or with multiple risk factors for atherothrombosis. The Reduction of Atherothrombosis for Continued Health (REACH) Registry is an international, prospective cohort of 68 236 patients with either established atherosclerotic arterial disease (CAD, PAD, CVD; n = 55 814) or at least 3 risk factors for atherothrombosis (n = 12 422), who were enrolled from 5587 physician practices in 44 countries in 2003-2004. Rates of CV death, myocardial infarction (MI), and stroke. As of July 2006, 1-year outcomes were available for 95.22% (n = 64 977) of participants. Cardiovascular death, MI, or stroke rates were 4.24% overall: 4.69% for those with established atherosclerotic arterial disease vs 2.15% for patients with multiple risk factors only. Among patients with established disease, CV death, MI, or stroke rates were 4.52% for patients with CAD, 6.47% for patients with CVD, and 5.35% for patients with PAD. The incidences of the end point of CV death, MI, or stroke or of hospitalization for atherothrombotic event(s) were 15.20% for CAD, 14.53% for CVD, and 21.14% for PAD patients with established disease. These event rates increased with the number of symptomatic arterial disease locations, ranging from 5.31% for patients with risk factors only to 12.58% for patients with 1, 21.14% for patients with 2, and 26.27% for patients with 3 symptomatic arterial disease locations (P<.001 for trend). In this large, contemporary, international study, outpatients with established atherosclerotic arterial disease, or at risk of atherothrombosis, experienced relatively high annual CV event rates. Multiple disease locations increased the 1-year risk of CV events.