Direct Oral Anticoagulants In Patients Research Articles

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.

Treatment appropriateness of direct oral anticoagulants in patients with atrial fibrillation for stroke prevention: A real-world prospective study.

Inappropriate use of direct oral anticoagulants (DOACs) is common, affecting up to 30% of atrial fibrillation (AF) population receiving treatment for stroke prevention. This study assessed appropriateness of anticoagulation in anticoagulation-naive AF patients treated with DOACs during a 12-month prospective follow-up. This prospective cohort study included all anticoagulation-naive AF patients referred for anticoagulation for stroke prevention at a tertiary cardiovascular center. Participants were prospectively followed through phone call interviews by a dedicated nurse at 1, 3, 6, 9, and 12 months after enrollment. Of 403 anticoagulation-naive AF patients, rivaroxaban was prescribed for 325 patients (80.7%) and apixaban for 78 (19.3%). Inappropriate therapy was observed in 23% (76/325) and 46% (36/78) of patients treated with rivaroxaban and apixaban, respectively. Undertreatment was predominant scenario for both drugs, detected in 78.5% (78/112) of patients treated inappropriately, and was more frequently observed with apixaban versus rivaroxaban (44.8% vs 16.3%). During 12 months, inappropriate treatment was corrected in only 13% of all patients. The multivariate regression model identified creatinine clearance ≤ 49 mL/min (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.12 to 4.21), female sex (OR, 1.81; 95% CI, 1.11 to 2.97), and age ≥ 80 years (OR, 1.85; 95% CI, 1.22 to 2.83) as independent covariates associated with inappropriate dosing. Inappropriate therapy with DOACs for stroke prevention in patients with AF is common, and the dosage were corrected in few patients during the 12-month follow-up. Our findings highlight the persistent lack of knowledge regarding appropriate DOAC dosage and need for continuous education.

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.

Real-world data on direct oral anticoagulants in BCR::ABL1-negative myeloproliferative neoplasms (MPNs): a multicenter retrospective study on behalf of scientific subcommittee on MPNs for Turkish society of hematology.

BCR::ABL1-negative myeloproliferative neoplasms (MPNs) pose a substantial risk of thrombosis, leading to significant morbidity and mortality. Anticoagulant therapy, historically based on vitamin K antagonists (VKAs), has limitations in preventing recurrent thrombotic events and managing bleeding complications. Direct oral anticoagulants (DOACs) offer a potential alternative with improved pharmacokinetics and compliance. However, evidence on DOAC efficacy and safety in MPNs remains limited, necessitating further investigation. In this multicenter retrospective study in Türkiye, we assessed real-world usage patterns and outcomes of DOACs in MPN patients. Data from 220 patients with PV, ET, or PMF receiving DOACs or VKAs for thrombosis or nonvalvular atrial fibrillation (NVAF) were collected from medical records. Thrombotic events and bleeding episodes were documented based on ISTH criteria. DOACs were used in 126 patients as first-line anticoagulant therapy or following VKAs. Ninety-four patients were on VKAs, of which 83 as a first-line treatment. There were eight thromboses (6.3%) seen in 126 DOAC patients, and similarly, seven episodes (9.4%) of thrombosis were observed in 94 patients using VKA. Major bleeding occurred in seven patients (5.6%) on DOAC and 3 (3.2%) in VKA. Thrombotic and bleeding risks were comparable between DOACs and VKAs (p = 0.708 and p = 0.158, respectively). The incidence rate of thrombosis in the VKA group is 1.1% and in the DOAC group is 1.9%. The incidence of major bleeding in the VKA group is 0.6% and 1.6% in the DOAC group. To the best of our knowledge, our study included the largest number of MPN patients to date, comparing DOACs with VKA in terms of both efficacy and safety, which suggests DOACs as promising alternatives to VKAs for managing thrombotic risk in MPNs with manageable toxicity. Despite the limitations of retrospective studies, DOACs' benefits in terms of efficacy and compliance warrant further investigation through prospective trials. Individualized treatment decisions should consider patient-specific factors, emphasizing collaborative efforts between specialists to optimize DOAC therapy in patients with MPNs. Comparable efficacy and safety between DOACs and VKAs were observed in MPN patients.

Predictors and Outcomes of Inappropriate Dosing of Direct Oral Anticoagulants in Patients Receiving Transcatheter Aortic Valve Implantation.

Direct oral anticoagulant (DOAC) dose adjustment is based on age, renal function, and body weight. There is a paucity of data describing the factors associated with the prescription of inappropriate dosage and their impact on clinical outcomes among patients receiving transcatheter aortic valve implantation (TAVI). In a single-center study, 432 patients who were on long-term DOAC therapy and underwent TAVI between 2015 and 2022 were included. We analyzed the predictors and outcomes of inappropriate dosing of DOACs; namely apixaban, dabigatran, edoxaban, and rivaroxaban. A composite endpoint, including all-cause mortality, life-threatening/major bleeding, stroke, peripheral thromboembolic complications, or myocardial infarction, was assessed after 1 year. In this TAVI cohort, inappropriate DOAC dosing was observed in 20.6% of patients. Inappropriate DOAC dosage was related to female gender (adj. odds ratio [OR] 2.72, 95% confidence interval [CI] 1.64-4.51, p < 0.001) as well as lower estimated glomerular filtration rate (eGFR) (adj. OR 0.99, 95% CI 0.98-1.00, p = 0.019), and to the administration of non-rivaroxaban DOACs (adj. OR 0.28, 95% CI 0.16-0.50, p < 0.001). After 1 year, patients on both appropriate and inappropriate DOAC dosage exhibited comparable rates of the composite endpoint (OR 0.88, 95% CI 0.53-1.46, p = 0.622). Old age (adj. OR 1.05, 95% CI 1.01-1.10, p = 0.018) as well as anemia (adj. OR 0.86, 95% CI 0.75-0.99, p = 0.031) emerged as independent predictors of the composite endpoint. In this TAVI cohort, female gender and renal insufficiency were associated with inappropriate DOAC dosage, whereas rivaroxaban was linked to appropriate dosing. Inadequate DOAC dosage did not translate into a worse outcome in our TAVI population. Prospective Segeberg TAVI Registry (ClinicalTrials.gov identifier: NCT03192774).

Clinical Features, Management, and Recurrence of Acute Ischemic Stroke Occurring in Patients on Oral Anticoagulant Treatment for Nonvalvular Atrial Fibrillation: A Real-World Retrospective Study.

The optimal management of acute ischemic stroke (AIS) in patients with oral anticoagulation (OA) is challenging. Our study aimed to analyze the clinical characteristics and outcome of AIS in patients with OA for nonvalvular atrial fibrillation (NVAF). We retrospectively analyzed data on NVAF patients with AIS on direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA) admitted to our Stroke Unit from 2017 to 2022. Ninety-day modified Rankin Scale (mRS), 90-day, and 12-month stroke recurrences were recorded. A total of 169 patients (53.2% female, mean age 82.8±6.7 y), 117 (69.2%) on DOAC, and 52 on VKA (30.8%), were enrolled. Mean age, in-hospital mortality, and 90-day mRS ≥4 were significantly higher in VKA patients. 63.4% of VKA patients had subtherapeutic INR, whereas 47.1% of DOAC patients were on low-dose (14.2% off-label). Large vessel occlusion and embolic etiology were more frequent in VKA patients (34.6% vs. 26.4%, P =0.358; 92.3% vs. 74.3%, P =0.007, respectively), whereas lacunar strokes were more frequent in DOAC patients (19.8% vs. 12.2%, P =0.366). Among patients on VKA before AIS 86.4% were switched to DOAC, whereas a DOAC-to-VKA and a DOAC-to-DOAC switch were done in 25.4% and 11.7%, respectively. Stroke recurrence occurred in 6.4% of patients at 90 days and 10.7% at 12 months. Anticoagulant switching was not associated with stroke recurrences. In our study, nonembolic etiology was more frequent in DOAC patients and anticoagulant switching did not reduce the risk of stroke recurrence. Prospective multicentric studies are warranted.

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.

10-Year Trends of Antithrombotic Therapy Status and Clinical Outcomes in Patients With Atrial Fibrillation and Renal Dysfunction - The Fushimi AF Registry.

Anticoagulation therapy for atrial fibrillation (AF) has undergone major changes following the introduction of direct oral anticoagulants (DOAC) in 2011. However, the transition of anticoagulation therapy for AF patients with severe renal dysfunction remains to be elucidated. Follow-up data, including creatinine clearance (CrCl), were available for 3,706 patients in the Fushimi AF Registry. We divided patients into 3 groups based on CrCl as follows: (1) CrCl ≥50 mL/min; (2) 50 mL/min>CrCl≥30 mL/min; and (3) CrCl <30 mL/min. In patients with CrCl ≥50 mL/min and 50>CrCl≥30 mL/min, prescription of oral anticoagulants increased year-by-year from 2011 to 2021 with a growing proportion of DOAC; however, the prescription of oral anticoagulants remained almost unchanged in those with CrCl <30 mL/min. In patients with CrCl ≥50 mL/min and 50 mL/min>CrCl≥30 mL/min, the incidence of adverse events, including stroke/systemic embolism and major bleeding, was lower among patients enrolled after 2014 than before 2013. However, these trends were not seen in patients with CrCl <30 mL/min. Despite the increased use of DOAC in patients with AF since 2011, anticoagulation therapy for AF patients with severe renal dysfunction has largely remained unchanged, and a reduction in adverse events in those patients has not been observed.

Application of DOAC Score for the risk-stratification of major bleeding in patients with venous thromboembolism on direct oral anticoagulants: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction Bleeding complications are still a major concern in anticoagulation therapy for venous thromboembolism (VTE), even in the direct oral anticoagulant (DOAC) era. Thus, the risk stratification of bleeding during anticoagulation therapy is essential, although most of currently available bleeding risk scores have been developed from patients receiving vitamin K antagonists, which could have limited validity in those receiving DOACs. Very recently, the DOAC Score has been developed to predict major bleeding in patients with atrial fibrillation on DOACs; however, the score has not yet been validated in patients with VTE. Purpose The present study aimed to evaluate the usefulness of the DOAC Score in patients with VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 3539 patients with VTE who received DOACs and had a calculated DOAC Score. The eligible patients were classified into 5 risk categories: very low (score 0–3), low (score 4–5), moderate (6–7), high (score 8–9), and very high (score ≥10). We used the Kaplan-Meier method to estimate the cumulative incidence and assessed the discriminatory ability of the DOAC Score for major bleeding at 1 year by calculating the area under the receiver operating characteristic curve. We also assessed the discriminatory ability of the VTE-BLEED and RIETE scores. Results In the present study population, the very low-risk group accounted for 1437 patients (41%), low-risk group for 828 (23%), moderate-risk group for 812 (23%), high-risk group for 326 (9.2%), and very high-risk group for 136 (3.8%). The proportion of anemia was highest in the very high-risk group (71%) and lowest in the very low-risk group (47%). The prevalence of active cancer was highest in the low-risk group (36%) and lowest in the very high-risk group (18%). During the first year of anticoagulation therapy, major bleeding occurred in 180 patients. The cumulative 1-year incidence of major bleeding seemed to be different according to the 5 groups, but the risks could not be well-stratified (Figure 1). The discriminating power of the DOAC Score was relatively low with a C-statistic of 0.52 (95% CI, 0.48–0.57) (Figure 2), while those of VTE-BLEED and RIETE scores were modest with C-statistics of 0.66 (95% CI, 0.60–0.73) and 0.67 (95% CI, 0.64–0.71), respectively. Conclusions The risk of 1-year major bleeding on DOACs in patients with VTE was not well-stratified according to the risk categories by the DOAC Score, which might suggest that patients with VTE have different risk factors for bleeding on DOACs as compared to those with atrial fibrillation. A new bleeding risk score for DOAC specifically in patients with VTE would be warranted in the future.Figure 1Figure 2

Inappropriate dosing of direct oral anticoagulants in patients with atrial fibrillation undergoing percutaneous coronary intervention

Abstract Background Underdose (inappropriate low-dose) of direct oral anticoagulants (DOAC) is sometimes prescribed due to concerns of bleeding risk in patients with atrial fibrillation (AF). In AF patients with coronary artery disease requiring percutaneous coronary intervention (PCI), careful treatment is required to prevent bleeding events because of intensive antithrombotic therapy with a combination of oral anticoagulants and antiplatelet agents. Purpose The purpose of this study was to investigate the prevalence of underdose of DOAC and its impact on clinical outcomes in AF patients with coronary artery disease undergoing PCI. Methods This multicenter observational cohort study enrolled patients with AF on DOAC undergoing PCI between January 2015 and March 2021 at 15 institutions. Appropriateness of DOAC dose was determined according to the manufacturer's labeling recommendations in Japan. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE), all-cause mortality, ischemic stroke, and major bleeding events, were evaluated. Results Of 630 patients enrolled, 168 patients (26.7%) received underdose, 227 (36.0%) received appropriate low-dose, 213 (33.8%) received appropriate standard-dose, and 22 (3.5%) received overdose. Because of the extremely small number of patients in the overdose group, the primary analysis of the present study was a comparison between the underdose group (n=168) and the appropriate dose group (appropriate low-dose and standard-dose groups) (n=440). Although the incidence of MACE, all-cause mortality, and major bleeding events was not significantly different between the 2 groups (log-rank p=0.872, p=0.170, and p=0.725), ischemic stroke more frequently occurred in the underdose group compared with the appropriate dose group (log-rank p=0.010) (Figure 1). The multivariable Cox regression analysis determined underdose of DOAC as an independent predictor for ischemic stroke (adjusted HR 3.288, 95% CI: 1.189-9.088, p=0.022). Conclusions Compared with appropriate dose of DOAC, underdose was associated with a higher incidence of ischemic stroke, despite no significant difference in MACE, all-cause mortality, and major bleeding events, in AF patients undergoing PCI.Figure 1

Comparison of interrupted and uninterrupted anticoagulation strategies for cardiac implantable electronic device insertion: a systematic review and meta-analysis

Abstract Introduction Up to 35% of patients who are candidates for a cardiac implantable electronic device (CIED) receive chronic anticoagulation. However, guidelines on anticoagulant management in the perioperative period of CIED insertion differ worldwide. It is uncertain whether interrupting or continuing anticoagulation in these settings provides optimal outcomes. Purpose To assess the effects of interrupting versus continuing chronic anticoagulation with either warfarin or a direct oral anticoagulant (DOAC) in the perioperative setting of CIED insertion. Methods CENTRAL, MEDLINE, Embase, Web of Science, and two trial registries were searched from inception to 26 November 2021. Randomised controlled trials (RCTs) assessing interrupting chronic warfarin or DOAC therapy, with or without heparin bridging, versus continuing anticoagulation in adults undergoing CIED insertion were included. Comparisons were divided into two categories: interrupted versus uninterrupted warfarin and interrupted versus uninterrupted DOAC. Outcomes were expressed as risk ratios (RR) with 95% confidence intervals (95%CI). Inverse variance random-effects models were used for the meta-analyses. Risk of bias (RoB) was assessed using the Cochrane RoB2 tool, and certainty of evidence (CoE) per outcome was assessed with GRADE methods. Results Ten RCTs (n=2221) were included: five RCTs (n=1267) used warfarin; four RCTs (n=954) used DOACs. One additional RCT using warfarin was ongoing without any outcome data available. Bleeding events included device-pocket haematoma, haemothorax, cardiac tamponade, and non-tamponade pericardial effusion. Interrupted versus uninterrupted warfarin: The evidence is very uncertain on the effect of interrupted warfarin on device-pocket haematoma (RR 1.89, 95%CI 0.85 to 4.20, 5 RCTs, very low CoE) and bleeding events (RR 1.94, 95%CI 0.86 to 4.41, 5 RCTs, very low CoE). Interrupted warfarin may result in little to no difference in thromboembolic events (RR 0.85, 95%CI 0.18 to 4.11, 5 RCTs, low CoE) and ischaemic stroke (RR 1.01, 95%CI 0.11 to 9.61, 2 RCTs, low CoE). Interrupted warfarin may reduce all-cause mortality (RR 0.35, 95%CI 0.04 to 2.93, 3 RCTs, low CoE). Interrupted versus uninterrupted DOAC: The evidence is very uncertain on the effect of interrupted DOAC on device-pocket haematoma (RR 1.15, 95%CI 0.58 to 2.28, 4 RCTs, very low CoE) and bleeding events (RR 1.14, 95%CI 0.58 to 2.21, 4 RCTs, very low CoE). Interrupted DOAC may result in little to no difference in thromboembolic events (RR 0.98, 95%CI 0.06 to 15.63, 3 RCT, low CoE) and ischaemic stroke (RR 0.98, 95%CI 0.06 to 15.63, 2 RCTs, low CoE). Interrupted DOAC may reduce all-cause mortality slightly (RR 0.49, 95% CI 0.04 to 5.39, 2 RCTs, low CoE). Conclusion Interrupting anticoagulation with either warfarin or DOACs in patients undergoing CIED insertion produced similar outcomes as uninterrupted anticoagulation.Figure 1.Figure 2.

Cost differences between oral anticoagulation therapies in atrial fibrillation patients

Abstract Background Direct oral anticoagulants (DOACs) have largely replaced warfarin as the primary choice of oral anticoagulation (OAC) in atrial fibrillation (AF) patients. This study uses a nationwide registry data set to compare the health and social care costs of AF patients using different OAC therapies. We studied how these costs were distributed among different care services in the year following AF onset and how the costs develop in time before and after AF diagnosis. Methods This study is a part of the Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) research project, which includes data on patients with AF, combining registry data on primary and secondary care services as well as social services, drug purchases and laboratory data. We included all new-onset AF patients from 2011 to 2017 in Finland with an indication for OAC treatment. Patients were divided based on their first OAC purchase. Time in therapeutic range (TTR) values were assessed for warfarin patients, and they were divided into quartiles based on their TTR value. Standardized costs were determined for different health and social care contacts, accounting for hospital care, primary and ambulatory care, and long-term care. Drug costs were acquired from the Reimbursement for Prescription Medicines registry. Results A total of 130,745 patients (66,610 on warfarin, 32,996 on DOACs) were included. First-year total costs after onset of AF were €10,412 for rivaroxaban (n=13,320), €12,631 for apixaban (n=11,886), €10,706 for dabigatran (n=7,514) and €10,689 for edoxaban (n=366). Costs of care clustered near the diagnosis of AF (Figure 1). Costs for warfarin patients increased inversely with TTR, ranging from €10,945 in the highest TTR quartile (TTR over 82%) to €21,387 in the lowest (TTR under 57%). Average first-year costs for warfarin patients were €15,689, higher than DOAC patients by €3,058-€5,277 (Figure 2). Patients without any OAC had the highest first-year costs, €17,898. Patients with high risk of stroke had higher total costs both in patients using DOACS (€7,271 for patients with a CHA2DS2VA score of 1 vs €11,947 for patients with CHA2DS2VA 2+) and warfarin (€9,933 for CHA2DS2VA 1 vs €16,354 for CHA2DS2VA 2+). Drug costs averaged €1,541 for rivaroxaban, €1,659 for apixaban, €1,495 for dabigatran and €1,540 for edoxaban, and €986 warfarin users. Hospital care was the largest cost driver with 64% of total costs across the whole cohort, followed by primary care (19%), drug purchases (7%), social service costs (6%) and reimbursements for travel and private care (4%). Conclusions DOACs were superior to warfarin in a broad range of social and healthcare cost measures despite higher drug expenses. Patients on warfarin with low TTR and patients without any OAC had the highest cost of care.

Bilateral Adrenal Hemorrhage in a Patient Anticoagulated with Apixaban for Antiphospholipid Syndrome (APS): A Rare Case Report

Context: Adrenal hemorrhage is a recognized yet rare complication associated with antiphospholipid syndrome (APS), an autoimmune disorder characterized by the presence of antiphospholipid antibodies that increase the risk of thrombosis. The incidence of adrenal hemorrhage in patients with APS has a diagnostic yield of approximately one-third, indicating that it may often go unrecognized in clinical practice. Traditionally, the management of APS has relied on anti-vitamin K therapy, such as warfarin. However, the advent of direct oral anticoagulants (DOACs) has prompted discussions about their use as an alternative. Recent clinical guidelines, however, strongly advise against the use of DOACs in patients with APS due to concerns over their safety and efficacy in preventing thromboembolic events. Case Presentation: This case study describes a 53-year-old woman with a history of venous thromboembolism who was treated with apixaban, a direct oral anticoagulant. She presented with acute abdominal pain and symptoms suggestive of adrenal insufficiency. Initial evaluations revealed significant changes in her clinical condition, leading to further diagnostic imaging. A CT scan demonstrated bilateral adrenal hemorrhage, which was a surprising finding given her anticoagulation therapy. Subsequent laboratory tests indicated a positive triple antibody profile, confirming a diagnosis of primary antiphospholipid syndrome. This case is particularly noteworthy as there have been limited documented instances of adrenal hemorrhage in patients receiving chronic anticoagulation with apixaban. The presentation of bilateral adrenal hemorrhage in the context of APS adds a crucial dimension to the understanding of the disease and its management. Conclusion: This case highlights the potential for serious complications, such as adrenal hemorrhage, in patients with antiphospholipid syndrome, particularly those treated with direct oral anticoagulants. It underscores the necessity for clinicians to remain vigilant for such rare yet significant events in the management of APS. Additionally, this case raises important questions regarding the appropriateness of DOACs in this patient population, especially given the latest recommendations against their use. Increased awareness and further investigation into the implications of anticoagulation strategies in APS patients are warranted to improve patient outcomes and safety.

Commentary on the ANNEXA-I trial from the guideline group of the European Society of Anaesthesiology and Intensive Care (ESAIC) on the reversal of direct oral anticoagulants in patients with life threatening bleeding.

Commentary on the ANNEXA-I trial from the guideline group of the European Society of Anaesthesiology and Intensive Care (ESAIC) on the reversal of direct oral anticoagulants in patients with life threatening bleeding.

Revisiting Left Atrial Appendage Closure Versus Oral Anticoagulants in Recurrent Atrial Fibrillation Management: An Updated Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is a significant public health problem due to its association with coronary heart disease, stroke, and mortality, especially in the elderly. Therefore, traditional warfarin therapy, direct oral anticoagulants (DOACs), and the recent left atrial appendage closure (LAAC) have been compared as treatment approaches. In this regard, we aimed to synthesize the current evidence regarding the comparison these mentioned modalities in patients with AF. A comprehensive database search for records comparing LAAC and DOACs in patients with AF was conducted until December 15, 2023. An updated meta-analysis was conducted using fixed and random effect models to calculate odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CIs) for dichotomous and continuous outcomes, respectively. Eleven studies were eligible that included a total of 68171 patients. Compared to DOACs, the LAAC group had a lower rate of hospital stay duration (MD -1.23; 95% CI -1.51 to -0.95;p< 0.001). There was no statistically significant difference between LAAC and DOACs in terms of the composite outcome of stroke, systemic embolism, cardiovascular death, all-cause mortality, ischemic stroke and thromboembolic events ischemic, major bleeding and cardiovascular mortality (OR 0.83, 95% CI 0.27-2.48,P= 0.73).Our meta-analysis showed a lower rate of hospital stay duration that favors LAAC. However, the risk of composite outcomes of stroke, systemic embolism, cardiovascular death, all-cause mortality, ischemic stroke, thromboembolic events, ischemic stroke, major bleeding, and cardiovascular mortality was similar between the two treatment groups.

Comparative Safety and Effectiveness of Heparin vs. Direct Oral Anticoagulants in Patients with Cirrhosis and ESKD

Comparative Safety and Effectiveness of Heparin vs. Direct Oral Anticoagulants in Patients with Cirrhosis and ESKD

A new strategy for monitoring of direct oral anticoagulants in patients with cyanotic and complex congenital heart disease

BackgroundPatients with congenital heart disease (CHD) often require an oral anticoagulation. Vitamin K antagonists (VKA) are the standard treatment, however, an increased hematocrit in patients with secondary erythrocytosis due to cyanosis complicates the correct measurement of the international normalized ratio. Direct oral anticoagulants (DOAC) could be an alternative, but data on their efficacy and safety in complex and cyanotic CHD patients are scarce. This study proposes a new strategy of DOAC monitoring in these patients using D-dimers and DOAC trough levels. MethodsThis is a retrospective study including cyanotic and complex CHD patients requiring oral anticoagulation. Clinical, cardiac imaging and laboratory data were collected before and after start of DOAC. The new monitoring strategy consists of determination of D-dimers and DOAC trough levels at 1–4 weeks, 1–6 months, 6–12 months, >1 year after start of DOAC. ResultsEleven patients were included. For 10 patients D-dimers and DOAC trough levels were in target range. In one patient, D-dimers increased continuously after start of DOAC despite dose escalation, suggesting insufficient DOAC efficacy and finally requiring a switch to VKA. D-dimers subsequently decreased under VKA to the therapeutic range. In three patients, one thromboembolic and two minor bleeding complications occurred. No major complications were observed. ConclusionsWe propose a new strategy of monitoring of oral anticoagulation with DOAC and report its implementation in clinical routine. Highlighting the importance of pharmacokinetic and -dynamic monitoring, this strategy could improve safety and efficacy of DOAC in cyanotic and complex CHD which, however, requires a prospective validation.

The effect of early surgery on clinical outcomes in proximal femoral fracture patients receiving chronic anticoagulation: A japanese nationwide database study

Introduction: Surgery is often delayed in patients with proximal femoral fractures who receive oral anticoagulants, to avoid complications related to perioperative bleeding. However, surgery delay may increase the risk of postoperative mortality. Our primary goal was to understand whether anticoagulated patients benefit from early surgery in terms of survival and perioperative complications.Methods: This is a multicenter retrospective cohort study of 581,189 patients with proximal femoral fractures. About 2.0 % (n = 11,385) received direct oral anticoagulants (DOAC) and 1.5 % (n = 8,726) received warfarin. Surgery was performed within 48 h in 37.6 % of DOAC patients, 27.6 % of warfarin patients and in 41.9 % of nonanticoagulated patients. Survival analysis was applied to compare mortality rate, blood transfusions, systemic complications and surgical complications during hospitalization between the study groups.Results: Patients receiving anticoagulation were older and had more comorbidities than patients without anticoagulation. There were overall similar rates of mortality (0.8 %, 1.1 % and 1.2 %) and surgical complications (2.1 %, 2.1 % and 2.2 %) in non-anticoagulated, DOAC and warfarin patients. Blood transfusions and systemic complications were higher in all anticoagulated patients regardless of surgery timing. There were comparable rates of early surgery (41.9 %, 37.6 % and 27.6 %, respectively). When operated early, DOAC patients had more surgical complications (OR=1.24, p = 0.04). Warfarin patients operated early had higher mortality (OR=1.48, p = 0.08) and higher risk of blood transfusions (OR=1.24, p < 0.001).Discussion: Age and comorbidities could explain higher rates of postoperative systemic complications in anticoagulated patients. Nevertheless, overall short-term mortality was similar between the groups. Early surgery was associated with higher rates of surgical complications in DOAC patients. When operated early, patients receiving warfarin were at an increased risk of mortality (p = 0.08) and perioperative blood transfusions.

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.

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.