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Antithrombotic treatment is a key component of secondary prevention following acute coronary syndromes (ACS). Although dual antiplatelet therapy is standard therapy post-ACS, duration of treatment is the subject of ongoing debate. Prolonged dual antiplatelet therapy in high-risk patients with history of myocardial infarction reduced the risk of recurrent myocardial infarction, stroke or cardiovascular death. Similarly, in patients with stable coronary artery disease, two-thirds of whom had a history of myocardial infarction, dual antithrombotic therapy with very-low-dose rivaroxaban and aspirin also resulted in improved ischaemic outcomes. In the absence of head-to-head comparison, choosing the most appropriate treatment strategy can be challenging, particularly when it comes to balancing the risks of ischaemia and bleeding. We aim to review the evidence for currently available antithrombotic treatments and provide a practical algorithm to aid the decision-making process.

Bleeding events in relation to treatment of ST-segment elevation myocardial infarction (STEMI) have previously been associated with mortality. In this study, we investigated the incidence and prognosis of, and variables associated with serious bleedings within 30 days after primary percutaneous coronary intervention in patients from The Third Danish Study of Optimal Acute Treatment of Patients with ST-Segment Elevation Myocardial Infarction (DANAMI-3) (n = 2,217). Hospital charts were read within 30 days postadmission to assess bleeding events using thrombolysis in myocardial infarction (TIMI) and Bleeding Academic Research Consortium criteria. TIMI minor/major bleeding (TMMB) occurred in 59 patients (2.7%). Variables associated with TMMB were female gender (hazard ratio [HR] 3.9, 95% confidence interval [CI] 2.2 to 6.7, p 3 hours (HR 1.9, 95% CI 1.1 to 3.3, p = 0.02), use of glycoprotein IIb/IIIa inhibitor (HR 2.1, 95% CI 1.2 to 3.7, p = 0.01), and increasing S-creatinine (HR 1.1, 95% CI 1.0 to 1.2, p = 0.001). Undergoing 2 in-hospital procedures were not associated with increased risk of TMMB. TMMB was strongly associated with 30-day mortality in multivariable analysis (HR 4.8, 95% CI 2.2 to 10.4, p

Prasugrel and ticagrelor are next-generation antiplatelet agents that provide a rapider and more potent inhibition of platelet P2Y12 receptor than clopidogrel. In combination with aspirin, these new P2Y12 inhibitors are now the first line treatments for patients with acute coronary syndrome. However, these potent antiplatelet agents introduce a new paradigm in the daily management of antithrombotic drugs, particularly when an invasive procedure is planned. The pharmacology of these antiplatelet agents, and the results of the main clinical trials, are reviewed with a special focus on good prescription practices (indications, contra-indications, drug interactions), and on peri-operative management. Strategies are proposed for safely reducing the bleeding risk in elderly patients, in patients requiring concomitant oral anticoagulant therapy, or in patients with an increased haemorrhagic risk.

Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is a key strategy to reduce platelet reactivity and to prevent thrombotic events in patients treated with percutaneous coronary intervention. In an earlier consensus document, we proposed cutoff values for high on-treatment platelet reactivity to adenosine diphosphate (ADP) associated with post–percutaneous coronary intervention ischemic events for various platelet function tests (PFTs). Updated American and European practice guidelines have issued a Class IIb recommendation for PFT to facilitate the choice of P2Y12 receptor inhibitor in selected high-risk patients treated with percutaneous coronary intervention, although routine testing is not recommended (Class III). Accumulated data from large studies underscore the importance of high on-treatment platelet reactivity to ADP as a prognostic risk factor. Recent prospective randomized trials of PFT did not demonstrate clinical benefit, thus questioning whether treatment modification based on the results of current PFT platforms can actually influence outcomes. However, there are major limitations associated with these randomized trials. In addition, recent data suggest that low on-treatment platelet reactivity to ADP is associated with a higher risk of bleeding. Therefore, a therapeutic window concept has been proposed for P2Y12 inhibitor therapy. In this updated consensus document, we review the available evidence addressing the relation of platelet reactivity to thrombotic and bleeding events. In addition, we propose cutoff values for high and low on-treatment platelet reactivity to ADP that might be used in future investigations of personalized antiplatelet therapy.

Introdução e objetivos: Estimar os rácios custo-efetividade e custo-utilidade da utilizac¸ão deticagrelor versus clopidogrel no tratamento de doentes com síndromas coronárias agudas(angina instável, enfarte do miocárdio sem elevac¸ão ST [NSTEMI] ou enfarte do miocárdio comelevac¸ão ST [STEMI]); incluindo doentes sujeitos a tratamento médico e aqueles geridoscom intervenção coronária percutânea (ICP) ou bypass aortocoronário com enxerto (CABG). Metodologia: Foi utilizada uma árvore de decisão de curto prazo e um modelo de Markov delongo prazo para simular a progressão dos doentes no decurso da sua vida. Os dados de eficácia clínica foram recolhidos a partir do ensaio clínico PLATO e os dados de consumo de recursos foram obtidos na Contabilidade Analítica do Hospital de Santa Marta, legislação dos GDH e consulta de bibliografia disponível. Resultados: Ticagrelor proporciona, a cada doente, um incremento de 0,1276 anos de vida e0,1106 QALY. Na perspectiva da sociedade, estes ganhos implicam um aumento da despesa em 610 D . Obtêm-se, assim, um custo incremental por ano de vida salvo de 4780 D e um custo incremental por QALY de 5517 D . Conclusões: Os resultados obtidos mostram que o ticagrelor diminui a quantidade de eventos,quando comparado com clopidogrel. Os custos com ticagrelor são parcialmente compensados por uma diminuição dos custos decorrentes dos eventos evitados. Assim, a utilização de ticagrelor na prática clínica portuguesa é custo-efetiva quando comparado com a abordagem com clopidogrel., Introduction and Objectives To estimate the cost-effectiveness and cost-utility of ticagrelor in the treatment of patients with acute coronary syndromes (unstable angina or myocardial infarction with or without ST-segment elevation), including patients treated medically and those undergoing percutaneous coronary intervention or coronary artery bypass grafting. Methods A short-term decision tree and a long-term Markov model were used to simulate the evolution of patients' life-cycles. Clinical effectiveness data were collected from the PLATO trial and resource use data were obtained from the Hospital de Santa Marta database, disease-related group legislation and the literature. Results Ticagrelor provides increases of 0.1276 life years and 0.1106 quality-adjusted life years (QALYs) per patient. From a societal perspective these clinical gains entail an increase in expenditure of €610. Thus the incremental cost per life year saved is €4780 and the incremental cost per QALY is €5517. Conclusions The simulation results show that ticagrelor reduces events compared to clopidogrel. The costs of ticagrelor are partially offset by lower costs arising from events prevented. The use of ticagrelor in clinical practice is therefore cost-effective compared to generic clopidogrel.

Introduction and Objectives: To estimate the cost-effectiveness and cost-utility of ticagrelor in the treatment of patients with acute coronary syndromes (unstable angina or myocardial infarction with or without ST-segment elevation), including patients treated medically and those undergoing percutaneous coronary intervention or coronary artery bypass grafting. Methods: A short-term decision tree and a long-term Markov model were used to simulate the evolution of patients’ life-cycles. Clinical effectiveness data were collected from the PLATO trial and resource use data were obtained from the Hospital de Santa Marta database, diagnosis-related group legislation and the literature. Results: Ticagrelor provides increases of 0.1276 life years and 0.1106 quality-adjusted life years (QALYs) per patient. From a societal perspective these clinical gains entail an increase in expenditure of €610. Thus the incremental cost per life year saved is €4780 and the incremental cost per QALY is €5517. Conclusions: The simulation results show that ticagrelor reduces events compared to clopidogrel. The costs of ticagrelor are partially offset by lower costs arising from events prevented. The use of ticagrelor in clinical practice is therefore cost-effective compared to generic clopidogrel. Resumo: Introdução e objetivos: Estimar os rácios custo-efetividade e custo-utilidade da utilização de ticagrelor versus clopidogrel no tratamento de doentes com síndromas coronárias agudas (angina instável, enfarte do miocárdio sem elevação ST [NSTEMI] ou enfarte do miocárdio com elevação ST [STEMI]); incluindo doentes sujeitos a tratamento médico e aqueles geridos com intervenção coronária percutânea (ICP) ou bypass aortocoronário com enxerto (CABG). Metodologia: Foi utilizada uma árvore de decisão de curto prazo e um modelo de Markov de longo prazo para simular a progressão dos doentes no decurso da sua vida. Os dados de eficácia clínica foram recolhidos a partir do ensaio clínico PLATO e os dados de consumo de recursos foram obtidos na Contabilidade Analítica do Hospital de Santa Marta, legislação dos GDH e consulta de bibliografia disponível. Resultados: Ticagrelor proporciona, a cada doente, um incremento de 0,1276 anos de vida e 0,1106 QALY. Na perspectiva da sociedade, estes ganhos implicam um aumento da despesa em 610€. Obtêm-se, assim, um custo incremental por ano de vida salvo de 4780€ e um custo incremental por QALY de 5517€. Conclusões: Os resultados obtidos mostram que o ticagrelor diminui a quantidade de eventos, quando comparado com clopidogrel. Os custos com ticagrelor são parcialmente compensados por uma diminuição dos custos decorrentes dos eventos evitados. Assim, a utilização de ticagrelor na prática clínica portuguesa é custo-efetiva quando comparado com a abordagem com clopidogrel. Keywords: Ticagrelor, Clopidogrel, Cost-effectiveness, Cost-utility, Acute coronary syndromes, Percutaneous coronary intervention, Coronary artery bypass grafting, ST-elevation myocardial infarction, Non-ST-elevation myocardial infarction, Palavras-chave: Ticagrelor, Clopidogrel, Custo-efetividade, Custo-utilidade, Síndromas coronárias agudas, Síndroma coronária aguda, Intervenção coronária percutânea, Bypass aortocoronário com enxerto, Enfarte do miocárdio com elevação ST, Enfarte do miocárdio sem elevação ST