No abstract

Background. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel administered to treat patients with acute coronary syndrome (ACS) is still being used. However, despite the proven efficacy of this treatment regimen, thromboembolic complications have been observed in some individuals. The reason for this phenomenon is linked to the so-called increased responsiveness of platelets despite high platelet resistance (HPR). A significant role in HPR is attributed to genetically determined differences in the absorption and activation of clopidogrel. Objectives. The aim of the study was to assess the incidence of polymorphisms of the ABCB1 and CYPC19 genes that encode proteins involved in the absorption and metabolism of clopidogrel. Material and methods. The analysis was performed in 199 consecutive patients from Lower Silesian voivodeship (Poland) who underwent coronary angioplasty with stenting for ACS. The single nucleotide polymorphism of the CYP2C19 and ABCB1 genes was performed using a mini sequencing or restriction fragment length polymorphism method. Results. The results of this study revealed the high incidence of patients who may be unresponsive to antiplatelet treatment due to genetic causes. The CYPC19*2 allele in the form of homozygote or mutation heterozygote appeared in 26. 1% of the study population. ABCB1 (C3435C> T) polymorphism was associated with 84% of patients. The total incidence of allelic disorders of low drug absorption and metabolism reached 14.6%. Conclusions. The data obtained should prompt clinicians to use more recent antiplatelet agents (ticagrelor or prasugrel) first, instead of clopidogrel.

Introduction: Although ticagrelor and prasugrel remain the standard antiplatelet treatments in acute coronary syndrome (ACS), numerous patients still present with indications for clopidogrel use.Aim: We aimed to assess the levels of clopidogrel active metabolite and to evaluate the effect of the drug on platelet inhibition in patients with ACS as compared with those with stable coronary disease. Patients were assessed for the presence of the most common genetic polymorphisms that reduce the absorption (ABCB1) and activation (CYP2C19*2 and CYP2C19*3) of clopidogrel to exclude the effect of genetic variability on drug concentrations and activity.Material and methods: This single-center, open-label, prospective study included 199 patients hospitalized due to ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) in Killip class I-III, who underwent percutaneous coronary intervention. The control group included 22 patients with stable coronary artery disease.Results: The mean (SD) levels of active clopidogrel were 17.1 (12.3) ng/ml in controls and 16.4 (12.0) ng/ml in the whole study group (p < 0.68). No differences were noted in clopidogrel levels between patients with STEMI and NSTEMI (mean (SD), 17.6 (2.3) ng/ml and 15.1 (11.5) ng/ml; p < 0.45) or between STEMI and NSTEMI groups and controls (p < 0.38 and p < 0.61, respectively). No effect of ABCB1 or CYP2C19 polymorphism was observed in the study subgroups.Conclusions: We concluded that ACS does not affect the levels of clopidogrel active metabolite or platelet inhibition in patients in Killip class I-III with or without CYP2C19 or ABCB1 gene polymorphisms.

W czasie wojny obronnej we wrześniu 1939 roku Uniejów i jego okolice były miejscem zaciętych walk pomiędzy oddziałami polskiej armii „Poznań” i niemieckiej 8 armii. Taktyczne znaczenie Uniejowa związane było ze znajdującą się tutaj przeprawą mostową, której utrzymanie miało kluczowe znaczenie dla wojsk polskich, maszerujących znad granicy w kierunku Warszawy. Pierwsza faza walk miała miejsce w dniach 6–7 września, gdy polski 60 pp z 25 DP uniemożliwił oddziałom 30 DP z 8 armii zdobycie i zniszczenie mostu w Uniejowie, a tym samym zapewnił bezpieczeństwo przeprawy oddziałom macierzystej armii. Uniejów był miejscem starcia wrogich sobie sił także nocą i rankiem 10 września. Oddziały kawalerii, podporządkowane armii „Poznań” i osłaniające rozpoczynającą się polską ofensywę (bitwa nad Bzurą), pod Uniejowem powstrzymały idące z odsieczą pod Łęczycę dalsze oddziały Wehrmachtu. Ułani 6 puł pokonali znajdujący się w Uniejowie oddział rozpoznawczy niemieckiej 221 DP. Intensywne walki w rejonie Uniejowa przyniosły znaczne straty wśród ludności cywilnej, zarówno mieszkańców miasta i okolicznych wsi, jak i uciekinierów w zachodnich części Polski. Niemieccy żołnierze dokonali kilku zbrodni wojennych. Autor zidentyfikował oddziały Wehrmachtu, odpowiedzialne za dokonane zbrodnie.

Background. Ticagrelor and prasugrel are widely used as antiplatelet therapy after coronary angioplasty. However, there is a group of patients with indications for clopidogrel treatment. This population includes patients with chronic or acute coronary syndrome who are treated invasively and have contraindications to the use of novel antiplatelet drugs due to antithrombotic treatment (particularly with non-vitamin K antagonist oral anticoagulants). A wide range of generic forms of clopidogrel are available on the market. However, it is unclear whether they are as effective as the originator drug.Objectives. In the current study, we aimed to assess the concentrations of the active metabolite of clopidogrel and its effect on platelet aggregation inhibition in patients receiving the originator drug in comparison with those receiving generic clopidogrel.Materials and methods. We enrolled 22 healthy individuals without polymorphisms in the ABCB1 gene and the allele variants CYPC19*2 and CYPC19*3. All participants received a loading dose of clopidogrel (600 mg), followed by a maintenance dose of 75 mg for the next 3 days. On day 3, blood samples were obtained 1 h after drug administration to assess active metabolite concentrations using liquid chromatography with tandem mass spectrometry. In each participant, platelet aggregation was assessed with light transmission aggregometry after 5-µmol/L and 10-µmol/L adenosine diphosphate (ADP) stimulation. Assays were performed for the originator clopidogrel and 2 different generic groups.Results. The mean ± standard deviation (SD) concentrations of active clopidogrel did not differ between the originator drug and 2 generic products with clopidogrel (12.7 ±5 pg/µL compared to 13.0 ±4 pg/µL compared to 14.4 ±4 pg/µL). Platelet aggregation inhibition after stimulation with 5 µmol/L and 10 µmol/L ADP was similar for all preparations.Conclusions. In comparison with original clopidogrel, the use of its generic form does not affect the blood concentrations of the active metabolite or its antiplatelet effect.