ABC | Volume 112, Nº2, February 2019

Original Article Somuncu et al Antiplatelet resistance in young MI patients Arq Bras Cardiol. 2019; 112(2):138-146 There are also studies showing that platelet function tests do not have a prognostic significance in contrast to our results. Reny et al. 17 detected that neither specific nor aggregation‑based assays of antiplatelet drug responsiveness have additional predictive contribution to the recurrence of ischemic events in stable cardiovascular patients. 17 But in this study, patients who had acute ischemic events less than one month before inclusion were excluded from the study. Consequently, poor antiplatelet drug response may be less critical in a stable cardiovascular patient because of less endothelial thrombogenicity and less platelet activation in the stable patients shown in previous studies. 18-20 It may be assumed that platelet function tests may havemore impact on clinical outcomes in our study group when considering that platelet activation is related to inflammatory processes, and that inflammation is one of the most important factors in acute coronary syndromes, especially in young STEMI patients. This study supports the view that standardized maintenance doses of antiplatelet drugs would not prevent MACE in some of the patients. Could it be possible to overcome platelet resistance by increasing the dose of medicine in our patient group? In some trials, increasing the dose of aspirin has allowed some reduction in aspirin resistance rates, but such effect is absent in 5-10% of patients. In addition, gastrointestinal hemorrhage and other side effects may increase when aspirin dose is increased in these patients. In addition, high doses of Aspirin can reduce the production of prostacyclin, an important endogenous vasodilator and antiplatelet agent, by inhibiting cyclooxygenase 2. Also, in our study, patients with only aspirin resistance did not differ in terms of MACE compared with patients with response to dual therapy, whereas patients with only clopidogrel resistance showed a significant difference. Geisler and colleagues have also shown that the response to clopidogrel may be reduced after acute coronary syndrome. 21 This suggests that high platelet activity following acute coronary syndrome may be present and the standard dose of clopidogrel may not be sufficient to inhibit platelets. In parallel to this, it was found that administration of a 600 mg loading dose of clopidogrel in patients already chronically treated with clopidogrel provide additional inhibition of ADP-induced platelet aggregation. 22 This information may be reflected in clinical practice, especially in some risky situations. Thus, in cases of inadequate response to clopidogrel, dose escalation or more potent inhibitors (ticagrelor, prasugrel) may be considered. For these reasons, whether high dose of aspirin or clopidogrel is beneficial to young MI patients with antiplatelet resistance is open to investigation. There are some limitations in our study. First, this was a single-center study whichmay result in selection bias. Moreover, since we studied a specific population, the number of patients participating in the study was relatively small. This may have prevented the difference between some groups from reaching statistical significance. Second, antiplatelet sensitivity was only measured once, and some researchers have suggested that it should be measured more than once. Furthermore, when heterogeneous results of different studies are considered, the use of a single laboratory method constitutes one important limitation of the study. However, the multiple platelet function test reduces the risk of laboratory errors because it is faster, less troublesome, and does not require specific preparation than conventional optical aggregometry. Third, because of the study design, results of platelet sensitivity test cannot be generalized to different age groups with other forms of coronary artery disease. Fourth, clopidogrel was used as the second antiplatelet agent for STEMI, as the use of other P2Y12 inhibitors had not been included in the guidelines during the study period. Therefore, we do not know whether the use of more potent P2Y12 inhibitors would be associated with a lower prevalence of poor aspirin responders. Finally, aspirin and clopidogrel serum levels were not measured. However, the medical history of each patient was taken by one-to-one interview, and patients with irregular drug usage were excluded from the study. Conclusion Although there are many studies in the literature on platelet response to different antiplatelet medications, many questions remain unanswered. In summary, we found that poor responsiveness to dual therapy is an essential predictor of MACE, including CV mortality and TVR in a three-year follow‑up period in young patients undergoing primary PCI for STEMI. Although more potent P2Y12 inhibitors have been shown to be useful after acute coronary syndrome according to guidelines, there is no clear study of their use after one year. Therefore, aspirin or clopidogrel should be used in the long term after acute coronary syndrome, particularly in young MI patients, who may be more likely to antiplatelet resistance in long-term. For this reason, although routine testing for antiplatelet resistance is not recommended in the general population, it should be considered for young MI patients and, if resistance is detected, more potent antiplatelet therapy may be used one year after acute coronary syndrome. More comprehensive investigations are required to clarify this. Author contributions Conception and design of the research: Somuncu MU, Demir AR, Karabag T; acquisition of data: Somuncu MU, Demir AR, Karakurt ST, Karakurt H; analysis and interpretation of the data: Somuncu MU, Karakurt ST, Karakurt H; statistical analysis: Karabag T; writing of the manuscript: Somuncu MU, Demir AR, Karakurt ST; critical revision of the manuscript for intellectual contente: Somuncu MU, Karakurt H, Karabag T. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding There were no external funding sources for this study. Study Association This study is not associatedwith any thesis or dissertationwork. 144