She was a cigarette smoker, with a history of diabetes, hypertension, hypercholestrolemia on statin therapy (atorvastatin), and with known coronary artery disease on aspirin. intracoronary stent implantation. Dual antiplatelet therapy C aspirin plus clopidogrel C is recommended for the reduction of acute and subacute stent thrombosis [1,2]. Despite combined antiplatelet therapy, stent thrombosis persists at a rate of 0.5C2% in elective instances, and up to 6% in individuals with acute coronary syndromes [3]. Stent thrombosis is definitely a life-threatening event [4]. In addition, also in instances of immediate reperfusion therapy by means of emergency PCI, individuals with stent thrombosis have developed a major myocardial infarction, with consequent significant decrease in remaining ventricular function C a strong bad predictor of long-term survival [3]. “Retrospective” laboratory testing in individuals with stent thrombosis has shown that poor response (“resistance”) to antiplatelet therapy is definitely a risk element for this event [5-7]. Case statement A 67-12 months old female was admitted to Cardiocentre for an elective coronary angiography, because of changes within the ECG (fresh bad T waves in prospects I, aVL, V1-V3) and fresh anteroapical hypokinesis seen by echocardiography. She was a cigarette smoker, with a history of diabetes, hypertension, hypercholestrolemia on statin therapy (atorvastatin), and with known coronary artery disease on aspirin. The patient fulfilled the inclusion criteria of the PRAGUE-8 trial (observe section methods) [8]. After signing of educated consent, she was randomized into group B of this study, and also participated in the vasodilator stimulated phosphoprotein (VASP) phosphorylation state and genetic laboratory substudies. In the laboratory substudy, the time course of platelet inhibition after clopidogrel (600 mg loading dose followed by 75 mg per day) was investigated. On the second day time of hospitalization, the patient underwent a coronary angiography, which showed an 80% stenotic lesion on her remaining anterior descending artery. The lesion AZD-5991 Racemate was treated with ad hoc performed PCI with the implantation of a bare metallic stent. The success of the procedure was ideal (Number 1A, B). The next day, the patient was stable, did not have any complications, and was discharged home. The recommendation for drug therapy was as follows: ASA (100 mg/d), clopidogrel (75 mg/d), metoprolol, ramipril, atorvastatin, peroral antidiabetic. Open in a separate window Number 1 Coronary angiography and pecutaneous coronary intevention studies. A, B C elective during the 1st hospitalization; C, D C urgent during the second hospitlization. 46 hours after stent implantation, the patient returned to the hospital because of chest pain, vertigo and swelling. There were ST section elevations in prospects V1-V3 and AZD-5991 Racemate a new second-degree A-V block according to the ECG (Number ?(Figure2).2). An emergency coronary angiography was performed, and showed 100% occlusion of the remaining anterior descending artery due to acute stent thrombosis. Immediate ballon angioplasty with heparin and eptifibatide opened the artery and led to a good angiographic result (Number 1C, D). Open in a separate window Number 2 ECG at the second hospital admission. What did the VASP phosphorylation study show? There was APO-1 no reaction to the administration of clopidogrel C the patient was completely “resistant” to this drug (Number ?(Figure3).3). Interestingly, AZD-5991 Racemate by the second admission the ADP-stimulated platelet reactivity was actually higher than the basal value without clopidogrel therapy. The most probable explanation for this was an acute myocardial infarction, which was the reason behind the second hospitalization. Open in a separate window Number 3 Clopidogrel effectiveness; ADP-induced platelet activation (Platelet reactivity index) [11]before and after clopidogrel. In the genetic substudy we investigated the prevalence of nine platelet and haemostatic gene polymorphisms. The results of this considerable genetic screening are demonstrated in Table ?Table1.1. Detected solitary nucleotid polymorphisms of P2Y12 and GPIIIa receptors had been recognized as possible intrinsic mechanisms of clopidogrel resistance [8,9]. Table 1 Genetic screening for platelet polymorphisms and procoagulation state thead PolymorphismResult /thead Leiden mutationNegative hr / Element II mutationNegative hr / P2Y12 H1/H2 haplotypNegative hr / P2Y12 (32C/T)Heterozygote hr / GPVI (13254C/T)Bad hr / PAR-1 (IVSn-14A/T)Heterozygote hr / GPIIIa (PlA1/PlA2)Heterozygote hr / COX-1 (-842A/G)Bad hr / COX-1 (50C/T)Bad Open in a separate window Methods em The PRAGUE-8 study /em was a randomized multi-center open label medical trial which compared the routine clopidogrel 600 mg pretreatment more than 6 hours before coronary angiography (group A) with the selective administration of clopidogrel 600 mg only for PCI individuals in the catheterization laboratory, after the coronary angiography and just prior to PCI (group B) (ClinicalTrials.gov identifier NCT00432120) [10]. The inclusion criteria were: a planned elective coronary angiography for suspected or verified chronic stable coronary artery disease or medically fully stabilized acute coronary syndrome, a signed written educated consent, and age 18 years. The primary.
