ABC | Volume 113, Nº3, September 2019

Original Article High Residual Platelet Reactivity during Aspirin Therapy in Patients with Non-St Segment Elevation Acute Coronary Syndrome: Comparison Between Initial and Late Phases Marianna Deway Andrade Dracoulakis, 1 Paul Gurbel, 2 Marco Cattaneo, 3 Herlon Saraiva Martins, 4 José Carlos Nicolau, 4 Roberto Kalil Filho 4 Hospital da Bahia - Instituto de Ensino e Pesquisa, 1 Salvador, BA – Brazil Sinai Hospital of Baltimore - Sinai Center for Thrombosis Research, 2 Baltimore – EUA Universita Degli Studi Di Milano - Unita di Medicina III, 3 Milão – Itália Universidade de São Paulo - Faculdade de Medicina Hospital das Clínicas, 4 São Paulo, SP – Brazil Mailing Address: Marianna Deway Andrade Dracoulakis • Hospital da Bahia - Instituto de Ensino e Pesquisa - Av. Professor Magalhães Neto, 1541. Postal Code 41810-020, Salvador, BA – Brazil E-mail: madeway@hotmail.com , marianna.andrade@hospitaldabahia.com.br Manuscript received July 31, 2018, revised manuscript July 20, 2018, accepted December 19, 2018 DOI: 10.5935/abc.20190146 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. (Arq Bras Cardiol. 2019; 113(3):357-363) Keywords: Acute Coronary Syndrome; Platelet Aggregation/drug effects; Myocardial Ischemia; Aged; aspirin/therapeutic use; Aspirin/adverse effects. Introduction Acetylsalicylic acid (ASA) is widely used as first-line antiplatelet therapy for acute coronary syndromes (ACS) and is recommended by the guidelines of the American Heart Association and the American College of Cardiology, 1 European Society of Cardiology 2 and the Brazilian Society of Cardiology 3 for patients with non-ST segment elevation acute coronary syndromes (NSTE ACS). AAS has been tested with proven efficacy in several randomized clinical trials across the spectrum of both acute and chronic coronary artery disease. 4-7 However, some studies have demonstrated high variability in the individual antiplatelet response to ASA in different populations and scenarios. 8 This variability may contribute, at least in part, to the high rate of recurrence of ischemic events in patients with coronary artery disease. 9,10 The prevalence of high platelet reactivity (HPR) in patients using ASA depends, among other factors, on the laboratory test and cut-off point used, as well as on the clinical picture. In patients with chronic arterial disease, the prevalence ranges from 0 to 57% (24%, on average). 10-13 More importantly, patients with HPR have been described to have a poorer clinical outcome, with a higher incidence of serious cardiovascular events, including mortality. 10,11,14 In ACS, the estimated prevalence of HPR is supposedly higher. 15 Previous studies have suggested that atherosclerotic load and systemic inflammation may have a significant influence on platelet reactivity. 16,17 However, it is not clear whether this high prevalence of HPR is a transient acute phase phenomenon or a permanent characteristic of this 357