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Oral vitamin K antagonists (VKAs), warfarin, have been in routine clinical use for almost 70 years for various cardiovascular conditions. Direct-Acting Oral Anticoagulants (DOACs) have emerged as competitive alternatives for VKAs to prevent stroke in patients with non-valvular atrial fibrillation (AF) and have become the preferred choice in several...
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Context 1
... is an extremely potent factor Xa inhibitor with minimal renal clearance and minimal hepatic metabolism [40]. Betrixaban is the only FDA-approved DOACs for extended-duration prophylaxis for VTE in acute medically ill patients (Direct comparisons of betrixaban and the other direct oral anticoagulants can be found in Table 2) [41][42][43]. ...Similar publications
Introduction:
Lazertinib is an irreversible, mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Co-administration of TKIs with acid-reducing agents (ARAs) can lead to potential drug-drug interactions, which decreases solubility and absorption of TKIs and is ultimately associated with reduced efficacy of TKIs....
Citations
... Clinical trials have also shown that DOACs have similar or better efficacy and safety vs. warfarin [18]. Due to their increased convenience, efficacy, and safety, patients may be switched from warfarin to a DOAC in clinical practice settings [19]. ...
... International guidelines all now recommend DOACs instead of warfarin to prevent the risk of stroke/SE for patients with AF [28,29,32,33]. Consequently, NVAF patients who initiate warfarin can be switched to DOACs for legitimate clinical reasons [19]. However, different DOACs have varying efficacy and safety in patients with NVAF. ...
Introduction
There is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice.
Materials and methods
This study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB.
Results and conclusions
The final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39–0.96) and MB (HR: 0.67; 95% CI: 0.50–0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73–1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52–0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs.
... This approval is backed by significant findings from randomized controlled trials [7][8][9][10]. These DOACs offer several benefits, such as oral administration, fewer hemorrhagic complications, no requirement for constant lab monitoring, and improved patient adherence [11]. However, their availability is not as widespread as warfarin, and as newer arrivals, limited data are comparing their safety and effectiveness to warfarin [12]. ...
Introduction: Atrial fibrillation (AF) significantly heightens stroke risk, which can be mitigated through anticoagulation therapy. Although warfarin was traditionally employed for this purpose, the use of direct-acting oral anticoagulants (DOACs) is on the rise.
Methods: This retrospective study, which spanned from June 2016 to January 2018, focused on adult patients diagnosed with AF. Their treatments, either via warfarin or DOACs (apixaban, rivaroxaban, and dabigatran), were evaluated. Data analysis was done using Statistical Product and Service Solutions (SPSS, version 21; IBM SPSS Statistics for Windows, Armonk, NY). This study aims to evaluate the safety and effectiveness of DOACs versus warfarin in preventing thromboembolic complications among Saudi patients with AF.
Results: A total of 396 patients with AF, averaging 66 ± 14 years of age, were part of the study. Among them, there were slightly more female patients (205 or 51.8%). The majority of patients (223 or 56.3%) were treated with a DOAC, while the rest (173 or 43.7%) received warfarin. Furthermore, 93 patients (23.5%) were taking anti-platelet drugs. Statistically, the rate of ischemic stroke was significantly higher among patients treated with DOACs than with warfarin (p=0.005), but bleeding rates were similar in both groups. Specifically, the DOACs apixaban and rivaroxaban showed a significant association with the occurrence of stroke when compared to warfarin (p=0.012 and p=007, respectively).
Conclusion: Overall, both DOACs and warfarin presented similar results regarding hemorrhagic complications when treating AF patients. However, the DOACs apixaban and rivaroxaban displayed higher risks of ischemic stroke compared to warfarin.
... Nonvalvular atrial fibrillation (NVAF) is the most common indication for DOACs in international guidelines. 16 Several meta-analyses and clinical trials favored DOACs over VKAs for preventing systemic thromboembolic events or stroke in NVAF patients due to their more tolerable safety profile. 17,18 The international guidelines recommend DOACs over VKAs for a myriad of conditions, including NVAF, deep vein thrombosis and pulmonary embolism (PE), acute coronary syndrome, and patients undergoing hip or knee arthroplasty 3,19,20 (see Table 1). ...
The indications of direct oral anticoagulants (DOACs) have expanded over the past 15 years. DOACs are effective and safe oral anticoagulants associated with lower bleeding risks and mortality than vitamin K antagonists. However, DOAC users are prone to a considerable bleeding risk, which can occur at critical sites or lead to severe life-threatening conditions. Recent statistics indicated that major bleeding occurs in up to 6.62 DOAC users per 100 treatment years. With the increased use of DOACs in clinical practice, DOAC-associated major bleeding is expected to be encountered more frequently in the emergency department. The current international guidelines recommend specific reversal agents for the management of DOAC users with severe bleeding to reverse the anticoagulant effect and restore normal hemostasis. An individualized assessment was incorporated in specific clinical situations to guide the decision pathway of major bleeding management. However, specific reversal agents are unavailable or have limited availability in many countries, which is expected to negatively impact the clinical outcomes of DOAC-associated major bleeding. Limited real-world evidence is available from these countries regarding the clinical outcomes of patients with DOAC-associated major bleeding. This narrative review provided an updated assessment of the evidence-based approaches for the management of major bleeding in DOAC users. We also explored the clinical outcomes of patients with major bleeding from clinical settings where specific reversal agents are unavailable.
... Warfarin has a narrow therapeutic index, wide variability in efficacy between individuals, and can interact with other drugs (Mar et al., 2022). It acts by inhibiting vitamin K epoxide reductase (VKOR) and disruption of the synthesis of biologically active forms of vitamin K-dependent (VKD) clotting factors (FII, FVII, FIX, FX), as well as regulatory factors (protein C, protein S) Abdelnabi et al., 2022). Thus, warfarin is employed commonly for the prevention and treatment of the coagulopathic and thromboembolic disorders associated with cardiac valvereplacement, atrial fibrillation, and other cardiovascular conditions (Zhang et al., 2021). ...
Introduction: In clinical practice, warfarin is often combined with Compound Danshen dripping pill (CDDP) for the treatment of cardiovascular diseases. However, warfarin has a narrow therapeutic index, wide interindividual variability (genetic and non-genetic factors), and is susceptible to drug-drug interactions. Our previous study indicated that CDDP might interact with warfarin in individuals with the epoxide hydrolase gene (EPHX1; single-nucleotide polymorphism: rs2292566) A/A subtype. We sought to clarify the interaction between CDDP and warfarin associated with EPHX1 in a comprehensive and accurate manner.
Methods: Here, EPHX1 A and EPHX1 G cell lines were established. Expression of microsomal epoxide hydrolase (mEH), vitamin K epoxide reductase (VKOR), and vitamin K-dependent clotting factors (FII, FVII, FIX, FX) was measured by western blotting upon incubation with CDDP and warfarin. mEH activity was evaluated by measuring the transformation of epoxyeicosatrienoic acids into dihydroxyeicosatrienoic acids. Then, healthy volunteers (HVs) with the EPHX1 A/A genotype were recruited and administered warfarin and CDDP to investigate the pharmacokinetics and pharmacodynamics of warfarin.
Results: CDDP combined with warfarin could decrease expression of mEH and VKOR, and increase protein expression of FII, FVII, FIX, and FX, in EPHX1 A cells. CDDP could slightly influence the pharmacokinetics/pharmacodynamics of warfarin in HVs with the EPHX1 A/A genotype.
Discussion: Rational combination of CDDP and warfarin was safe with no risk of bleeding, but the therapeutic management is also needed. The clinical study is posted in the China Clinical Trial Registry (ChiCTR190002434).
... Extensive preclinical and clinical trial data have demonstrated that DOACs offer several advantages over traditional anticoagulants, such as warfarin, including predictable pharmacokinetics, rapid onset of action, and fewer drug-drug interactions [2,3]. DOACs have been shown to be effective in preventing and treating venous thromboembolism, as well as reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation [4,5]. In addition, DOACs have been found to be safe and well-tolerated, with a lower incidence of major bleeding events compared to traditional anticoagulants. ...
A small natural substance called cirsilineol (CSL), which was discovered in the plant Artemisia vestita, is lethal to many cancer cells and has antioxidant, anticancer, and antibacterial properties. Here, we investigated the underlying mechanisms of the antithrombotic action of CSL. We demonstrated that CSL has antithrombotic efficacy comparable to rivaroxaban, a direct blood coagulation factor Xa (FXa) inhibitor employed as a positive control, in inhibiting the enzymatic activity of FXa and the platelet aggregation induced by adenosine diphosphate (ADP) and U46619, a thromboxane A2 analog. The expression of P-selectin, the phosphorylation of myristoylated alanine-rich C kinase substrate by U46619 or ADP, and the activation of PAC-1 in platelets were inhibited by CSL. Nitric oxide production was increased by CSL in ADP- or U46619-treated human umbilical vein endothelial cells (HUVECs), although excessive endothelin-1 secretion was suppressed. CSL demonstrated strong anticoagulant and antithrombotic effects in a mouse model of arterial and pulmonary thrombosis. Our findings suggest that CSL is a potential pharmacological candidate for a novel class of anti-FXa and antiplatelet medications.
