Safety Of Direct Oral Anticoagulants Research Articles

Risk of Intracranial Hemorrhage Associated With Direct Oral Anticoagulation vs Antiplatelet Therapy

For patients with atrial fibrillation, clinicians often prescribe antiplatelet therapy rather than oral anticoagulation, which may be related to a concern that direct oral anticoagulants (DOACs) are associated with a higher risk of intracranial bleeding, despite being less effective for stroke prevention. To determine whether DOAC therapy, compared with single-agent antiplatelet therapy, was associated with an increased risk of intracranial and major hemorrhage. A systematic search of PubMed and Embase databases from inception to February 7, 2024, was performed. Randomized clinical trials that compared DOAC therapy with single-agent antiplatelet therapies were included. Trials with active follow-up of less than 30 days or a sample size less than 200 were excluded. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Data were extracted independently by 2 researchers. A random-effects meta-analysis model was used to report pooled treatment effects and 95% CIs. The primary outcome was occurrence of intracranial hemorrhage. A total of 9 randomized clinical trials were included (45 494 participants). DOAC therapy was not associated with significantly higher odds of intracranial hemorrhage compared with antiplatelet therapy (0.55% vs 0.48% over a mean trial follow-up of 17.1 months; odds ratio [OR], 1.15; 95% CI, 0.71-1.88), but there was heterogeneity among trials (I2 = 53.7%). In an analysis by DOAC agent, the respective estimates for intracranial hemorrhage risk were as follows: rivaroxaban, OR, 2.09 (95% CI, 1.20-3.64); dabigatran, OR, 1.00 (95% CI, 0.61-1.64); and apixaban, OR, 0.72 (95% CI, 0.44-1.17). Overall, DOAC therapy was associated with higher odds of major hemorrhage compared with antiplatelet therapy (2.41% vs 1.76% over a mean trial follow-up of 15.5 months; 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); and apixaban, OR, 1.09 (95% CI, 0.73-1.63). In this systematic review and meta-analysis, DOAC therapy was not associated with a significantly higher risk of intracranial hemorrhage compared with antiplatelet therapy, but was associated with a higher risk of major hemorrhage. These findings support the safety of DOAC compared with antiplatelet therapy with respect to risk of ICH and reinforce adherence with current atrial fibrillation guidelines.

Efficacy and safety of novel anticoagulant therapies in patients with chronic kidney disease-asystematic review and meta-analysis.

Chronic Kidney Disease (CKD) significantly increases the risk of cardiovascular diseases, including atrial fibrillation, which usually requires anticoagulant therapy. The effectiveness and safety of direct oral anticoagulants compared to vitamin K antagonists in patients with CKD remain insufficiently studied, particularly in the more advanced stages. This systematic review, registered in PROSPERO (CRD42023410192), adhered to PRISMA guidelines and included randomized clinical trials and cohort studies comparing direct oral anticoagulants and vitamin K antagonists in CKD patients. Major databases were searched, and studies were selected based on strict inclusion criteria. A meta-analysis was performed using random-effects models. Twenty-three studies with a total of 465,673 CKD patients were included. Direct oral anticoagulants showed a significant reduction in major bleeding events compared to vitamin K antagonists (Relative Risk [RR] = 0.62, 95% Confidence Interval: 0.49-0.79, p < 0.01) and a non-significant trend toward reducing thromboembolic events (RR = 0.69, 95% Confidence Interval: 0.43-1.14, p = 0.11). Furthermore, direct oral anticoagulants were associated with a significant reduction in all-cause mortality (RR = 0.63, 95% Confidence Interval: 0.43-0.91, p = 0.02). Direct oral anticoagulants may offer a safe alternative to vitamin K antagonists in CKD patients, particularly in terms of reducing bleeding risks and potentially improving survival. However, their role in preventing thromboembolic events remains uncertain, highlighting the need for further research, especially in patients with advanced CKD and kidneyfailure.

MANAGEMENT OF ANTICOAGULATION IN ATRIAL FIBRILLATION: MINIMIZING DRUG INTERACTIONS WITH DOACS

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia that elevates the risk of thromboembolic events, necessitating effective anticoagulation strategies. Direct oral anticoagulants (DOACs) have become the preferred choice due to their safety profiles; however, drug interactions can compromise their efficacy and safety. Objective: This study aims to assess the impact of drug interactions on the efficacy and safety of DOACs in patients with AF. Method: A literature review was conducted using databases such as the Virtual Health Library, LILACS Plus, and Medline, focusing on articles published from 2019 to 2024. Inclusion criteria emphasized studies related to drug interactions involving DOACs and AF, resulting in the selection of 13 relevant articles. Results: The analysis revealed a significant prevalence of drug interactions among patients treated with DOACs. Co-prescription with CYP3A4 inhibitors and P-glycoprotein modulators was linked to increased bleeding risks. Factors such as age, renal function, and the presence of comorbidities were crucial in determining appropriate dosing and the risk of adverse events. Conclusion: Careful management of AF patients on DOACs is vital to mitigate risks associated with drug interactions. Personalized treatment approaches that consider individual clinical profiles and ongoing education for healthcare providers are essential to optimize anticoagulation therapy.

Safety of direct oral anticoagulants in patients with atrial fibrillation aged 80 years and older: clinical risk factors

BACKGROUND: Direct oral anticoagulants (DOACs) are associated with bleeding, particularly in the geriatric population. Most studies focus on predicting major bleeding, but clinically relevant non-major bleeding (CRNMB) is equally important in practice. АIM: To assess the ability of clinical factors to predict the risk of CRNMB with the use of DOACs in patients with atrial fibrillation (AF) aged 80 years and older. MATERIALS AND METHODS: A total of 367 patients on DOACs with non-valvular AF aged 80 years and older were evaluated; the median age was 84 [82; 88] years. Key characteristics of the groups were analyzed, including gender, age, and body mass index. CHA2DS2-VASc and HAS-BLED scales were used to assess the risk of ischemic stroke and bleeding, respectively. Comorbidities, Charlson Comorbidity Index, and risk factors of chronic non-communicable diseases were considered. In addition, number of medications taken, physical examination data, history of atherosclerosis, and laboratory test results were collected. RESULTS: In univariate analysis, significant risk factors for the development of CRNMB with all DOACs included higher walking frequency (p=0.022), lower heart rate (p=0.08), and history of gastric and duodenal ulcer [odds ratio 5.34; 95% confidence interval (CI) 2.31–12.0; p 0.001]. In multivariate analysis, a model for predicting CRNMB was developed using age, type of DOAC, liver disease, acute cerebrovascular accident, history of gastric and duodenal ulcer as predictors. The resulting model had a predictive accuracy of 62.6% (95% CI 57.4–67.6), a sensitivity of 66.5% (95% CI 59.4–73.1), and a specificity of 58.2% (95% CI 50.4–65.7). CONCLUSION: The study identified specific modifiable, potentially modifiable, and non-modifiable risk factors for developing CRNMB in AF patients aged 80 years and over taking DOACs. An electronic system to support medical decision making, risk factor management, and public quality of life can be created using results of the study.

Comparative safety and effectiveness of oral anticoagulants in patients with non-valvular atrial fibrillation and high risk of gastrointestinal bleeding: A nationwide French cohort study.

This observational study compared effectiveness and safety of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) or vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) at high risk for gastrointestinal bleeding (GIB). Anticoagulant-naïve adults with NVAF with ≥1 GIB risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible. Outcomes included major bleeding (MB) and stroke/systemic embolism (SE). Patient characteristics were balanced using propensity score matching. A total of 314,184 patients were identified with 162,150 (51.5%) in the apixaban cohort, 88,427 (28.1%) in the rivaroxaban cohort, 16,465 (5.2%) in the dabigatran cohort, and 47,142 (15.0%) in the VKA cohort (mean age 79.0 years, standard deviation 10.5; 51.0% female). A total of 45,124 apixaban-VKAs, 38,737 rivaroxaban-VKAs, 16,415 dabigatran-VKAs, 88,414 apixaban-rivaroxaban, 16,464 apixaban-dabigatran, and 16,459 rivaroxaban-dabigatran pairs were retained after propensity score matching. Apixaban had lower risk of MB versus dabigatran (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.83) and rivaroxaban (HR, 0.63; 95% CI, 0.59-0.66). Apixaban had lower risk of GIB versus dabigatran (HR, 0.46; 95% CI, 0.37-0.56) and rivaroxaban (HR, 0.54; 95% CI, 0.49-0.59). Risk of GIB was similar with dabigatran versus rivaroxaban (HR, 1.05; 95% CI, 0.89-1.24). Apixaban had lower risk of stroke/SE versus rivaroxaban (HR, 0.90; 95% CI, 0.84-0.96), while risk was similar versus dabigatran (HR, 1.1; 95% CI, 0.9-1.3). All DOACs had lower risk of MB and stroke/SE versus VKAs (p<0.001 for all). DOACs had improved safety and effectiveness from bleeding and stroke/SE, respectively, versus VKAs among patients with NVAF at high risk for GIB. Apixaban was associated with lower MB and GIB risk versus other DOACs. For stroke/SE, apixaban was associated with reduced risk versus rivaroxaban and similar risk versus dabigatran.

Efficacy of direct oral anticoagulants vs. warfarin in left ventricular thrombus in myocardial infarction: systematic review and meta-analysis.

Current recommendations for antithrombotic strategies in left ventricular (LV) thrombus following myocardial infarction (MI) remain uncertain. This study aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to warfarin in LV thrombus following MI. A systematic search using four databases, including PubMed, Embase, Web of Science, and Cochrane CENTRAL, was conducted from inception to 8 July 2024, without language restrictions. The inclusion criteria were studies that included patients with LV thrombus following MI and compared the efficacy or safety of DOACs and warfarin. There were 11 studies (3 randomized and 8 nonrandomized) included in this meta-analysis, involving 14 927 participants. We used a random-effects model for this meta-analysis. DOACs were associated with higher thrombus resolution than warfarin, with a risk ratio (RR) of 1.07 [95% confidence interval (CI) 1.00-1.15], P = 0.04. Similarly, DOACs were associated with a lower rate of stroke and systemic embolism, with an RR of 0.84 (95% CI 0.78-0.90), P < 0.01. DOACs also marginally reduced the rate of major bleeding compared with warfarin, with an RR of 0.87 (95% CI 0.75-1.00), P = 0.05. DOACs were associated with higher rates of LV thrombus resolution, lower rates of stroke/systemic embolism, and marginally reduced major and bleeding events compared with warfarin in patients with LV thrombus following acute MI. Therefore, DOACs may be a reasonable alternative to warfarin in this setting.

Efficacy and Safety of Direct Oral Anticoagulants Compared to Warfarin in Patients with Cirrhosis and Splanchnic Vein Thrombosis.

The incidence of splanchnic vein thrombosis (SVT) is reported to be <25 times lower than that of deep vein thrombosis and pulmonary emboli, which occur in 70 to 270/100,000 cases in the general population. Current guidelines recommend initial treatment with therapeutic low-molecular-weight heparin followed by a transition to a vitamin K antagonist (VKA) or a direct oral anticoagulant (DOAC) in patients with cirrhosis who develop SVT without severe liver dysfunction. This, however, is based on observational data. This study aimed to evaluate the efficacy and safety of anticoagulant therapy in patients with cirrhosis who present with SVT and receive either a DOAC or a VKA. This multicenter retrospective cohort study was conducted from December 2021 to November 2022. Patients between the ages of 18 and 75 years with cirrhosis and acute SVT who received either a VKA or a DOAC between July 2019 and July 2021 were eligible for inclusion. The primary outcome was the efficacy of treatment, defined as a new thrombotic event. The secondary outcome was the safety of treatment, defined as the development of major bleeding. Readmission data were followed up at 6 and 10 months. Bivariate analysis was conducted to assess the relationship between the medication groups and each outcome and summarized as odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was set at 5% for all of the comparisons. A total of 80 patients from 50 hospitals were included in this study. Sixty-one patients (59.02% male) received DOACs and 19 (57.89% male) received a VKA. Of the patients who received DOACs, 41 (67.21%) received apixaban, one (1.64%) received dabigatran, and 19 (31.15%) received rivaroxaban. The results from the bivariate analysis revealed no significant differences between DOACs and warfarin for both the efficacy (OR 1.46, 95% CI 0.44-4.84, P = 0.53) and safety outcomes (OR 1.03, 95% CI 0.04-26.43, P = 1) at 10 months. The use of DOACs in patients with cirrhosis who present with SVT may be efficacious and safe compared with warfarin. The findings from our study may inform power analyses for well-conducted randomized trials to confirm these findings.

Direct oral anticoagulants or warfarin in patients with left ventricular thrombus: a meta-analysis of randomized clinical trials

Abstract Background/Introduction There are limited randomized controlled trials (RCTs) data on the use of direct oral anticoagulants (DOAC) versus warfarin in patients with left ventricular (LV) thrombus. Current AHA and ESC guidelines recommend oral anti-coagulants (either DOAC or warfarin) for 3 to 6 months without any preference. Purpose We aimed to compare outcomes with DOACs versus warfarin in patients with LV thrombus. Methods A comprehensive literature search was performed from inception to 02/01/2024 of the PubMed database. RCTs of adult patients comparing DOAC to warfarin were evaluated for mortality, major bleeding, stroke, and LV thrombus resolution. Meta-analytic Odds ratio (OR) with 95% confidence intervals (CI) were calculated using DerSimonian-Laird method. Results From 100 studies, four RCTs with 188 subjects (95 DOAC and 93 warfarin) were included with mean age of 53.4 years, 69.5% males, and mean follow up 5.03 months. There was no difference in mortality (OR= 0.67 [95% CI 0.15-3.06]; p=0.60; I2=0%; 3 trials), stroke (OR= 0.46 [95% CI 0.09-2.44]; p=0.37; I2=0%; 4 trials), major bleeding (OR= 0.43 [95% CI 0.12-1.55]; p=0.20; I2=0%; 4 trials), and LV thrombus resolution (OR= 1.33 [95% CI 0.45-3.95]; p=0.61; I2=0%; 2 trials) with use of DOAC compared to warfarin (Figure Panel A to D). Overall, there was no evidence of publication bias using either funnel plot or eggers test (p &amp;gt; 0.05). Conclusions In this meta-analysis of 4 RCTs, there was similar efficacy and safety of DOAC and warfarin in patients with LV thrombus. However, the evidence is limited by small sample size with lesser precision in the estimates. Future large-scale trials are needed to confirm these findings.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin among Nursing Home Residents with Atrial Fibrillation: A Retrospective Cohort Study

ObjectiveResidents of nursing homes are usually excluded from clinical trials, including trials to assess treatments for common conditions such as nonvalvular atrial fibrillation (NVAF). We aimed to quantify the real-world comparative safety and effectiveness of direct-acting oral anticoagulants (DOACs) vs warfarin among nursing home residents with NVAF. DesignRetrospective cohort study using 100% national Minimum Data Set and linked Medicare claims from January 2011 through December 2018. Setting and ParticipantsLong-term care nursing home residents aged ≥66 years enrolled in fee-for-service Medicare. We included individuals diagnosed with NVAF newly initiating oral anticoagulants. MethodsWe identified exposure to DOACs (apixaban, dabigatran, rivaroxaban, and edoxaban) vs warfarin. Outcomes were hospitalization for ischemic stroke/systemic embolism, major bleeding, pneumonia (negative control outcome), and all-cause death. We used inverse probability of treatment weighting competing risk regression models for clinical outcomes and Cox proportional hazards regression for all-cause death. ResultsOf 38,983 individuals newly initiating anticoagulants, 19,366 (49.7%) initiated DOACs and 19,617 (50.3%) initiated warfarin. In the inverse probability of treatment weighting analysis, compared with warfarin, there was no statistically significant association between DOAC use and ischemic stroke/systemic embolism [4.5 vs 4.7 events per 100 person-years; adjusted hazard ratio (aHR), 0.94; 95% CI, 0.84–1.05] or major bleeding (12.6 vs 12.4 events per 100 person-years; aHR, 1.03; 95% CI, 0.96–1.10). DOACs use was associated with a modest but statistically significant lower risk of all-cause death (48.1 vs 49.0 events per 100 person-years; IPTW analysis aHR, 0.95; 95% CI, 0.91–0.98). Conclusions and ImplicationsAmong nursing home residents with NVAF, DOACs and warfarin were associated with a similar risk of ischemic stroke/systemic embolism and major bleeding. However, the use of DOACs was associated with a slightly reduced risk of all-cause mortality.

Direct oral anticoagulant approvals by four major regulatory agencies: a cross-sectional analysis of premarket and postmarket evidence

ObjectivesTo compare the premarket and postmarket evidence of safety and efficacy of direct oral anticoagulants approved for stroke prevention in atrial fibrillation patients across four major regulatory agencies.DesignCross-sectional.SettingEuropean Medicines Association...

Comparison of Oral Anticoagulants vs. Warfarin for Stroke Prevention in Atrial Fibrillation: A Meta-Analysis

Background: Atrial fibrillation (AF) significantly increases the risk of ischemic stroke, necessitating effective anticoagulation therapy. Warfarin has been the standard treatment, but direct oral anticoagulants (DOACs) have emerged as a safer and more effective alternative.Objective: To compare the efficacy and safety of DOACs versus warfarin in stroke prevention among AF patients.Methods: A comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus following PRISMA guidelines. Randomized controlled trials and observational studies comparing DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) with warfarin in AF patients were included. Primary outcomes were ischemic stroke or systemic embolism, and secondary outcomes included all-cause mortality, major bleeding, intracranial hemorrhage (ICH), and gastrointestinal bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model.Results: A total of 35 studies involving 172,350 patients were analyzed. DOACs significantly reduced ischemic stroke or systemic embolism (HR: 0.78, 95% CI: 0.72–0.84, p &lt; 0.001) and all-cause mortality (HR: 0.85, 95% CI: 0.79–0.92, p = 0.002). Major bleeding risk was lower (HR: 0.88, 95% CI: 0.80–0.96, p = 0.005), but gastrointestinal bleeding was higher (HR: 1.20, 95% CI: 1.10–1.30, p &lt; 0.001).Conclusion: DOACs provide superior efficacy and safety in stroke prevention compared to warfarin, despite a higher risk of gastrointestinal bleeding.

Effect of impaired kidney function on outcomes and treatment effects of oral anticoagulant regimes in patients with atrial fibrillation in a real-world registry.

The impact of impaired kidney function on outcomes and treatment benefits of vitamin-K antagonists (VKA) versus direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) has insufficiently been investigated in randomized controlled studies (RCTs). Most studies and registries are either biased due to incomplete enrolment of consecutive patients in large pharma industry sponsored registries, or due to short recruitment periods or incomplete assessment of important variables in national registries. This study uses data from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB), a retrospective single-center registry of 10,222 consecutive patients with AF presenting to the emergency department of University Hospital of Heidelberg from June 2009 until March 2020. Rates of all-cause mortality, stroke, major bleeding and myocardial infarction (MI) were related to the presence and severity of impaired presenting kidney function, as well as to assigned treatment with VKA vs. DOAC. The risks for all-cause mortality (HR: 3.26, p<0.001), stroke (HR: 1.58, p<0.001), major bleeding (HR: 2.28, p<0.001) and MI (HR: 2.48, p<0.001) were significantly higher in patients with an eGFR<60 ml/min at admission and increased with decreasing eGFR. After adjustment for variables of CHA2DS2VASc-score, presence of eGFR <60 ml/min remained as an independent predictor for all-cause mortality, major bleeding and MI. The hazard ratio (HR) for all-cause mortality, major bleedings and MI was significantly lower in patients receiving DOAC compared to VKA. Findings from our large real-life registry confirm the data from RCTs and extend our knowledge on the effectiveness and safety of DOACs to subjects that were underrepresented in RCTs.

Rethinking the use of direct oral anticoagulants for secondary thromboprophylaxis in patients with thrombotic antiphospholipid syndrome.

Patients with thrombotic antiphospholipid syndrome (APS) are at high risk for recurrent thrombosis, and indefinite anticoagulation is recommended. Patients with APS merit indefinite anticoagulation, and vitamin K antagonists (VKAs) have historically been the standard treatment. Direct oral anticoagulants (DOACs) present an appealing alternative to VKAs. Due to their pharmacokinetic and pharmacodynamic characteristics, DOACs offer advantages over VKAs, namely the lack of need for laboratory monitoring, the usage of a fixed dosage, and the absence of significant interaction with dietary components and drugs. The efficacy and safety of DOACs in patients with APS have been studied in four phase II/III clinical trials (three with rivaroxaban and one with apixaban). These studies showed DOACs' inferiority compared to VKAs in preventing recurrent thrombosis. Recurrence was significantly greater in patients with arterial thrombotic events and a triple positivity for antiphospholipid antibodies. No differences were observed in the incidence of venous thromboembolism between both groups. Major bleeding was similar in patients treated with DOACs or VKAs. Several observational studies have reported similar results. This review aims to analyse the existing evidence on the efficacy and safety of DOACs for secondary prevention in patients with APS.

Comparative effectiveness and safety of direct oral anticoagulants and warfarin in atrial fibrillation patients with dementia.

Developing an effective stroke prevention strategy is crucial for elderly atrial fibrillation (AF) patients with dementia. This is due to the limited and inconsistent evidence available on this topic. In this nationwide, population-based cohort study, we aim to compare the effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in AF patients with dementia. We identified AF patients with dementia, aged 50 years or older, from Taiwan's National Health Insurance Research Database between 2010 and 2019. The primary outcome was a composite of hospitalizations due to ischemic stroke, acute myocardial infarction, intracranial hemorrhage, or major bleeding, as well as all-cause mortality. We used 1:1 propensity score matching and Cox proportional hazard models to adjust for confounding factors when comparing outcomes between warfarin and DOAC (apixaban, dabigatran, edoxaban, or rivaroxaban) users or warfarin and each individual DOAC. There were 2952 patients in the DOAC-warfarin matched cohort. The apixaban-, dabigatran-, edoxaban-, and rivaroxaban-warfarin matched cohorts had 2346, 2554, 1684, and 2938 patients, respectively. The DOAC group, when compared to warfarin, was associated with a lower risk of both the composite outcome (hazard ratio (HR), 0.81; 95% confidence interval (CI) 0.69-0.95) and ischemic stroke (HR 0.65; 95% CI 0.48-0.87). Apixaban (HR 0.79; 95% CI 0.66-0.94), dabigatran (HR 0.64; 95% CI 0.53-0.77), and rivaroxaban (HR 0.82; 95% CI 0.70-0.97) were also associated with a lower risk of the composite outcome. Compared to warfarin, DOACs, whether as a group or apixaban, dabigatran, or rivaroxaban individually, were associated with a reduced risk of the composite outcome in elderly patients with concurrent AF and dementia.

The Efficacy and Safety of DOACs in Inherited Antithrombin Deficiency: A Cohort Study from a Tertiary Referral Center.

Individuals with inherited antithrombin deficiency (IATD) have a high risk of venous thromboembolism (VTE). Most VTEs are managed with direct oral anticoagulants (DOACs), but the utility of DOACs in antithrombin deficiency (ATD) is unreported. Patients with IATD treated with DOAC were identified from our institutions' IATD registry. We assessed patients' characteristics, ATD type, and initial VTE characteristics, thrombosis recurrence and bleeding rates. Thirty-three patients received DOACs for 73 (38.5-111.5) months (median (interquartile range)). Prior to taking DOACs, 12 (36%) patients had VTE recurrence: these occurred after anticoagulation was ceased (4), nonadherence to VKA prior to DOAC use (3), or during heparin use in pregnancy (5). There were no VTE recurrences on standard-dose DOAC, except in a noncompliant patient receiving dabigatran. There was one recurrence with compliant DOAC use-a patient receiving rivaroxaban 10 mg. Six (18%) patients experienced clinically relevant bleeding, which was predominantly menorrhagia (5/6). One major bleeding event, intracranial hemorrhage, occurred in a patient receiving full-dose rivaroxaban who had refractory hypertension (0.5 events/100 patient-years). In this cohort, compliant DOAC users had an overall VTE recurrence rate of 0.5/100 patient-years, whereas with low-dose DOACs the event rate was 3.5/100 patient-years. Standard-dose DOACs appear efficacious and relatively safe in IATD.

Direct Oral Anticoagulants in Older and Frail Patients with Atrial Fibrillation: A Decade of Experience.

Both the prevalence of atrial fibrillation (AF) and its subsequent use of direct oral anticoagulants (DOACs) are rapidly increasing in patients of older age. In the absence of contra-indications, guidelines advocate anticoagulation based on the CHA2DS2-VASc score for all AF patients aged 75 and above. However, some practitioners are hesitant to prescribe anticoagulants to older and frail patients due to perceived elevated bleeding risks. This review delves into the comparative treatment outcomes of DOACs versus vitamin K antagonists (VKAs) in older patients with AF, particularly focusing on those of advanced age, frailty, increased risk of falling, chronic kidney disease (CKD), or with a history of major bleeding. Additionally, considerations on the use of off-label DOAC doses, the role of left atrial appendage (LAA) closure and future developments in factor XIa-inhibitors will be discussed. While strong evidence supports the use of DOACs in the vital older patients with nonvalvular AF, it remains scant in frail patient groups. There is some evidence from non-randomized studies suggesting that the effect of DOACs compared with VKAs is consistent between frail and nonfrail patients. However, recent findings from a single randomized trial showed increased bleeding risks but comparable thromboembolic outcomes in frail individuals switching from VKAs to DOACs. In patients with an increased risk of falling, data suggest no relevant interaction of increased risk of falling on the effectiveness and safety of DOACs compared with warfarin. Resuming oral anticoagulants in patients with Af after major bleeding seems to be beneficial. Off-label low-dose DOAC is often prescribed to patients who were underrepresented in larger randomized trails because of an elevated risk of bleeding or overexposure to DOACs, but its effect on clinical outcomes remains uncertain. DOACs are the recommended oral anticoagulant for vital older patients with AF. The scarcity of data backing DOAC use in frail individuals, those with renal impairments, or significant bleeding history underscores the necessity for further investigation. However, existing evidence suggests at least similar effectiveness and safety and potential benefits for DOACs in these patient subsets. Therefore, there is no reason to suggest these patients should be treated differently than the established guidelines regarding anticoagulation.

Direct oral anticoagulants in embolic stroke of undetermined source: an updated meta-analysis.

The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84-1.09; p = 0.50; I2 = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I2 = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I2 = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I2 = 0%). DOACs increased the risk of clinically relevant non-major bleeding(CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I2 = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87-2.83; p = 0.14; I2 = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67-1.42; p = 0.90; I2 = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I2 = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I2 = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin.

Efficacy and safety of direct oral anticoagulants versus warfarin in the treatment of cerebral venous sinus thrombosis.

Given the evolving application and promising outcomes of direct oral anticoagulants (DOACs) in various thromboembolic conditions, we aimed to compare the efficacy and safety of DOACs with warfarin in the post-acute treatment of cerebral venous sinus thrombosis (CVST) using clinical and radiological parameters. A total of 140 CVST patients were enrolled, with 95 receiving warfarin and 45 receiving DOACs as post-acute treatment. Clinical and imaging parameters of the patients in follow-up visits were investigated, including the last modified Rankin Scale (mRS), venousthromboembolic events, CVST recurrence, mortality rate, recanalization status, and hemorrhagic events, to compare the efficacy and safety of treatment between the two groups. At baseline, patients' assessments using two prognostic scores, ISCVT-RS and IN-REvASC, revealed that there was no statistically significant difference in the distribution of prognostic risk categories between the warfarin and DOACs groups. Following acute therapy, patients in the warfarin and DOACs groups were followedup forthemedian of359 and325days, respectively. Analysis to compare the efficacy of warfarin and DOACs revealed no significant difference in last mRS scores, CVST recurrencerate, venousthromboembolic events, and recanalizationstatus between the two groups. Additionally, there was no statistically significant difference in the risk of hemorrhagic events between warfarin and DOACsgroups. Our findings show that DOACs have comparable safety and efficacy in the post-acute treatment of CVST patients; however, large-scalerandomized controlled trials are required to validate our findings.

Efficacy and Safety of Direct Oral Anticoagulants versus Warfarin in Obese Patients (BMI ≥ 30 kg/m2) with Atrial Fibrillation or Venous Thromboembolism: An Updated Systematic Review and Meta-Analysis.

Background: Real-world data show limited utilization of direct oral anticoagulants (DOACs) in obese patients (body mass index [BMI] ≥ 30 kg/m2) due to concerns regarding their efficacy and safety in this demographic. Aim: This review aimed to consolidate current evidence on the efficacy and safety of DOACs versus warfarin in obese patients with non-valvular atrial fibrillation (AF) or venous thromboembolism (VTE). The primary efficacy outcome assessed a composite of all-cause mortality, stroke, systemic embolism (SE), and myocardial infarction (MI). Methods: A systematic search was conducted in MEDLINE, SCOPUS, and Cochrane databases from inception to December 28, 2023. Data were synthesized using random-effects meta-analysis. Results: A total of 35 studies involving 434,320 participants were analyzed. DOAC use was associated with a significant reduction in the risk of the composite outcome (RR = 0.80, 95% CI [0.65, 0.98], I2 = 95%), hemorrhagic stroke (RR = 0.58, 95% CI [0.38, 0.88], I2 = 92%), major bleeding (RR = 0.76, 95% CI [0.63, 0.92], I2 = 94%), gastrointestinal bleeding (RR = 0.59, 95% CI [0.49, 0.72], I2 = 88%), and intracranial bleeding (RR = 0.45, 95% CI [0.34, 0.60], I2 = 44%) compared to warfarin. A non-significant benefit of DOACs was observed for all-cause mortality, MI, the composite of stroke or SE, ischemic stroke, SE, VTE, and minor bleeding compared to warfarin. Subgroup analysis indicated no significant effect modification based on the indication for anticoagulation or study design. Conclusions: DOACs demonstrated a favorable efficacy and safety profile in obese individuals compared to warfarin.

Effectiveness of Direct Oral Anticoagulants and Vitamin K Antagonists in Preventing Stroke in Patients With Atrial Fibrillation and Liver Cirrhosis: A Systematic Review and Meta-Analysis.

Patients with atrial fibrillation and concurrent liver cirrhosis have been excluded from major clinical trials evaluating direct oral anticoagulants (DOACs) due to safety concerns. This has led to uncertainty regarding the optimal anticoagulant therapy in this population at high risk of thromboembolic events. We conducted a systematic review and meta-analysis to compare the effectiveness and safety of DOACs versus vitamin K antagonists (VKAs) in patients with atrial fibrillation and liver cirrhosis. Databases including Embase, MEDLINE/PubMed, and Web of Science were searched for relevant studies. The primary effectiveness outcome was stroke or systemic embolism, and the safety outcome was major bleeding events. A total of 10 studies were included in the meta-analysis. Compared to VKAs, the use of DOACs was associated with a significantly lower risk of stroke or systemic embolism (RR: 0.78, 95% CI: 0.65-0.92, p=0.005). The risk of all-cause mortality was comparable between the two groups (RR: 0.89, 95% CI: 0.74-1.07, p=0.23). Notably, DOACs demonstrated a significantly lower risk of major bleeding events (RR: 0.67, 95% CI: 0.61-0.73, p<0.01) compared to VKAs. This meta-analysis suggests that DOACs may be a favorable alternative to VKAs for the prevention of thromboembolic events in patients with atrial fibrillation and liver cirrhosis, with a lower risk of stroke or systemic embolism and major bleeding. However, further research is needed to establish optimal dosing strategies and assess the safety and efficacy of DOACs in patients with advanced liver disease.