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Aim. To evaluate the clinical course and inhospital outcomes of myocardial infarction (MI) in patients receiving continuous direct oral anticoagulant (DOAC) therapy.Material and methods. Data from 390 patients treated for MI were included in the analysis. The mean age was 64.1±12.8 years. The majority were men (61,5%; n=240). All patients underwent standard diagnostic and therapeutic procedures according to clinical guidelines, including coronary angiography and percutaneous coronary intervention when indicated. Clinical, anamnestic and laboratory data (including C-reactive protein level, troponin I, coagulation test) were analysed. The inhospital course of MI, mortality and incidence of complications were evaluated.Results. Patients were divided into two groups according to DOAC therapy received. The main group included 41 patients with constant DOAC intake, while the control group consisted of 349 patients not receiving DOAC. Patients aged 65 years and older accounted for 68,3% (n=28) of the main group (p=0,0033), with a high proportion of cerebral circulation disorders and venous thrombosis (p0,05). Prior DOAC administration had no significant effect on the incidence of gastrointestinal bleeding (odds ratio (OR), 3,96 (95% Confidence Interval (CI) 0,76–20,66)) and mortality (OR 1,47 (95% CI 0,37-5,85)) during hospitalization.Conclusion. Patients with MI who received continuous DOAC therapy had significantly more frequent ST-segment resolution at hospital admission compared with patients who did not receive DOAC. DOAC administration had no significant effect on mortality and incidence of inhospital complications of MI.

Aim. To investigate the effect of ABCB1 gene carriage and interdrug interactions on apixaban pharmacokinetics and clinical outcomes in patients with atrial fibrillation and deep vein thrombosis.Material and methods. Patients hospitalized at Yudin State Clinical Hospital participated in the study. A total of 92 patients (50 patients received apixaban and 42 – rivaroxaban) with non-valvular atrial fibrillation and deep vein thrombosis were included. Genotyping was performed by real-time polymerase chain reaction. Direct oral anticoagulants concentrations were measured using an electrospray ionization mass spectrometer in positive ionization mode.Results. In our study we found that in patients carrying the CT+TT ABCB1 (rs4148738) C>T genotype encoding the carrier protein (P-gp), the plasma concentration of rivaroxaban was statistically significantly higher p= 0.026. In addition, we found that patients taking apixaban together with a CYP3A4/P-gp inhibitor were 3.5 times more likely to have hemorrhagic complications than those without inhibitors p = 0.004.Conclusion. Our study revealed that the plasma concentration of rivaroxaban was higher in patients carrying the ABCB1 (rs4148738) C>T polymorphism T allele. And patients taking apixaban together with CYP3A4/P-gp inhibitor had higher risk of hemorrhagic complications in comparison with patients not taking such drugs. Further studies are needed on the influence of pharmacogenetics and pharmacokinetics on the safety and efficacy profile of apixaban and rivaroxaban, taking into account the trend of systemic approach to optimization of anticoagulant therapy of direct oral anticoagulants based on pharmacokinetic, pharmacogenetic biomarkers.

Background: despite well-studied safety profile of dabigatran its interactions with genetic polymorphism parameters are poorly understood, especially in patients with moderate chronic kidney disease (CKD). This study was aimed to evaluate relationships between CES1 and ABCB1 polymorphism, dabigatran trough plasma concentration (DTPC) and bleeding events in patients with AF and CKD.Methods: patients with atrial fibrillation (AF) and stage 3 CKD treated with dabigatran 110mg or 150 mg have been included in the study. Real-time PCR was used to evaluate single nucleotide polymorphisms (SNPs) of the ABCB1 gene (rs1045642, rs4148738) and CES1 gene (rs2244613). A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index.Results: a total of 60 patients, aged 51–89 years (median age 76 years) were evaluated. Compared with patients given 150 mg twice a day, those given 110 mg twice a day were older (79 vs 67.5, p < 0.0001) and had lower creatinine clearance (CrCl) (50.5 vs 60.5 mL/min/1.73 m2, p = 0.015). We found C/D values to have high interindividual variability (mean 365.9 ± 290.4 μg/ml: mg/day, range 23.64-1452.73). Individuals with CKD 3B had higher concentration of dabigatran compared with those with 3A stage (488.7 ± 232.3 vs 332 ± 297.8 μg/ml : mg/day, p = 0.02). Consequently, there also was negative correlation of C/D with CrCl (r = -0.4, p = 0.0015). Evaluated SNPs (rs1045642, rs4148738, and rs2244613) did not affect C/D values (H test p > 0.05).Conclusions: C/D values were significantly higher in patients with CKD 3B stage and those treated with dabigatran 110 mg. There was no influence of aforementioned SNPs on dabigatran trough concentrations and clinical outcomes.

Since last few years a popularity of new oral anticoagulants significantly raised. There are following main direct oral anticoagulants (DOAC) used in therapy: Dabigatran, Rywaroxaban, Apixaban, Endoxaban. Dabigatran (Pradaxa) is the first oral direct thrombin inhibitor approved by FDA in stroke prevention in atrial fibrillation (AF). Anticoagulant effect occurs through direct thrombin binding. Unlike the vitamin K antagonists such as warfarin or acenokumarol, therapy with dabigatran has faster onset and offset action, doesn’t require routine monitoring has much less interactions. The main problem of treatment with dabigatran was difficulty in reversal of anticoagulant effect and overdose. Since three years the new antidote for dabigatran is available – Idarucizumab (Praxbind). Main indications for such use are dabigatran overdose, need of fast effect reversal before any interventions and life threatening bleeding. Despite other ways of anticoagulant effect reversal such as transfusion of plasma coagulation factors Idarucizumab is still highly recommended for direct use. Aim of this study is to review the new way of dabigatran reversal - Idarucizumab .