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 clopidogrel resistance and the relationship of low response to dual antiplatelet therapy with major adverse cardiovascular events (MACE) was assessed in young ST-segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (PCI). Thus, we aimed to measure the prevalence of dual antiplatelet resistance in younger MI patients and to evaluate the effects of such poor response on their medical condition. Methods Patient population In this prospective observational study, 123 consecutive patients (< 45 years old), who were admitted to a large‑volume center with a diagnosis of STEMI and underwent primary PCI were included in the study. The exclusion criteria were: previous treatment with glycoprotein IIb/IIIa inhibitors, anticoagulant or non-steroid anti-inflammatory drugs in the last ten days, active malignancy, chronic inflammatory conditions, hemorrhagic diathesis, thrombolytic treatment within the last month, severe renal or liver disease and platelet counts < 100,000/mL, hematocrit count < 30% and no indication or unsuccessful of PCI. STEMI patients were defined as patients with typical chest pain at rest lasting more than 30 minutes, and ST-segment elevation ≥ 0.2 mV in 2 or more contiguous, precordial leads or adjacent limb leads on the standard 12-lead electrocardiogram (ECG). All primary PCI procedures were performed by operators who performmore than 100 PCIs/year at a single center (> 3000 PCIs/year). The minimum number of patients needed to be included for an effect size of 0.4 and 80% power was 156 for independent samples t-test and Mann-Whitney U test. During the follow-up 33 patients were excluded from the study due to suspected use of medications and finally, 123 patients were included in the study. The power for the final sample size was calculated at 70%. Sample size was calculated using the G-Power 3.9.1.2 package program and was also valid for other statistical tests used in the study. Initially, patients would be allocated into 2 groups – patients with drug resistance (n = 59) and drug responders (n = 64). However, to in order to make randomization between the groups more precise, 4 groups were formed according to the response to the drugs combined or alone. The study complied with the Declaration of Helsinki. Written informed consent was obtained from all patients who participated in the study and the study protocol was approved by the ethics committee of our university. Analysis of patient data Patients’ demographic data, past medical history, and previous medical therapies were collected. Risk factors were categorized as having or not having STEMI. Twelve‑lead ECGwas recorded for each patient immediately after hospital admission and the MI type was defined from the ECG. At 24–72 h after revascularization, a transthoracic echocardiography (Vivid S5 probe 3 S-RS/GE Healthcare, Wauwatosa, Wisconsin, USA) was performed to calculate left ventricular ejection fraction (LVEF) by using the biplane Simpson method. 8 Primary angioplasty was performed only for infarct-related artery (IRA) occlusion (either total or partial). Intervention success was defined as reduction of IRA obstruction or stenosis to 30%, with TIMI 3 flow just after coronary intervention. Study design In this prospective observational study, we followed a 2x2 factorial design to create groups according to the presence of aspirin and clopidogrel resistance; poor responders to aspirin (n = 20, 39.7 ± 3.7 years old), poor responders to clopidogrel (n = 23, 39.6 ± 4.1 years old), dual poor responders (n = 16, 40.5 ± 4.1 years old), dual responders (n = 64, 38.7 ± 4.0 years old). All patients received dual antiplatelet therapy for 1 year after discharge. After one year, aspirin was prescribed with cardiac therapy. Patients were called for control at the first month after the procedure, and every six months thereafter, and the compliance was checked. Patients who did not use antiplatelet therapy in the follow-up period were excluded from the study. At the end of three years, patients were asked about the occurrence of cardiovascular events and the relationship between these events and the response to antiplatelet agents was evaluated. Evaluation of antiplatelet resistance All participants received a chewable 300mg or 100mg aspirin (according to previous usage) and clopidogrel (600 mg loading dosage) before coronary angiography. Heparin (100 IU/kg) was administered after the decision to perform coronary intervention. After angioplasty, all patients were admitted to the coronary care unit, where routine antithrombotic therapy was given as daily dose 100 mg of aspirin, 75 mg of clopidogrel and subcutaneous administration of enoxaparin. The timing of platelet aggregation tests to identify hyporesponsiveness is also important. Thus, a screening procedure to determine aspirin and clopidogrel responsiveness was performed on the fifth day of admission to facilitate the steady state of drugs to be sure that platelet aggregation test was performed when maximal inhibition had been achieved. Whole blood aggregation was carried out with an impedance aggregometer, a Multiplate® platelet function analyser that operates on the surface of activated platelets to activate receptors that allow them to bind to artificial surfaces (Multiplate®; Dynabarte GmbH, Munich, Germany). Platelet aggregation was quantified as area under the curve, aggregation degree, and aggregation velocity. Platelet aggregation results were presented as aggregation unit (AU) ×min, and values over 500 AU × min were defined as resistance to antiplatelet agents (used in combination or separately). 9 Follow-up Patients’ data during follow-up were obtained from hospital records or by interviewing (in person or by telephone) the patients, their families, or their physicians. Primary clinical outcomes were composed of cardiovascular (CV) mortality, target vessel revascularization (TVR), non-fatal reinfarction, advanced heart failure and stroke. Secondary clinical outcomes were CV mortality, TVR, non-fatal reinfarction, stroke and advanced heart failure one by one. 139