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CYP2C19 genotyping is feasible in everyday clinical practice, both in the acute and non-acute settings.

Background: Guidelines favor ticagrelor or prasugrel over clopidogrel in patients with myocardial infarction. However, the POPular Genetics trial (Patient Outcome After Primary Percutaneous Coronary Intervention [PCI]) showed that in patients with primary PCI, a CYP2C19 genotype–guided strategy was associated with a lower bleeding risk without increasing thrombotic risk, compared with routine ticagrelor/prasugrel treatment. Nevertheless, optimal P2Y 12 inhibitor treatment in specific CYP2C19 genetic subgroups is still a subject of debate. Methods: A prespecified subanalysis of the POPular Genetics trial was performed, using patients in whom CYP2C19 *2, *3, and *17 genotypes was determined. Two different analyses were planned. The first assessed the effect of the CYP2C19 *17 allele in clopidogrel-treated patients. The second compared the effect of clopidogrel in noncarriers of a loss-of-function allele with ticagrelor/prasugrel–treated patients, irrespective of CYP2C19 genotype. Main outcomes were a thrombotic outcome (cardiovascular death, myocardial infarction, stent thrombosis, and stroke) and a bleeding outcome (PLATO [Platelet Inhibition and Patient Outcomes] major and minor bleeding) after 12 months. Results: A total of 2429 patients were used for analyses. In the first analysis, the CYP2C19 *17 polymorphism was not found to have a significant influence on thrombotic (adjusted hazard ratio, 0.95 [95% CI, 0.45–2.02]) or bleeding outcomes (adjusted hazard ratio, 0.74 [95% CI, 0.48–1.18]). In the second analysis, clopidogrel was associated with a lower number of bleeding events compared with ticagrelor/prasugrel (9.9% versus 11.7%, adjusted hazard ratio, 0.74 [95% CI, 0.56–0.96]), without a significant increase in thrombotic events (3.4% versus 2.5%, adjusted hazard ratio, 1.14 [95% CI, 0.68–1.90]). Conclusions: In patients with primary PCI not carrying a CYP2C19 loss-of-function allele, the use of clopidogrel compared with ticagrelor or prasugrel was associated with lower bleeding rates, without an increase in thrombotic events. No effect on clinical outcomes was found for the CYP2C19 *17 polymorphism. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01761786. URL: https://www.trialregister.nl/ ; Unique identifier: NL2872.

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Objective This study aims to determine frequency and reasons for prematurely discontinuing or switching antiplatelet therapy in elderly patients admitted with non-ST-elevation acute coronary syndrome (NSTE-ACS). Method Patients of 75 years or older admitted with suspected NSTE-ACS were included between 2013 and 2016. Information was extracted from the patients’ medical files. Results A total of 544 patients were included, 17.3% discontinued aspirin within one year, predominantly (57%) within 30 days. The most common reason was the start of a (non-vitamin-K) oral anticoagulant [(N)OAC], either combined with a P2Y12-inhibitor (43%) or as monotherapy (16%). The P2Y12-inhibitor was discontinued in 31.2% of patients within one year, of which 46% within 30 days. The most common reason was undergoing coronary artery bypass grafting (CABG; 22%). Switching of clopidogrel seldom occurred; however, ticagrelor was switched in 50/179 patients mainly due to dyspnoea (42%). Independent predictors for prematurely discontinuing antiplatelet therapy were undergoing CABG [odds ratio (OR) 3.257 (95% confidence interval [CI] 1.836–5.779)], need for (N)OAC [OR 2.167 (95% CI 1.423–3.300)] and type II ACS as final diagnosis [OR 3.793 (95% CI 1.721–8.361)]. Undergoing percutaneous coronary intervention [OR 0.393 (95% CI 0.243–0.634)] and use of clopidogrel [OR 0.441(95% CI 0.293–0.662)] were independent predictors of continuing antiplatelet therapy. Conclusion In elderly patients of at least 75 years with NSTE-ACS, antiplatelet therapy is frequently discontinued prematurely, most often within 30 days. Main reasons for discontinuing are need for (N)OAC, undergoing CABG or type II ACS as final diagnosis and suffering from dyspnoea while on ticagrelor.

IntroductionThe POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y 12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI). Objective In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel. Methods A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y 12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y 12 inhibitors, and equal distribution of thrombotic events between the two strategies). Results Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and €725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant. ConclusionIn patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings. Trial Registration Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872 Pim W. M. van Dorst, Gerrit J. A. Vos have contributed equally to this work.

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A significant number of patients with atrial fibrillation, treated with oral anticoagulants, present with an acute coronary syndrome. Many of these patients have an indication for coronary angiography. The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) and the novel P2Y12 inhibitors has generated new uncertainty about the optimal treatment regimen, whether triple or dual therapy should be given and which is the most beneficial P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel). In this article, we will summarise the practical advice on the management of acute coronary syndrome patients requiring oral anticoagulants following the recent consensus document of the European Society of Cardiology (ESC) Working Group on Thrombosis in association with the European Heart Rhythm Association (EHRA) and ESC guidelines.