High Residual Platelet Reactivity during Aspirin Therapy in Patients with Non-St Segment Elevation Acute Coronary Syndrome: Comparison Between Initial and Late Phases / Alta Atividade Plaquetária Residual em Resposta ao Ácido Acetilsalicílico na Síndrome Coronariana Aguda Sem Supra de ST: Comparação entre as Fases Aguda e Tardia

Abstract Background: High platelet reactivity (HPR) during therapy with acetylsalicylic acid (ASA) is a poor prognostic factor in acute coronary syndromes (ACS). The prevalence of HPR during ACS is greater than that reported in stable diseases. However, it is unclear whether this prevalence of HPR is a transient phenomenon or a characteristic of this high-risk population. Objective: The main objective is to compare the effects of ASA on platelet function in the initial and late phases of ACS in a single population. Secondary objectives are: correlation between the tests between themselves and the relationship between the tests and the variation of the inflammatory markers (C-reactive protein and interleukin-6). Methods: Seventy patients with non-ST segment elevation (NSTE) ACS in use of 100-200 mg of ASA per day for at least 7 days were prospectively studied. Platelet function was assessed in the first 48 hours and subsequently after 3 months using four methods: VerifyNow™ (VFN), whole blood platelet aggregation (WBPA) with arachidonic acid (AA) and collagen as agonists, and platelet function analyzer (PFA). The level of statistical significance considered was < 0.05. Results: According to the more specific methods (WBPA with AA and VFN), the incidence of HPR was significantly higher in the early phase than in the late phase: WBPA with AA: 31% versus 13%, p = 0.015; VFN: 32% versus 16%, p = 0.049. The other methods tested, which were less specific for ASA, did not show significant differences between phases. The correlation between the methods was weak or moderate (r ranging from 0.3 to 0.5, p < 0.05), and there were no significant associations between HPR and inflammatory markers. Conclusion: The prevalence of HPR during AAS therapy, assessed by specific methods for cyclooxygenase 1 (COX-1), is higher during the acute phase than in the late phase of NSTE ACS.

Resumo Fundamento: A alta atividade plaquetária (AAP) durante a terapia com ácido acetilsalicílico (AAS) é fator de mau prognóstico nas síndromes coronarianas agudas (SCA). A prevalência de AAP durante a SCA é maior do que a relatada na doença estável. No entanto, não está claro se esta prevalência de AAP é um fenômeno transitório ou característica dessa população de alto risco. Objetivo: O objetivo principal é comparar, em uma mesma população, os efeitos do AAS sobre a função plaquetária nas fases inicial e tardia da SCA. Os objetivos secundários são: correlação entre os testes entre si e a relação entre os testes e a variação dos marcadores inflamatórios (proteína C reativa e interleucina-6). Métodos: Foram estudados prospectivamente 70 pacientes com SCA sem elevação de ST (SCSST) em uso de 100 a 200 mg de AAS por dia por pelo menos 7 dias. A função plaquetária foi avaliada nas primeiras 48 horas e 3 meses após por quatro métodos: VerifyNow™ (VFN), agregometria de sangue total (AST) com ácido araquidônico (AA) e colágeno como agonistas, e analisador de função plaquetária (PFA). O nível de significância estatístico considerado foi < 0,05. Resultados: A média de idade foi de 65 ±9,7 anos e 54% da população eram do sexo feminino. De acordo com os métodos mais específicos (AST com AA e VFN), a incidência de AAP foi significativamente maior na fase inicial, em relação à tardia: AST com AA 31% versus 13%, p = 0,015; VFN 32% versus 16%, p = 0,049. Os outros métodos testados, menos específicos para o AAS, não mostraram diferenças significativas entre as fases. A correlação entre os métodos foi fraca ou moderada (r variando de 0,3 a 0,5, p < 0,05), e não houve associações significativas entre AAP e marcadores inflamatórios. Conclusão: A prevalência de AAP durante a terapia com AAS, avaliada por métodos específicos para cicloxigenase 1 (COX-1), é maior durante a fase aguda do que na tardia da SCASST.

Aspirin and clopidogrel response variability: review of the published literature.

Antiplatelet resistance has been proposed as a possible mechanism to explain recurrent cardiovascular events in patients who have coronary artery disease and who are undergoing dual antiplatelet therapy. A comprehensive search on PubMed was conducted for literature that was printed in the English language between January 1996 and November 2007 on aspirin and clopidogrel resistance. Significant traits for aspirin hyporesponsiveness were female sex, older age, and lower levels of hemoglobin. Diabetes mellitus and elevated body mass index showed trends toward a higher incidence of resistance in some aspirin trials but did not reach statistical significance. Clopidogrel studies suggested that patients with type-2 diabetes mellitus are more likely to manifest inadequate response to the medication. Although 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors were initially suspected to decrease response to clopidogrel, later studies refuted this possibility. Patients with a suboptimal response to aspirin or clopidogrel seem to be at increased risk of recurrent cardiovascular events. Large clinical trials with standardized laboratory methods and well-defined protocols are needed to determine whether common features exist in patients with suspected hyporesponsiveness to antiplatelet therapy, and to validate the clinical relevance of response variability. A concise nonarbitrary definition of physiologic "resistance" is needed, and investigators should identify patients as having a variable response to antiplatelet therapy.