Direct Oral Anticoagulant Agents Research Articles

Risk of Haemorrhage Associated with Direct Oral Anticoagulation Versus Anti-platelet Therapy: A Systematic Review and Meta-Analysis

Abstract Background Among patients with atrial fibrillation, clinicians often prescribe anti-platelet therapy rather than oral anticoagulation which may relate to a concern that direct oral anticoagulants (DOAC) are associated with a higher risk of bleeding. We completed a meta-analysis to determine whether DOAC therapy, compared to single anti-platelet, was associated with an increased risk of major haemorrhage, with a primary focus on intracranial haemorrhage (ICH). Methods We searched PubMed and Embase databases up to 7/2/2024. Randomised controlled trials (RCT) that compared DOAC therapy to single anti-platelet agents were included. Trials with follow-up less than 30 days, or sample size less than 200 were excluded. A random-effects meta-analysis model was used to report pooled treatment effects and 95% confidence intervals (CIs). The primary outcome was occurrence of ICH. Results A total of 9 RCTs were included (n=45,493). Overall, DOAC therapy was not associated with significantly higher odds of ICH compared to anti-platelet therapy (Odds ratio (OR) 1.14; 95% CI, 0.71-1.82), but there was heterogeneity among trials (I2 = 49.3). In an analysis by DOAC agent, the respective estimates for ICH risk were; Rivaroxaban (OR 2.05; 95% CI, 1.09-3.83); Dabigatran (OR 1.00; 95% CI, 0.61-1.64) and Apixaban OR 0.72; 95% CI, 0.44-1.17). DOAC therapy was associated with higher odds of major haemorrhage compared to aspirin (OR 1.39; 95% CI,1.07-1.80), with the following estimates by agent; Rivaroxaban (OR 1.91; 95% CI 1.22-3.00); Dabigatran (OR 1.21; 95% CI 0.86-1.69); Apixaban OR 1.09; 95% CI 0.73, 1.63). DOAC therapy was associated with higher odds of GI haemorrhage then control (OR 1.39; 95% CI,1.11, 1.73). Conclusion DOAC therapy was not associated with a significantly higher risk of ICH compared to anti-platelet therapy, but risks may differ among DOAC agents. DOAC therapy was associated with a higher risk of major haemorrhage, mostly related to GI haemorrhage.

Challenges in laboratory testing of patients suspected of antiphospholipid syndrome: practical implications for clinicians.

This paper focuses on the laboratory tests necessary for the diagnosis of antiphospholipid syndrome (APS). Diagnosis starts with the selection of patients suspicious of having APS. The timing related to the clinical event is important to avoid false classification of APS patients. For the interpretation of the test results of antiphospholipid antibodies (aPL) understanding of all pitfalls and interferences is necessary. Lupus anticoagulant (LA) measurement remains a complex procedure with many pitfalls and interferences. The effect of anticoagulant therapy, the main confounder of LA measurement, can be overcome by removal agents for direct oral anticoagulants (DOAC) or by considering assays as Taipan snake venom time / Ecarin clotting time not affected by antivitamin K therapy and anti-Xa DOAC. However, both procedures have limitations. Solid-phase assays for anticardiolipin antibodies (aCL) and anti-β2-glycoprotein 1 antibodies (aβ2GPI) show inter-assay differences. Diagnosis is based on the measurement of three groups of aPL: LA, aCL and aβ2GPI, of IgG and IgM isotype. This allows to make antibody profiles that helps in identifying patients at risk. Other aPL, such as antibodies against the domain I of β2GPI and anti-phosphatidylserine-prothrombin antibodies may be useful in risk stratification of APS patients and in some specific situations of patients with incomplete antibody profile, but are not needed for diagnosis. Laboratory diagnosis of APS remains challenging. To increase the diagnostic efficacy and reliability, an integrated interpretation of all results and an interpretative comment should be provided on the laboratory report. Therefore, a close interaction between clinical pathologists and clinicians is mandatory.

Development of a Medication-Use Evaluation Template for Andexanet Alfa in the Reversal of Anticoagulation With Factor Xa Inhibitors.

Medication-use evaluations are meant to ensure that medication-use processes are consistent with prevailing standards of care, assure optimal use of therapy, and reduce the risk of medication-related problems. Reversal agents for direct oral anticoagulants are a worthy focus for medication-use evaluations for reasons of efficacy, safety, and cost. A multidisciplinary team of experts developed 2 medication-use evaluation templates illustrating the application of professional society guidelines to the appropriate use of andexanet alfa.

Non–Vitamin K Antagonist Versus Vitamin K Antagonist Oral Anticoagulant Agents After Transcatheter Aortic Valve Replacement

BackgroundStudies comparing long-term outcomes between non–vitamin K antagonist (VKA) oral anticoagulant agents (direct oral anticoagulant agents [DOACs]) and VKA anticoagulant agents after transcatheter aortic valve replacement (TAVR) are scarce, with conflicting results. ObjectivesThe aim of this study was to examine the periprocedural, short-term, and long-term safety and effectiveness of DOACs vs VKAs in patients undergoing TAVR via femoral access with concomitant indications for oral anticoagulation. MethodsConsecutive patients undergoing transfemoral TAVR in the prospective national SwissTAVI Registry between February 2011 and June 2021 were analyzed. Net clinical benefit (a composite of all-cause mortality, myocardial infarction, stroke, and life-threatening or major bleeding) and the primary safety endpoint (a composite of life-threatening and major bleeding) were compared between the VKA and DOAC groups at 30 days, 1 year, and 5 years after TAVR. ResultsAfter 1:1 propensity score matching, 1,454 patients were available for analysis in each group. There was no significant difference in the rate of the net clinical benefit and the safety endpoints between the groups as assessed at 30 days and 1 and 5 years post-TAVR between VKAs and DOACs. VKAs were associated with significantly higher rates of 1- year (HR: 1.28; 95% CI: 1.01-1.62) and 5-year (HR: 1.25; 95% CI: 1.11-1.40) all-cause mortality. Long-term risk for disabling stroke was significantly lower in the VKA group after excluding periprocedural events (HR: 0.64; 95% CI: 0.46-0.90). ConclusionsAt 5 years after TAVR, VKAs are associated with a higher risk for all-cause mortality, a lower risk for disabling stroke, and a similar rate of life-threatening or major bleeding compared with DOACs. (SwissTAVI Registry; NCT01368250)

Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Low Body Weight Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

Direct oral anticoagulant (DOAC) agents are established as the anticoagulation strategy of choice for a variety of clinical risks. Despite this, uncertainty still exists with regard to their efficacy and safety for the prevention of stroke and systemic embolism in some patient populations; most notably those with low body weight (LBW) (<60 kg or body mass index [BMI] <18 kg/m2). Currently, there is a paucity of trial and non-trial data to support a prescriptive recommendation for their use in these patient cohorts. We have carried out a pooled systematic review of the most up to date published data of patients stabilized on various DOAC analogs with the view to ascertaining the exact matrices of their efficacy and safety in these cohorts of patients. We initially carried out a comprehensive search of databases from inception to June 2023 for eligible studies exploring the efficacy and safety of various analogs of direct oral anticoagulants in patients with atrial fibrillation who had low body weight. Databases accessed include PubMed, EMBASE, the Science Citation Index, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness. We carried out a weighted comparison of derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes between various DOACs using the random effects model. Thirteen studies (n = 165,205 patients) were included in our meta-analysis. DOAC analogs were associated with increased stroke-related events, composite outcome, and mortality in low body weight patients compared to non-low body weight patients (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.17-1.92), (OR 1.55, 95% CI 1.29-1.86), (OR 2.92, 95% CI 1.87-4.58), respectively. There was no significant difference in the safety outcome (major bleeding events) between the DOAC analogs (OR 1.19, 95% CI 0.93-1.52). In this meta-analytical review comprising both real-world and randomized controlled studies, the use of DOAC analogs in low body weight patients (body weight of <60 kg or BMI<18 kg/m2) with atrial fibrillation was associated with increased risks of stroke-related events, composite outcomes, and mortality compared to non-low body weight cohorts patients. At the same time, there was no significant difference in terms of major bleeding events. This finding has provided the first resolution of pervading uncertainty surrounding the use of DOAC analogs in these patient cohorts and suggests the need for follow-up confirmatory systematic studies in this group of patients.

Abstract 12514: Direct Oral Anticoagulants versus Warfarin for Preventing Thromboembolic Events in Valvular Heart Diseases Associated Atrial Fibrillation: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Introduction: Atrial fibrillation (AF) and valvular heart disease (VHD) are common comorbidities, increasing the risk of thromboembolic events. While warfarin has been the standard for preventing stroke in AF patients, direct oral anticoagulants (DOACs) have emerged as an effective substitute. However, their safety and efficacy in VHD patients have yet to be established. Objective: To compare the effectiveness and safety of different DOAC agents versus warfarin in patients with AF and VHD in a network meta-analysis (NMA). Methods: We conducted an online search of databases for eligible studies from inception to April 2023. For dichotomous variables, we calculated the effect size using the risk ratio (RR) and its confidence interval (CI). We conducted frequentist and pairwise meta-analyses using the random-effects model in R-studio software. Results: Seven randomized controlled trials with 17533 patients were included in the review. Analysis of 6 studies showed that dabigatran 150 mg (RR 0.59, 95% CI [0.36, 0.98]) was associated with a lower risk of stroke compared to warfarin. Edoxaban 30 mg was associated with a significantly lower risk of major bleeding (RR 0.43, 95 CI [0.23, 0.81]). Compared to warfarin, dabigatran 110 mg (RR 0.29, 95% CI [0.13, 0.68]), edoxaban 30 mg (RR 0.30, 95% CI [0.11, 0.80]), dabigatran 150 mg (RR 0.36, 95% CI [0.17, 0.77]), edoxaban 60 mg (RR 0.37, 95% CI [0.15, 0.93]), and apixaban (RR 0.40, 95% CI [0.27, 0.61]), were associated with a significantly lower risk of intracranial hemorrhage (ICH). All DOACs did not show any difference in terms of all-cause or cardiovascular mortality, except for rivaroxaban Conclusion: In patients with AF and VHD, Edoxaban 30 mg is the safest DOAC agent associated with a reduced risk of major bleeding, ICH, and GI trouble. Dabigatran 150 mg is associated with a reduced risk of stroke and ICH but with a higher risk of GI trouble. However, Rivaroxaban is associated with an increased risk of systemic embolism.

PB0033 Validated in vivo Model to Assess Direct Oral Anticoagulant Reversal Agents

PB0033 Validated in vivo Model to Assess Direct Oral Anticoagulant Reversal Agents

Clinical Features and Impact on One Year Prognosis of Prescribing Low Doses of Direct Oral Anticoagulant Agents in a Middle Eastern Population with Atrial Fibrillation: Analysis from the Jordan Atrial Fibrillation Study

IntroductionDirect oral anticoagulant agents (DOACs) are indicated for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Reduced doses of DOACs are indicated in patients who have renal impairment and according to age and weight criteria. The aim of this study was to investigate the frequency, clinical factors, and impact on 1-year prognosis of underdosing DOACs. MethodsData of patients enrolled in the Jordan AF (JoFib) study and who were followed for 1 year was used to compare patients prescribed standard dose with those who were underdosed. ResultsThere were 672 patients (76.2%) who were prescribed standard dose and 210 patients (23.8%) who were underdosed. Baseline characteristics were similar between the 2 groups. Factors associated with underdosing were enrollment from an outpatient vs hospital site, moderate- or high-risk HAS-BLED score, an abnormal left ventricular ejection fraction (LVEF <50%), a history of heart failure, or current use of diuretics. At 1 year, the incidence of all-cause mortality was 12.2% in standard dose vs 13.3% in the underdose group (P = .82), stroke or systemic embolism was 3.6% in the standard dose vs 3.8% in the underdose group (P = .67), and major bleeding was 2.2% in the standard dose vs 3.3% in the underdose group (P = .35). ConclusionsAbout (25%) of patients were underdosed. Factors associated with underdosing were outpatient (vs hospital) center enrollment, moderate- or high-risk HAS-BLED score, abnormal LVEF (<50%), history of heart failure, and current use of diuretics. There were no significant differences in the incidence of adverse events of mortality and major morbidity at 1-year follow-up between the standard dose and the underdose groups.

Outcomes and Safety of Direct Oral Anticoagulants (DOACs) versus Vitamin K Antagonists (VKAs) amongst Patients with Valvular Heart Disease (VHD): A Systematic Review and Meta-Analysis

Background: Both valvular heart disease (VHD) and atrial fibrillation (AF) frequently coexist. AF is an important cause of arrhythmias with a definitive cardiovascular morbidity. The use of either vitamin K antagonists (VKAs/warfarin) or direct oral anticoagulants (DOACs) (also known as new oral anticoagulants (NOACs)) has been the mainstay for preventing stroke and systemic embolism in patients with VHD and/or AF, and this has been broadly discussed. However, there are limited studies on anticoagulation therapy for patients with valvular atrial fibrillation (VAF). The main aim of this meta-analysis was to evaluate the outcomes (stroke–vascular events and intracranial bleeding) following DOAC and VKA treatment amongst patients with VAF. Methods: We identified clinical trials and observational studies published in the last 10 years. A systematic review and a meta-analysis were performed to evaluate the outcomes of patients with valvular atrial fibrillation following DOAC vs. VKA treatment. Data evaluation was performed using Review Manager 5.4; the endpoints were stroke–vascular events and intracranial bleeding following DOAC and VKA treatment amongst VAF patients. Risk ratios (RR) were evaluated with 95% confidence intervals. Using random effects models, forest plots were obtained. Heterogeneity was assessed by using the I2 statistic. Results: Eight studies were included in this metanalysis, and a total of fifteen thousand two hundred and fifteen patients (DOAC (8732) and VKA (6483)) were pooled. We found a significant risk reduction in stroke–vascular events when using DOACs in comparison with using VKAs (pooled RR: 0.76; 95% CI: 0.64–0.90, p = 0.002). A total of 14862 patients (DOAC (8561) and VKA (6301)) were pooled from a total of six studies for intracranial bleeding. We found a significant risk reduction in terms of intracranial bleeding when using DOACs in comparison with using VKAs (pooled RR: 0.43; 95% CI: 0.24–0.77, p ≤ 0.05). Conclusions: When compared to VKAs, DOAC agents were found to have less risk of stroke–vascular events and intracranial bleeding. Further prospective studies are essential to establish the efficacy and safety of DOAC agents in patients with various subtypes of VAF.

Pre-hospital use of direct oral anticoagulants agents is associated with a lower risk of major bleeding events in critically ill patients: A single academic center experience

BackgroundThe last decade has witnessed significant advancements in direct oral anticoagulants (DOACs), transforming the landscape of anticoagulation therapy. With the uptrend in DOACs use, critical care physicians are encountering more patients with pre-hospital DOACs prescription. Safety and real world outcomes-related data on DOACs use in critically ill patients are scarce. ObjectiveWe assess the risk of major bleeding (MB) events and patient-centered outcomes with pre-hospital use of direct oral anticoagulant agents (DOACs) compared to warfarin therapy. MethodsObservational study in a single large academic center from January 1st, 2012, through May 4th, 2018. We included adult critically ill patients with warfarin or one of the DOACs, as active medications at the time of hospital admission. The primary outcome was major bleeding (MB), based on the ISTH criteria Results99,481 patients were screened; 558 and 3037 patients were included in the final analysis for the DOAC and warfarin groups, respectively. Multivariable analysis showed that the pre-hospital use of DOACs was associated with lower odds for major bleeding events, GI bleeding, need for endoscopic intervention, hemorrhagic shock, any blood transfusion; but higher odds of intracranial bleeding, as compared to warfarin use. There was no difference in hospital length of stay or ICU-free days. ConclusionsPre-hospital use of DOACs among critically ill patients is associated with lower major bleeding events, GI bleeding, need for endoscopic intervention, and blood transfusion but a higher risk for intracranial bleeding.

A 65-Year-Old Man with Bilateral Adrenal Hemorrhage Following Prophylaxis for Postoperative Deep Vein Thrombosis with Rivaroxaban.

BACKGROUND Direct oral anticoagulant (DOAC) agents, such as rivaroxaban, treat and prevent venous thrombosis. Although adrenal hemorrhage due to DOACs has previously been reported, this is a rare condition that can present as an emergency. In this case report, we present a 65-year-old man who recently had bilateral knee arthroplasty and was started on rivaroxaban 10 mg daily for deep vein thrombosis (DVT) prophylaxis following the surgery. CASE REPORT Ten days after bilateral knee arthroplasty and starting rivaroxaban, the patient presented to the Emergency Department with severe, sudden abdominal pain. Abdominal computed tomography detected significantly enlarged bilateral adrenals, with ill-defined heterogeneous density extending to the upper part of perinephric and paranephric spaces, suggesting bilateral adrenal hemorrhage. A cosyntropin stimulation test was used to confirm the suspicion of adrenal insufficiency. Cortisol levels were 66 nmol/L before stimulation and 83 nmol/L 60 min after cosyntropin administration. Hydrocortisone was started intravenously at a dose of 50 mg every 8 h. After his symptoms improved, he was discharged on oral hydrocortisone at 10 mg in the morning and 5 mg in the evening. Seven weeks after discharge, follow-up abdominal ultrasonography showed that the bilateral adrenal hemorrhage had resolved. CONCLUSIONS This case supports previous cases of adrenal hemorrhage as a rare but serious association with rivaroxaban and highlights the importance of rapid diagnosis using imaging and monitoring of patients for this possible adverse effect. Practitioners must remain vigilant when prescribing anticoagulation therapy, especially in patients who are at an increased risk for adrenal hemorrhage.

Oral Anticoagulants after Heart Transplantation-Comparison between Vitamin K Antagonists and Direct Oral Anticoagulants.

Patients after heart transplantation (HTX) often require oral anticoagulants (OACs) due to atrial arrhythmias or thromboembolic events but little is known about the post-transplant use of direct oral anticoagulants (DOACs). We investigated the frequency, indications, and complications of DOACs and vitamin K antagonists (VKAs) after HTX. We screened all adult patients for the use of post-transplant OACs who underwent HTX at Heidelberg Heart Center between 2000 and 2021. Patients were stratified by type of OAC (DOAC or VKA) and by DOAC agents (apixaban, dabigatran, edoxaban, or rivaroxaban). Indications for OACs comprised atrial fibrillation, atrial flutter, pulmonary embolism, upper and lower extremity deep vein thrombosis, as well as intracardiac thrombus. A total of 115 of 459 HTX recipients (25.1%) required OACs, including 60 patients with DOACs (52.2%) and 55 patients with VKAs (47.8%). Concerning DOACs, 28 patients were treated with rivaroxaban (46.7%), 27 patients with apixaban (45.0%), and 5 patients with edoxaban (8.3%). We found no significant differences between both groups concerning demographics, immunosuppressive drugs, concomitant medications, indications for OACs, ischemic stroke, thromboembolic events, or OAC-related death. Patients with DOACs after HTX had a significantly lower one-year rate of overall bleeding complications (p = 0.002) and a significantly lower one-year rate of gastrointestinal hemorrhage (p = 0.011) compared to patients with VKAs after HTX in the Kaplan-Meier estimator. DOACs were comparable to VKAs concerning the risk of ischemic stroke, thromboembolic events, or OAC-related death but were associated with significantly fewer bleeding complications in HTX recipients.

#3662 FREQUENCY OF INR TESTING IN HEMODIALYSIS PATIENTS ON VITAMIN K ANTAGONISTS: A RETROSPECTIVE STUDY

Abstract Background and Aims Despite the rising of direct oral anticoagulant agents’ use in the general population, vitamin K antagonists (VKA) are still used in hemodialysis (HD) French patients with atrial fibrillation. These HD patients on VKA have also poor levels of time in therapeutic range. It is recommended generally to follow patients with monthly INR, however there is lack of such evidence in HD. This study aims to analyze the frequency of INR testing needed in HD patients. Method This is a retrospective study of all patients treated with VKA in three French dialysis units between 1st January and 31st December 2022. Patients are followed with weekly INR. Variables collected included over twelve months the number of INR tests, their percentage within target, above target and below target, and number of VKA dose adjustment. Bleedings, transfusions, thrombotic events and antibiotic use were recorded. Linear regression analysis evaluated factors associated with number of VKA dose adjustment per year. This study was conducted in concordance with the Declaration of Helsinki 1975. Results Out of 160 HD patients, 45 (28.1%) were on VKA for paroxysmal or chronic atrial fibrillation. Their characteristics are summarized in Table 1. A total of 2609 INR tests were performed over a year with a mean of 57.9±18.6 per patient. The median number of VKA dose adjustment per year was 11 (8, 13). A significant correlation was found between the number of antibiotics and number of VKA dose adjustment (Spearman Rho = 0.360, p = 0.015). In univariate regression analysis, factors associated with higher numbers of dose adjustment were diabetes, sevelamer and blood flow (Table 2). Bleeding was not significantly different between those with high versus low VKA dose adjustment. Conclusion In this study, 22% of tests led to VKA dose adjustment. Patients with diabetes, on sevelamer, treated with antibiotics and with lower serum albumin needed frequent INR testing more than once monthly. These results could be helpful in contexts with limited resources.

Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infection-associated coagulopathies perturb the hemostatic balance resulting in thrombosis and/or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies. This theme included state-of-the-art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: the value and limitations of ex vivo models. Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularized organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation-associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management. Plenary presentations addressed controversial areas, i.e., thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies, and clinically tested factor XI(a) inhibitors, both possibly with reduced bleeding risk. Finally, COVID-19-associated coagulopathy is revisited.

Choice of Oral Anticoagulant: Outcomes in Atrial Fibrillation Patients Post-Stroke Despite Direct Oral Anticoagulant Use

BackgroundFor patients with atrial fibrillation who have an ischemic stroke or transient ischemic attack (TIA) despite taking direct oral anticoagulants (DOACs), the optimal strategy for ongoing anticoagulation is unknown. MethodsUsing provincial administrative databases in Alberta, Canada, we compared anticoagulant use before/after the breakthrough stroke/TIA and assessed recurrence of stroke/TIA or bleeding, with consideration of medication adherence. Adherence was defined as the proportion of days covered (PDC) being ≥ 80%. ResultsAmong 985 patients, the median age was 80 years (interquartile range 13), with a mean CHADS2 score of 1.7± 1 prior to the index event. Patients were followed for a median of 643 days (interquartile range 836). Following the index stroke/TIA event, 623 patients (63%) filled a prescription for the same DOAC regimen, 83 (8%) filled a prescription for a different dose, 155 (16%) switched DOAC agents, 51 (5%) switched to warfarin, and 73 (7%) filled no oral anticoagulant prescription. Patients who kept the same regimen more commonly had TIA index events (59%); patients who changed dose or drug more often had stroke index events (55%-78%). During follow-up, 135 (14%) had stroke/TIA recurrence, and 46 (5%) had bleeding; rates of each did not differ between prescribing patterns. Post-index event, the proportion of patients with a proportion of days covered ≥ 80% improved from 55% to 80%. ConclusionsAlthough most maintained the same DOAC regimen after stroke/TIA, rates of recurrent stroke/TIA and bleeding were similar across prescribing patterns. Stroke/TIA severity may have influenced prescribing practices. DOAC prescription adherence improved poststroke/TIA and signals an opportunity for optimization in patients with atrial fibrillation.

Is There a Role for Vitamin K Antagonist in the Management of Atrial Fibrillation in 2023?

To address the following question: Are vitamin K antagonists (VKA) obsolete as stroke prevention therapy for patients with atrial fibrillation (AF) and thromboembolic risk factors? A patient-level meta-analysis of the pivotal phase III randomized trials confirmed the favorable treatment effect of direct oral anticoagulants (DOAC) over VKA in multiple key patient subgroups. Among patients with AF and rheumatic heart disease (85% of whom had mitral stenosis), a randomized trial showed that rivaroxaban was not superior to VKA for stroke prevention. Caution should be exercised when prescribing DOAC for AF-related stroke prevention for patients with elevated body mass indices or history of bariatric surgery, patients with bioprosthetic heart valves, and those who require treatment with drugs that interact with cytochrome P450 and P-glycoprotein. Drug costs associated with DOAC remain considerably higher than VKA, by up to 30-fold. Direct oral anticoagulants are preferable over VKA in the large majority of eligible patients with AF and thromboembolic risk factors. The use of DOAC should be avoided for patients with mechanical heart valves or moderate/severe rheumatic mitral stenosis. Vitamin K antagonist is a reasonable option for patients who are under-represented in randomized trials, when there are significant drug-drug interactions or when patients cannot afford DOAC agents due to their higher costs.

Reversal agents for current and forthcoming direct oral anticoagulants

Over the past 20 years, there has been a shift from vitamin K antagonists to direct oral anticoagulants (DOACs), which include the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban. Although DOACs are associated with less serious bleeding than vitamin K antagonists, bleeding still occurs with DOACs, particularly in the elderly and in those with comorbidities. Reversal of the anticoagulant effects of the DOACs may be needed in patients with serious bleeding and in those requiring urgent surgery or intervention. Reversal can be effected with specific agents, such as idarucizumab for dabigatran and andexanet alfa for apixaban, edoxaban, and rivaroxaban, or with non-specific agents, such as prothrombin complex concentrates, activated prothrombin complex concentrate, and recombinant activated factor VII. This paper (i) provides an update on when and how to reverse the DOACs, (ii) describes new reversal agents under development, and (iii) provides a strategic framework for the reversal of the factor XI inhibitors currently under investigation in phase three clinical trials.

When and How to Use Reversal Agents for Direct Oral Anticoagulants?

Our objective is to describe currently available reversal agents for direct oral anticoagulants (DOACs), their target population, the available clinical practice recommendations and future directions. Specific (idarucizumab for dabigatran and andexanet alfa for direct factor Xa inhibitors) and non-specific (prothrombin complex concentrates) reversal agents are effective in neutralizing the anticoagulant effect of DOACs. New investigational antidotes such as ciraparantag and VMX-C001 offer an alternative to andexanet alfa in reversing the anticoagulant activity of direct oral factor Xa inhibitors, but more clinical data are needed before they could be licensed for use. Specific reversal agents are recommended for use in clinical situations within their licensed indications (i.e.: reversal of DOACs in patients with severe uncontrolled or life-threatening bleeding or in need of emergency surgery or other invasive procedures), while non-specific reversal agents may be used when specific antidotes are not available or indicated.

A retrospective evaluation of direct oral anticoagulant (DOAC) management strategies in patients with cancer on active chemotherapy.

Use of direct oral anticoagulants (DOACs) in patients with cancer on active chemotherapy is challenging due to changes in renal or hepatic function, thrombocytopenia, chemotherapy-induced nausea and vomiting (CINV), and drug-drug interactions (DDIs) attributed to disease or treatment. The purpose of this retrospective cohort analysis was to characterize DOAC management through various interventions and evaluate the efficacy and safety of DOAC use in this patient population. A total of 58 patients with 97 unique index periods in which a patient was concomitantly on a DOAC and chemotherapy were identified. Several instances were observed in which an intervention should be made based on manufacturer guidance or clinical judgment. Of 37 instances attributed to changes in renal function, the following interventions were employed: dose adjustments (10/37), holding DOAC therapy until renal function improved (held 3/37, restarted 4/37), changing to an alternative anticoagulant (5/37), DOAC discontinuation (2/37), or no change (13/37). One change was made in response to decreased hepatic function (1/15). DOACs were held in the setting of platelet counts below 50K/mm3 (8/20) and restarted when platelets improved above this threshold (5/20). In patients with CINV, DOAC therapy was continued (26/32) with few changes made. To manage DOAC-chemotherapy DDIs, changes in DOAC agents (4/6) and dose reductions in chemotherapy agents (2/6) were made. Thrombotic and bleeding events did not strongly correlate with renal or hepatic impairment, thrombocytopenia, CINV, or DDIs. Further guidance regarding the use of these agents in this patient population is warranted to address management strategies, efficacy, and safety. Use of direct oral anticoagulants (DOACs) in patients with cancer on active chemotherapy is challenging due to changes in renal or hepatic function, thrombocytopenia, chemotherapy-induced nausea and vomiting (CINV), and drug-drug interactions (DDIs) attributed to disease or treatment. The purpose of this retrospective cohort analysis was to characterize DOAC management and evaluate the efficacy and safety of DOAC use in this patient population. A total of 58 patients with 97 unique index periods in which a patient was concomitantly on a DOAC and chemotherapy were identified. Several instances were observed in which an intervention should be made based on manufacturer guidance or clinical judgment. Interventions employed are summarized graphically. Thrombotic and bleeding events did not strongly correlate with renal or hepatic impairment, thrombocytopenia, CINV, or DDIs. CINV chemotherapy-induced nausea and vomiting, DDIs drug-drug interactions, DOAC direct oral anticoagulant, OAC oral anticoagulant.

Practical Guide for Anticoagulant and Antiplatelet Reversal in Clinical Practice

In recent years, anticoagulant and antiplatelet use have increased over the past years for the prevention and treatment of several cardiovascular conditions. Due to the rising use of antithrombotic medications and the complexity of specific clinical cases requiring such therapies, bleeding remains the primary concern among patients using antithrombotics. Direct oral anticoagulants (DOACs) include rivaroxaban, apixaban, edoxaban, and betrixaban. Direct thrombin inhibitors (DTIs) include argatroban, bivalirudin, and dabigatran. DOACs are associated with lower rates of fatal, life-threatening, and significant bleeding risks compared to those of warfarin. The immediate reversal of these agents can be indicated in an emergency setting. Antithrombotic reversal recommendations are still in development. Vitamin K and prothrombin complex concentrate (PCCs) can be used for warfarin reversal. Andexanet alfa and idarucizumab are specific reversal agents for DOACs and DTIs, respectively. Protamine sulfate is the solely approved reversal agent for unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). However, there are no specific reversal agents for antiplatelets. This article aims to provide a practical guide for clinicians regarding the reversal of anticoagulants and antiplatelets in clinical practice based on the most recent studies.