Pharmacokinetics and pharmacogenetics of edoxaban

Edoxaban is a new generation of oral anticoagulant; it is selective, direct and reversible inhibitor of activated blood coagulation factor X (F Xa), serine protease responsible for thrombin formation. Edoxaban is used to prevent stroke in non-valvular atrial fibrillation, to treat deep vein thrombosis and pulmonary embolism. The purpose of the review is to analyze the associative studies of OHB of CYP3A4 / 5 and ABCB1 genes, as well as to search for new candidate genes reflecting the efficacy and safety of edoxaban. The search for full-text publications in Russian and English over the past two decades was carried out in eLibrary, PubMed, Web of Science, OMIM databases using the following keywords: edoxaban, pharmacokinetics, pharmacogenetics, efficacy, and safety. The review covers pharmacokinetics of edoxaban, as well as pharmacogenetic features of the drug metabolism in details. Candidate genes influencing concentration of edoxaban are genes encoding key enzymes of its metabolism – CES1, CYP3A4 / 5, ABCB1, and, to a lesser extent, SLCO1B1. By present day, numerous NVS of candidate genes have been identified. They potentially affect pharmacokinetics of edoxaban, but their role in real clinical practice requires further study

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Pharmacokinetics and Pharmacogenetics of Apixaban

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2020-10-17 ◽

2020 ◽

Vol 16 (5) ◽

pp. 852-860

Author(s):

A. V. Savinova ◽

M. M. Petrova ◽

N. A. Shnayder ◽

E. N. Bochanova ◽

R. F. Nasyrova

Keyword(s):

Candidate Genes ◽

Factor Xa ◽

Potential Candidate ◽

Beta Oxidation ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Vein Thrombosis ◽

Genes Encoding ◽

Deep Vein

Apixaban is oral anticoagulant, it is widely used in prevention of stroke in non-valvular atrial fibrillation and treatment of deep vein thrombosis and pulmonary embolism. Its main mechanism of action is through reversible inhibition of factor Xa. It specifically binds and inhibits both free and bound factor Xa which ultimately results in reduction in the levels of thrombin formation. Apixaban is mainly metabolized by CYP3A4 with minor contributions from CYP1A2, CYP2C8, CYP2C9, CYP2C19 and CYP2J2 isoenzymes. Some of the major metabolic pathways of apixaban include o-demethylation, hydroxylation, and sulfation, with o-demethylapixabansulphate being the major metabolite. The aim of this review is analysis of associated researches of single nucleotide variants (SNV) of CYP3A5 and SULT1A1 genes and search for new candidate genes reflecting effectiveness and safety of apixaban. The search for full-text publications in Russian and English languages containing key words “apixaban”, “pharmacokinetics”, “effectiveness”, “safety” was carried out amongst literature of the past twenty years with the use of eLibrary, PubMed, Web of Science, OMIM data bases. Pharmacokinetics and pharmacogenetics of apixaban are considered in this review. The hypothesis about CYP и SULT1A enzymes influence on apixaban metabolism was examined. To date, numerous SNVs of the CYP3A5 and SULT1A1 genes have been identified, but their potential influence on pharmacokinetics apixaban in clinical practice needs to be further studies. The role of SNVs of other genes encoding beta-oxidation enzymes of apixaban (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2J2) and transporter proteins (ABCB1, ABCG2) in its efficacy and safety are not well understood, and ABCB1 and ABCG2 genes may be potential candidate genes for studies of the drug safety.

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Advances of Thrombectomy in Venous Thromboembolism

10.5772/intechopen.100044 ◽

2021 ◽

Author(s):

Jia-Ling Lin ◽

Po-Sheng Chen ◽

Po-Kai Yang ◽

Chih-Hsin Hsu

Keyword(s):

Venous Thromboembolism ◽

Oral Anticoagulants ◽

Current Evidence ◽

Efficacy And Safety ◽

Vein Thrombosis ◽

Surgical Thrombectomy ◽

New Generation ◽

Deep Vein

Venous thromboembolism (VTE) presenting as deep vein thrombosis and pulmonary embolism clinically is a potentially fatal cardiovascular diseases with short-term and long-term sequelae. Furthermore, there is high recurrent rate in VTE patients during follow-up. Anticoagulation with traditional anticoagulants or new generation of oral anticoagulants is the gold standard treatment in patients with VTE. On the other hand, there is remarkable progression in device-based or surgical thrombectomy in managements of VTE in recent years. Current evidence also demonstrates the efficacy and safety of these invasive procedures in selective VTE patients. The present article will illustrate recent advances of device-based or surgical thrombectomy in VTE treatment.

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Intensive Initial Oral Anticoagulation and Shorter Heparin Treatment in Deep Vein Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661195 ◽

1984 ◽

Vol 52 (03) ◽

pp. 276-280 ◽

Cited By ~ 17

Author(s):

Sam Schulman ◽

Dieter Lockner ◽

Kurt Bergström ◽

Margareta Blombäck

Keyword(s):

Deep Vein Thrombosis ◽

Oral Anticoagulation ◽

Dose Group ◽

Low Dose ◽

Clinical Signs ◽

Coagulation Factor ◽

High Dose ◽

Vein Thrombosis ◽

Heparin Treatment ◽

Deep Vein

SummaryIn order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective, we performed a prospective randomized study in patients with deep vein thrombosis. They received either the conventional regimen of oral anticoagulation (“low-dose”) and heparin or a more intense oral anticoagulation (“high-dose”) with a shorter period of heparin treatment.In the first part of the study 129 patients were randomized. The “low-dose” group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the “high-dose” group after 3.3 days. Heparin was discontinued after 6.0 and 5.0 days respectively. There was no difference in significant hemorrhage between the groups, and no clinical signs of progression of the thrombosis.In the second part of the study another 40 patients were randomized, followed with coagulation factor II, VII, IX and X and with repeated venograms. A stable therapeutic PT-level was achieved after 4.4 (“low-dose”) and 3.7 (“high-dose”) days, and heparin was discontinued after 5.4 and 4.4 days respectively. There were no clinical hemorrhages, the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred.Our oral anticoagulation regimen with heparin treatment for an average of 4.4-5 days seems safe and reduces in-patient costs.

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Examination of the Effectiveness of Direct Oral Anticoagulants in Comparison to Warfarin in an Obese Population

Journal of Pharmacy Technology ◽

10.1177/87551225211064113 ◽

2021 ◽

pp. 875512252110641

Author(s):

Rachel M. Watson ◽

Carmen B. Smith ◽

Erica F. Crannage ◽

Laura M. Challen

Keyword(s):

Primary Outcome ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Efficacy And Safety ◽

Class Iii ◽

Vein Thrombosis ◽

Class Iii Obesity ◽

Recurrent Vte ◽

The Individual ◽

Deep Vein

Background: While commonly prescribed today, direct oral anticoagulants (DOACs) have historically been avoided in patients with class III obesity or a weight >120 kg due to limited literature regarding the efficacy and safety in this population. Objective: The overall objective was to examine the effectiveness of DOACs compared to warfarin in a population with obesity. Methods: Patients with a diagnosis of venous thromboembolism (VTE) or atrial fibrillation and a body mass index (BMI) ≥35 kg/m2 from August 1, 2015, to August 1, 2020, were included in this retrospective cohort study. Patients receiving a DOAC were matched in a 1:2 ratio to warfarin. The primary outcome was a composite of stroke or recurrent VTE. Secondary outcomes included the individual components of the primary outcome, hospitalization for bleed, and the primary outcome in patients with a BMI ≥40 kg/m2. Results: A total of 162 patients were included, with 54 and 108 in the DOAC and warfarin groups, respectively. Baseline BMI was similar between groups (45.7 kg/m2 for DOACs vs 43.8 kg/m2 for warfarin), with approximately 70% of patients having a BMI ≥40 kg/m2. The primary outcome occurred in 1 patient (1.9%) in the DOAC group and 2 patients (1.9%) in the warfarin group. The DOAC group had a higher, nonsignificant incidence of bleeding (5.6% vs 0.9%, P = 0.11). There was no difference between groups in incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), or stroke in patients with a BMI ≥40 kg/m2. Conclusion: DOACs may be as efficacious as warfarin in the prevention of stroke or recurrent VTE in patients with a BMI of ≥35 kg/m2. Prospective, randomized trials are warranted to further assess the efficacy and safety of DOACs in this population.

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Direct Oral Anticoagulant Edoxaban in Patients with Non-Valvular Atrial Fibrillation: Results of Direct Comparison with Warfarin

Kardiologiia ◽

10.18087/cardio.2020.8.n1244 ◽

2020 ◽

Vol 60 (8) ◽

pp. 124-129

Author(s):

I. S. Yavelov

Keyword(s):

Atrial Fibrillation ◽

Coagulation Factor ◽

Vitamin K Antagonist ◽

Direct Oral Anticoagulant ◽

Factor X ◽

Efficacy And Safety ◽

Nonvalvular Atrial Fibrillation ◽

Double Blind ◽

Double Blind Placebo ◽

Controlled Clinical Study

This review analyzes results of a large prospective, randomized, double-blind, placebo-controlled clinical study ENGAGE AF-TIMI 48 that compared efficacy and safety of warfarin, a vitamin K antagonist, and edoxaban, an oral inhibitor of activated coagulation factor X. The review addresses important practical aspects of using edoxaban in patients with nonvalvular atrial fibrillation.

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Rivaroxaban in der Prävention und Therapie thromboembolischer Erkrankungen

Hämostaseologie ◽

10.5482/hamo-12-05-0005 ◽

2012 ◽

Vol 32 (03) ◽

pp. 195-202

Author(s):

T. Helbing ◽

C. Bode ◽

M. Moser

Keyword(s):

Low Dose ◽

Factor Xa ◽

Coagulation Factor ◽

Replacement Surgery ◽

Vein Thrombosis ◽

Hip Replacement Surgery ◽

Coronary Syndrome ◽

Prevention And Treatment ◽

Deep Vein ◽

Routine Coagulation

SummaryRivaroxaban (Xarelto®) is a new anticoagulant for the prevention and treatment of thromboembolic disorders. Rivaroxaban inhibits coagulation factor Xa directly, has high oral bioavailability, shows low propensity for drug-drug interactions and requires no routine coagulation monitoring. In patients undergoing elective knee or hip replacement surgery rivaroxaban (10 mg/d) is highly effective to prevent venous thromboembolism. In patients with non-valvular atrial fibrillation rivaroxaban (20 mg/d) has been approved to prevent stroke or systemic embolism. The favourable benefit-risk profile of rivaroxaban in the treatment of deep vein thrombosis (DVT) was shown in EINSTEIN-DVT and led to its clinical approval (twice daily 15 mg for 3 weeks, followed by 20mg/d). Based on ATLASACS-TIMI-51 which has shown that rivaroxaban (2.5 mg twice daily) reduced thrombotic cardiovascular events and mortality in patients with a recent acute coronary syndrome, the approval of low dose rivaroxaban has been submitted for this indication.Taken together, rivaroxaban may become an effective alternative to standard anticoagulants in the prevention and treatment of thromboembolic disorders.

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The Use of Low Molecular Weight Heparins for Post-Surgical Deep Vein Thrombosis Prevention in Orthopaedic Patients

Journal of International Medical Research ◽

10.1177/030006058801600505 ◽

1988 ◽

Vol 16 (5) ◽

pp. 359-366 ◽

Cited By ~ 13

Author(s):

E. Chiapuzzo ◽

G. B. Orengo ◽

G. Ottria ◽

A. Chiapuzzo ◽

E. Palazzini ◽

...

Keyword(s):

Molecular Weight ◽

Deep Vein Thrombosis ◽

Low Molecular Weight Heparin ◽

Control Group ◽

Low Molecular Weight ◽

Factor X ◽

Vein Thrombosis ◽

Orthopaedic Patients ◽

Antithrombotic Efficacy ◽

Deep Vein

The prophylactic antithrombotic efficacy of a low molecular weight heparin was compared with a traditional unfractionated calcium heparin after orthopaedic surgery in 140 patients. Deep vein thromboses were detected in legs either by Doppler sonography or [125I]fibrinogen uptake tests in five (7.1%) and seven (10%) patients, respectively. The capacity of both drugs to prevent deep vein thrombosis was demonstrated. Compared with the control group, those who used low molecular weight heparin showed a significant increase of activated factor X inhibition and smaller increases in activated partial thromboplastin times. Tolerability of both drugs was good, with a low incidence of local side-effects.

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A case-controlled study on AngioJet rheolytic thrombectomy and catheter-directed thrombolysis in the treatment of acute lower extremity deep venous thrombosis

Vascular ◽

10.1177/1708538119877322 ◽

2019 ◽

Vol 28 (2) ◽

pp. 177-182 ◽

Cited By ~ 2

Author(s):

Jun Zhu ◽

Cai-Fang Ni ◽

Zhen-Yu Dai ◽

Li-Zheng Yao ◽

Wen-Hui Li

Keyword(s):

Deep Vein Thrombosis ◽

Lower Extremity ◽

Controlled Study ◽

Efficacy And Safety ◽

Vein Thrombosis ◽

Catheter Directed Thrombolysis ◽

Rheolytic Thrombectomy ◽

Thrombus Removal ◽

The Mean ◽

Deep Vein

Objective This study aims to compare the efficacy and safety of AngioJet rheolytic thrombectomy vs. catheter-directed thrombolysis in patients with acute lower extremity deep vein thrombosis. Methods Between the period of February 2015 and October 2016, 65 patients with documented acute lower extremity deep vein thrombosis were treated with catheter-directed intervention. These patients were divided into two groups: AngioJet group and catheter-directed thrombolysis group. Comparisons were made with regard to efficacy and safety between these two groups. Results In the AngioJet group, complete or partial thrombus removal was accomplished in 23 (72%) and 3 (9%) patients, respectively. In the catheter-directed thrombolysis group, complete or partial thrombus removal was accomplished in 27 (82%) patients and 1 (3%) patient, respectively. In the AngioJet group, the perimeter difference between the suffered limb and healthy one declined from 5.1 ± 2.3 cm to 1.4 ± 1.2 cm ( P < 0.05). In the catheter-directed thrombolysis group, the perimeter difference declined from 4.7 ± 1.6 cm to 1.5 ± 0.9 cm ( P < 0.05). The mean urokinase dose was 0.264 ± 0.135 million units in the AngioJet group and 1.869 ± 0.528 million units in the catheter-directed thrombolysis group ( P < 0.05). The duration of thrombolysis was 4.2 ± 1.7 h in the AngioJet group and 73.6 ± 18.3 h in the catheter-directed thrombolysis group ( P < 0.05). The occurrence of complications in these two groups was 19% and 18%, respectively (not significant). Conclusion AngioJet rheolytic thrombectomy is a new, safe and effective approach for treating acute lower extremity deep vein thrombosis. When compared to catheter-directed thrombolysis, this treatment provides similar success with lower urokinase dosage and shorter duration of thrombolysis.

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