ABC | Volume 113, Nº3, September 2019

Original Article Dracoulakis et al. High platelet activity during ASA use in ACS Arq Bras Cardiol. 2019; 113(3):357-363 high risk population, since, to the best of our knowledge, no study has analyzed the response to ASA during the acute and chronic phases in the same population. The present study was designed to give a definitive answer on this important question. Methods Study population Prospective inclusion of 70 consecutive patients admitted to the emergency department (ED) of a tertiary cardiology hospital with a diagnosis of NSTE ACS, with initial evaluation at admission (acute phase) and subsequently 3 months after discharge (late phase). Patients were considered eligible for inclusion if aged ≥ 18 years, had been diagnosed with unstable angina or non-ST segment elevation myocardial infarction within the first 48 hours of clinical onset, and were using 100 mg to 200 mg of AAS for at least 7 days prior to the event. The main exclusion criteria were the use of another antiplatelet agent in addition to ASA, oral or parenteral anticoagulation, percutaneous coronary intervention (PCI) in the last 30 days ormyocardial revascularization surgery in the last 90 days. Other exclusion criteria were hemoglobin < 10 g/dL; platelets < 100,000/mm 3 or > 500,000/mm 3 ; creatinine clearance < 30 mL/min; decompensated heart failure (Killip III or IV); current use of inotropes or vasopressors; and known hematological or neoplastic diseases. Model Patients were evaluated at two different moments: initially, at admission to ED, prior to the administration of any other antithrombotic treatment except ASA, and 3 months after hospital discharge, when they should also be on ASA as the only antiplatelet agent. At each evaluation, patients were evaluated and interviewed, and underwent blood collection 1 to 4 hours after the use of ASA. Adherence to ASA treatment was systematically evaluated during face-to-face medical interviews. The study is in accordance with the Helsinki Declaration and was approved by the local Ethics Committee; patients provided their informed consent. Objectives The primary objective of the study was to compare platelet aggregation in patients with NSTE ACS in the acute phase (the first 48 hours of the clinical picture) in relation to the late phase (3 months after) using four different methods of evaluating platelet aggregation: VerifyNow™ aspirin (VFN) (Accumetrics, Inc., San Diego, California, USA); whole blood platelet aggregation (WBPA) using arachidonic acid (AA) (Sigma-Aldrich, Saint Louis, Missouri, USA) and collagen (Chrono-Log®; Chrono-Log Co., Havertown, Pennsylvania, USA); PFA-100® Platelet Function Analyzer with collagen/ADP cartridge (COL/EPI) (Siemens Healthcare Diagnostics, Newark, Delaware, USA). Secondary objectives were the correlation between the four tests in the acute phase and the relationship between each of the tests with inflammatory markers (C-reactive protein and interleukin-6). Blood collection All blood samples were collected through antecubital venous puncture with a 21 gauge needle between 10:00 am and 1:00 pm. The four tests were performed within two hours of the collection. Definition of HPR The cut-off values used to define HPR were: PFA-100 ® , closure time (CT) < 150 seconds; 18 VFN, aspirin reaction units (ARU) ≥ 550 (according to the manufacturer); WBPA with AA, Ω ≥ 3; 19 WBPA with collagen, Ω ≥ 10. 20 Statistical analysis The sample size was calculated based on the expected mean result of the PFA-100 ® test, which was 191 seconds ± 100 21 during the acute phase, and the 25-second reduction estimate of that value in the chronic phase. According to the McNemar test, with 80% power and alpha of 0.05, 70 patients were required. The continuous variables were evaluated for their distribution (Gaussian or not) using the Kolmogorov-Smirnov test. Parametric continuous variables were presented as mean ± standard deviation, and nonparametric variables as medians and interquartile ranges (25-75). The unpaired Mann-Whitney (non-Gaussian variables) or Student’s T (Gaussian variables) tests were used with the Welch correction when indicated. When comparing two different moments, the Wilcoxon test was used for the non-Gaussian variables and the paired Student’s T for Gaussian samples. The categorical variables were presented in relative and absolute frequencies. Contingency distribution tables were analyzed using the chi-square test and Fisher’s exact test. Analysis of the correlation between the tests was done with Spearman's correlation coefficient. Values of p < 0.05 were considered statistically significant. The software used was SPSS (IBM Corporation), version 11. Results Patients’ characteristics The demographic and baseline characteristics of the patients are summarized in Table 1. Almost half of the patients reported a previous history of diabetes. The majority (64%) had a classification for thrombolysis in myocardial infarction (TIMI) with risk for non-ST segment elevation ACS equal to 3 or 4 on admission. All patients were on 100 to 200 mg ASA as the only antiplatelet agent in the last 7 days prior to the collection of the tests, both in the acute phase and in the late phase. Primary objective Platelet aggregation tests were divided into COX-1-specific (WBPA with AA and VFN) and COX-1-nonspecific (WBPA with collagen and PFA-100®). COX-1-specific tests were associated with higher platelet reactivity in the acute phase, compared to the late phase (Figure 1). Comparisons between the phases by the nonspecific COX-1 tests did not show 358