Direct oral anticoagulants: An update

Moreno, Ana Isabel Franco; Díaz, Rosa; Navarro, María José García

doi:10.1016/j.medcle.2018.07.005

Cited by 19 publications

(13 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Already in 2004, ximelagatran, a direct oral FIIa inhibitor, was developed but withdrawn from the market due to hepatotoxicity. Subsequently, the new class of DOAC (dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban), which selectively and reversibly inhibit FIIa or FXa in the common pathway of the coagulation cascade, was introduced in clinical practice in 2010, 2011, 2012, 2015, and 2017, respectively, and led to a revolution in anticoagulant therapy ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

“…Predictable pharmacokinetics, ease of use, and a wide therapeutic window are the most important advantages of DOAC, leading to a quick uptake in prescriptions and broad use in clinical practice ( 6 , 7 ). Today, DOAC are the most commonly used anticoagulants in the western world ( 8 , 9 ), and two DOAC rank among the top 10 best-selling drugs worldwide ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Factor XI Inhibitors for Prevention and Treatment of Venous Thromboembolism: A Review on the Rationale and Update on Current Evidence

Nopp

Kraemmer

2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Although anticoagulation therapy has evolved from non-specific drugs (i.e., heparins and vitamin K antagonists) to agents that directly target specific coagulation factors (i.e., direct oral anticoagulants, argatroban, fondaparinux), thrombosis remains a leading cause of death worldwide. Direct oral anticoagulants (i.e., factor IIa- and factor Xa-inhibitors) now dominate clinical practice because of their favorable pharmacological profile and ease of use, particularly in venous thromboembolism (VTE) treatment and stroke prevention in atrial fibrillation. However, despite having a better safety profile than vitamin K antagonists, their bleeding risk is not insignificant. This is true for all currently available anticoagulants, and a high bleeding risk is considered a contraindication to anticoagulation. As a result, ongoing research focuses on developing future anticoagulants with an improved safety profile. Several promising approaches to reduce the bleeding risk involve targeting the intrinsic (or contact activation) pathway of coagulation, with the ultimate goal of preventing thrombosis without impairing hemostasis. Based on epidemiological data on hereditary factor deficiencies and preclinical studies factor XI (FXI) emerged as the most promising candidate target. In this review, we highlight unmet clinical needs of anticoagulation therapy, outlay the rationale and evidence for inhibiting FXI, discuss FXI inhibitors in current clinical trials, conduct an exploratory meta-analysis on their efficacy and safety, and provide an outlook on the potential clinical application of these novel anticoagulants.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Factor XI Inhibitors for Prevention and Treatment of Venous Thromboembolism: A Review on the Rationale and Update on Current Evidence

Nopp

Kraemmer

2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…Warfarin helps prevent strokes in patients with AF and is the most important anticoagulant agent, but it also has many limitations including the need for frequent laboratory monitoring, unwanted drug and food interactions, slow onset of action, and a narrow therapeutic window (Lip and Agnelli, 2014). Thus, new direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban have been studied and manufactured to try to meet the needs of clinical anticoagulation without the shortcomings of warfarin (Thachil, 2014;Michalcová et al, 2016;Burn and Pirmohamed, 2018;Franco Moreno et al, 2018). DOACs act specifically on a single target (either thrombin or factor Xa) to inhibit clot formation and fibrin deposition (Lip and Agnelli, 2014).…”

Section: Introductionmentioning

confidence: 99%

Influence of ABCB1 Gene Polymorphism on Rivaroxaban Blood Concentration and Hemorrhagic Events in Patients With Atrial Fibrillation

Wang

Chen

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Background and Objectives: Genetic data on the pharmacokinetics of rivaroxaban and identification of factors that affect its biotransformation, distribution, and excretion will allow for generation of algorithms for personalized use of this drug in patients with atrial fibrillation (AF). Here we tested the effects of ABCB1 (ATP-binding cassette subfamily B member 1) polymorphisms on the valley rivaroxaban blood concentration and on the frequency of hemorrhagic events in patients with AF and propose a personal anticoagulation therapy management protocol.Patients and Methods: This is a retrospective study. We enrolled Mongolian descent patients who met the criteria from May 2018 to August 2019 in Beijing and Fujian. Clinical data on gender, height, weight, liver and kidney functions, drug trough concentration, and drug dosage were collected; we recorded the bleeding events until 6 months after initiating the medication. ABCB1 single nucleotide polymorphisms including rs1128503, rs1045642, and rs4148738 were identified. After reaching the steady state of plasma concentration, the peripheral blood was collected to detect the trough rivaroxaban plasma concentrations before the next medication.Results: We included 155 patients in this study including 81 men and 74 women, with an average age of 71.98 ± 10.72 years. The distribution of ABCB1 genotypes conformed to the Hardy–Weinberg equilibrium. Multiple comparisons between wild (TT) and mutant (CT and CC) genotypes at the rs1045642 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, p = 0.586; TT vs. CC, p = 0.802; and CT vs. CC, p = 0.702). Multiple comparison between wild (TT) and mutant (CC) genotypes at the rs1128503 locus revealed a significant difference of rivaroxaban trough concentrations (TT vs. CC, p = 0.0421). But wild (TT) vs mutant (CT) genotypes and mutant CT vs mutant CC genotypes at the rs1128503 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, p = 0.0651; TT vs. CT, p = 0.6127). Multiple comparisons between wild (GG) and mutant (AG and AA) genotypes at the rs4148738 locus showed no significant differences of rivaroxaban trough concentrations (GG vs. AG, p = 0.341; GG vs. AA, p = 0.612; AG vs. AA, p = 0.649). There was no significant correlation between ABCB1 gene variation loci rs1045642, rs1128503, rs4148738 and bleeding events.Conclusion: rs1128503 locus variations are correlated with the serum concentration of rivaroxaban in patients of Mongolian descent. But no significant correlation between rs1128503 locus variations and bleeding events were obtained.

show abstract

“…Venous thromboembolism (VTE) and atrial fibrillation (AF) have a prevalence of approximately 10 million cases annually and a reported 59.7 million cases in 2019 alone, respectively [ 1 , 2 ]. Warfarin therapy has proven its effectiveness in previous years in the prevention of such thromboembolic events [ 3 ]. In recent years, the emergence of direct oral anticoagulants (DOACs) has not only shown further efficacy but has overcome several limitations associated with warfarin use [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of direct oral anticoagulants in comparison with warfarin across different BMI ranges: A systematic review and meta-analysis

Almas¹,

Muhammad

Siddiqui

et al. 2022

Annals of Medicine &Amp; Surgery

View full text Add to dashboard Cite

Direct oral anticoagulants: An update

Cited by 19 publications

References 55 publications

Factor XI Inhibitors for Prevention and Treatment of Venous Thromboembolism: A Review on the Rationale and Update on Current Evidence

Factor XI Inhibitors for Prevention and Treatment of Venous Thromboembolism: A Review on the Rationale and Update on Current Evidence

Influence of ABCB1 Gene Polymorphism on Rivaroxaban Blood Concentration and Hemorrhagic Events in Patients With Atrial Fibrillation

Safety and efficacy of direct oral anticoagulants in comparison with warfarin across different BMI ranges: A systematic review and meta-analysis

Contact Info

Product

Resources

About