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 Table 1 – Demographic and baseline characteristics of patients Number of patients 70 Age, years (mean ± SD) 64.2 ± 9.7 Female, n (%) 38 (54.3) Medical history Diabetes mellitus, n (%) 34 (48.6) Hypertension, n (%) 61 (87.1) Dyslipidemia, n (%) 58 (82.9) Current smoking, n (%) 11 (15.7) Obesity, n (%) 16 (22.9) Family history of CAD, n (%) 28 (40) AMI, n (%) 41 (58.6) SMR or PCI, n (%) 38 (54.3) CHF, n (%) 6 (8.6) Type of ACS Unstable angina, n (%) 54 (77.1) NSTE AMI, n (%) 16 (22.9) TIMI risk score 0 to 2, n (%) 15 (21) 3 to 4, n (%) 45 (64) ≥ 5 (%) 10 (15) Previously used medications PPIs, n (%) 32 (45.7) Beta-blockers, n (%) 55 (78.6) Calcium channel blockers, n (%) 10 (15) ACEIs/ARBs, n (%) 45 (64.3) Aldosterone antagonists, n (%) 3 (4.3) Laboratory tests Median (25 th /75 th ) Hemoglobin, g/dL 13.7 (12.8/14.7) Leukocytes × 1.000/mm 3 8.0 (6.5/9.2) Platelets × 1.000/mm 3 220 (179/273) Creatinine, g/dL 1.0 (0.9/1.2) ARBs: angiotensin receptor blockers; SMR: Surgical myocardial revascularization; CAD: coronary artery disease; AMI: acute myocardial infarction; PPIs: proton pump inhibitors; CHF: congestive heart failure; PCI: percutaneous coronary intervention; ACEIs: angiotensin converting enzyme inhibitors; ACS: acute coronary syndrome; NSTE: non-ST segment elevation; TIMI: thrombolysis in myocardial infarction. significant differences (PFA = 215.9 ± 83.75 seconds versus 200.51 ± 84.63 seconds, respectively, in the acute and late phases, p = 0.233; WBPA with collagen, 7.19 ± 5.64 Ω versus 6.46 ± 5.09 Ω, p = 0.658). When the results were categorized according to pre‑established cutoff values for HPR diagnosis (Table 2), COX‑1‑specific tests were associated with significant differences between the acute and late phases (WBPA with AA, 31.4% versus 12.8%, p = 0.015; VFN, 32.1% versus 16%, p = 0.049), whereas nonspecific tests did not show significant differences (PFA, 34.2% versus 40%, p = 0.50; WBPA with collagen, 33.8% versus 30.8%, p = 0.86). Secondary objectives Correlation between platelet tests In the acute phase, the analyzed methods correlated significantly (Table 3). However, the magnitude of this correlation was only moderate (r > 0.4) between WBPA with AA and WBPA with collagen. The correlation between the other methods was only weak (r > 0.2 and < 0.4). Variation of inflammatory markers and platelet reactivity between acute and late phases C-reactive protein (CRP) levels differed significantly between the acute and late phases [median CRP = 2.84 mg/dL (1.54 to 8.41) versus 1.41 mg/dL (0.73 to 5.64), p = 0.006], whereas interleukin-6 (IL-6) did not differ between the two phases [median IL-6 = 2.1 pg/mL (2.0 a 5.68) versus 2.0 pg/mL (2.0 to 3.25), p = 0.110]. When CRP (acute/late) variation was compared to the variation of the methods in the two phases analyzed, a weak but significant correlation (Figure 2) was demonstrated between CRP and VFN (r = 0.29, p= 0.03). Discussion Our data demonstrate significant differences in response to ASA during the acute and late phases of acute coronary disease. Previous studies have unequivocally documented that ASA reduces the occurrence of cardiovascular events in patients with CAD. 4-7 Even with the advent of the new antiplatelet agents that act by blocking the P2Y12 receptor, the role of ASA remains unchanged as it is considered, in all guidelines, a routine treatment in this population. 1-2 However, it has been well established that there is significant variability in residual platelet function during ASA therapy, especially in the context of ACS, in which the prevalence of HPR is more evident. 8,17 The reason for this variability is not fully understood. One hypothesis is that HPR is present in a subpopulation of patients with chronic CAD, leading to a decrease in the efficacy of ASA and, as a consequence, increasing the likelihood of developing ischemic cardiovascular events. Another hypothesis is that HPR develops during the acute ischemic episode, as a consequence of the increase in platelet reactivity due to phenomena occurring in the acute phase (increased inflammatory activity, increased rate of platelet renewal, activation of the coagulation system, among others). To our knowledge, this study was the first to test both hypotheses in the same population of patients with NSTE ACS. Our results showed that, for most patients, HPR is labile, with a higher prevalence observed during the acute phase compared to the late phase. These results are consistent with the data reported by Hobikoglu et al., 21 who analyzed two different populations (one group of patients hospitalized with ACS and another group of patients with chronic CAD). The present demonstrations can have a significant therapeutic impact, since approximately one third of our patients showed HPR during the initial phase of ACS, and new regimens, including change of dosage and use of more potent antiplatelet agents, may be proposed to reduce the risk of ischemic events. Neubauer et al. 22 evaluated a therapeutic regimen of dose escalation of ASA and clopidogrel in 359