Direct Oral Anticoagulants Group Research Articles

Safety and Efficacy of Direct Oral Anticoagulants vs Warfarin in Patients With Obesity and Venous Thromboembolism: A Retrospective Analysis.

Current venous thromboembolism guidelines recommend using direct oral anticoagulants (DOACs) over warfarin regardless of obesity status; however, evidence remains limited for the safety and efficacy of DOAC use in patients with obesity. This retrospective analysis sought to demonstrate the safety and efficacy of DOACs compared with warfarin in a diverse population of patients with obesity in light of current prescribing practices. A retrospective cohort study was conducted at a large academic health system between July 2014 and September 2019. Adults with an admission diagnosis of deep vein thrombosis (DVT) or pulmonary embolism, with weight greater than 120 kg or a body mass index greater than 40, and who were discharged on an oral anticoagulant were included. Outcomes included occurrence of a thromboembolic event (DVT, pulmonary embolism, or ischemic stroke), bleeding event requiring hospitalization, and all-cause mortality within 12 months following index admission. Out of 787 patients included, 520 were in the DOAC group and 267 were in the warfarin group. Within 12 months of index hospitalization, thromboembolic events occurred in 4.23% of patients in the DOAC group vs 7.12% of patients in the warfarin group (hazard ratio, 0.6 [95% CI, 0.32-1.1]; P = .082). Bleeding events requiring hospitalization occurred in 8.85% of DOAC patients vs 10.1% of warfarin patients (hazard ratio, 0.93 [95% CI, 0.57-1.5]; P = .82). A DVT occurred in 1.7% and 4.9% of patients in the DOAC and warfarin groups, respectively (hazard ratio, 0.35 [95% CI, 0.15-0.84]; P = .046). No significant differences could be determined between DOACs and warfarin for cumulative thromboembolic or bleeding events, pulmonary embolism, ischemic stroke, or all-cause mortality. The risk of DVT was lower with apixaban and rivaroxaban. Regardless of patient weight or body mass index, physicians prescribed DOACs more commonly than warfarin.

Safety and efficacy of anticoagulation therapy post atrial fibrillation ablation

Abstract Funding Acknowledgements None. Background Thromboembolic complications can be life-threatening during atrial fibrillation (AF) catheter ablation. The aim of our single center, retrospective study was to evaluate the safety and efficacy of continuous treatment using direct oral anticoagulants (DOACs) as an alternative to uninterrupted acenocoumarol for periprocedural anticoagulation. Purpose To record the safety and efficacy of the oral anticoagulants post atrial fibrillation ablation. Methods We studied 1999 patients undergoing AF catheter ablation between June 2013 and December 2021 in our center. All patients were assigned to take acenocoumarol (group 1, 194 patients) or DOACs (group 2, 1805 patients) for ≥2 months before the procedure. We compared thromboembolic and bleeding complications between the 2 groups. Results Our analysis showed no significant difference in major and minor complications between the 2 patient groups with the exception of the occurrence of groin hematoma with a clear superiority of DOACs (2.06%-0.5%, p<0.05). Specifically, 4 of 194 patients (2.06%) using uninterrupted acenocoumarol had a major complication (3 patients [1.55%] had transient ischemic attack resolved 8 hours later and 1 [0.52%] had pericardial tamponade, and 7 patients (3.61%) had minor complications (4 [2.06%] groin hematoma and 3 [1.55%] mild pericardial efussion). In group 2, 14 of 1805 patients (0.78%) had a major complication (11 patients had transient ischemic attack (0.61%) and 3 patients (0.17%) had pericardial tamponade). In the same group, 31 patients (1.72%) had a minor complication (3 patients [0.17%] presented with pseudoaneurysm or femoral arteriovenous fistula between the femoral artery and femoral vein, 19 [1.05%] with pericardial effusion <1 cm, and 9 [0.5%] groin hematoma). Conclusions DOACs and acenocoumarol have similar safety and effectiveness regarding thromboembolic complications prevention without increasing bleeding complications with the exception of the occurrence of groin hematoma with a clear superiority of DOACs.

Risk of dentoalveolar surgery postoperative bleeding in patients taking direct oral anticoagulants and vitamin K antagonists: A prospective observational study

The aim of this study was to evaluate whether direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA) increase the risk of postoperative bleeding after dentoalveolar surgery. Patients were classified into two groups: one taking DOAC and the other taking VKA with a therapeutic INR range. The control group comprised non-anticoagulated subjects. Participants were matched regarding dentoalveolar procedure. The primary predictor was anticoagulant status. The primary outcome was postoperative bleeding. The DOAC group comprised 77 patients, while the VKA group and control group each consisted of 103 participants. In each group, 103 dentoalveolar surgical procedures were conducted. Postoperative bleeding was recorded in 3/103 (2.9%), 5/103 (4.8%), and 1/103 (0.97%) occasions in the DOAC, VKA, and control groups, respectively, without significant difference (χ2; p = 0.54). The fully adjusted odds ratio for postoperative bleeding was 0.14 (CI 0.01–1.61; p = 0.05) for patients taking DOAC and 0.19 (CI 0.02–1.65; p = 0.285) for those taking VKA compared with non-anticoagulated controls. In conclusion, there was no increase in risk for clinically significant postoperative bleeding after dentoalveolar surgery in patients taking DOAC or VKA compared with non-anticoagulated subjects. Dentoalveolar surgery in patients taking DOAC and VKA can be performed safely without therapy cessation.The study was registered at Clinicaltrials.gov (NCT04505475).

Safety and efficacy of direct oral anticoagulants in comparison to warfarin in obese patients with atrial fibrillation: A systematic review and meta-analysis.

Obesity affects nearly 650 million adults worldwide, and the prevalence is steadily rising. This condition has significant adverse effects on cardiovascular health, increasing the risk of hypertension, coronary artery disease, heart failure, and atrial fibrillation (AF).While anticoagulation for obese patients with AF is a well-established therapy for the prevention of thromboembolism, the safety and efficacy of different anticoagulants in this specific population are not well explored. This meta-analysis aimed to compare direct oral anticoagulants (DOAC)to vitamin K antagonists in obese populations with AF. The PRISMA guidelines were followed for this meta-analysis, registered in PROSPERO (CRD42023392711).PubMed, PubMed Central, Embase, Cochrane Library, and Scopus databases were searched for relevant articles from inception through January 2023. Two independent authors screened titles and abstracts, followed by a full-text review in Covidence. Data were extracted in Microsoft Excel and analyzed using RevMan v5.4 using odds ratio as an effect measure. Two thousand two hundred fifty-ninestudies were identified from the database search, and 18 were included in the analysis. There were statistically significant reductions in the odds of ischemic and hemorrhagic stroke in the DOAC group compared with the VKA group (OR0.70, CI 0.66-0.75) and (OR0.47, CI 0.35-0.62), respectively. In addition, the DOAC group exhibited lower odds of systemic embolism (OR0.67, CI 0.54-0.83), major bleeding (OR0.62, CI 0.54-0.72), and composite outcome (OR0.72, CI 0.63-0.81). Based on the findings from this meta-analysis, DOACs demonstrate superior safety and efficacy in obese patients with AF compared withVKAs. These results may have significant implications for guiding anticoagulation strategies in this patient population.

Preoperative Drug Monitoring in Management of Patients with Hip Fracture on Treatment with Direct Oral Anticoagulants.

Aim of the present study was to evaluate whether monitoring direct oral anticoagulant (DOAC) levels may improve management of anticoagulated patients who need surgery for hip fracture. A total of 147 out of 2231 (7.7%) patients with hip fracture admitted to a tertiary teaching hospital were on DOACs (group A), whereas 206 patients matched for age, sex, and type of fracture not on anticoagulant or P2Y12 platelet inhibitors were considered as control group (group B). Patients on DOACs were divided into two subgroups: A1 in which intervention was scheduled in relation to the last drug intake according to current guidelines, and A2 included patients in whom time of surgery (TTS) was defined according to DOAC levels. Neuraxial anesthesia was considered with DOAC levels <30 ng/mL, general anesthesia for levels in the range 30-50 ng/mL. TTS was significantly lower in controls than in DOAC patients: surgery within 48 hours was performed in 80.6% of group B versus 51% in group A (p<0.0001). In A2, 41 patients underwent surgery within 48 hours (56%) in comparison to 32 A1 patients (45.1%; p=0.03). TTS and length of hospitalization were on average 1 day lower in patients with assay of DOAC levels. Finally, 35/39 (89%) patients with DOAC levels <50 ng/mL had surgery within 48 hours (26 under neuraxial anesthesia, without any neurological complication, and 13 in general anesthesia). DOAC assay in patients with hip fracture may be useful for correct definition of time to surgery, particularly in patients who are candidates for neuraxial anesthesia. Two-thirds of patients with DOAC levels <50 ng/mL at 48 hours from last drug intake underwent uneventful neuraxial anesthesia, saving at least 24 hours in comparison to guidelines.

The effect of off-label use of reduced-dose direct oral anticoagulants therapy in the treatment of pulmonary embolism comparable to standard-dose therapy

Direct oral anticoagulants (DOACs) have been shown to be effective and safe in preventing pulmonary embolism recurrence. In this single-center retrospective observational study, we aimed to evaluate the efficacy and safety of reduced-dose DOACs in 86 consecutive patients with acute pulmonary embolism. Patients were divided into standard-dose and reduced-dose DOACs groups. Initial clot volume did not significantly differ between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 18.8 [Q1–Q3 7.3–30.8] mL vs. 10.0 [Q1–Q3 3.2–27.9] mL, p = 0.1). Follow-up computed tomography (CT) within 30 days showed a higher rate of clot volume reduction or disappearance in the standard-dose group compared to the reduced-dose group (standard-dose DOACs vs. reduced-dose DOACs, 81.6% vs. 53.9%, p = 0.02). However, at the final follow-up CT, there was no significant difference in clot volume change between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 91.5% vs. 82.0%, p = 0.19). Major bleeding occurred in two patients in the standard-dose group (4.3%) and three patients in the reduced-dose DOACs group (7.7%) (p = 0.5). In conclusion, while standard-dose DOACs demonstrated superior efficacy in early clot reduction, reduced doses of apixaban and edoxaban showed comparable efficacy and safety profiles in long-term treatment of acute pulmonary embolism in certain patients.

Abstract WP19: Is Direct Oral Anticoagulant More Effective Than Warfarin to Reduce Size of Left Atrial Thrombus in Stroke Patients?

Objective: The presence of left atrial thrombus (LAT) in acute stroke patients with nonvalvular atrial fibrillation (NVAF) is the major embolic source for recurrent stroke. The aim of this study was to investigate whether direct oral anticoagulants (DOAC) is more effective than warfarin to reduce the size of LAT detected in acute stroke patients with NVAF. Methods: Among acute stroke patients admitted to five major comprehensive stroke centers from January 2017 to December 2022, acute stroke patients with both AF and LAT detected by transesophageal echocardiography (TEE) were selected, and patients with follow-up evaluation were enrolled. All patients were treated with anticoagulation such as DOAC or warfarin for LAT. Thus, patients were classified into two groups according to the type of anticoagulation; the DOAC group and the warfarin group. We compared the clinical characteristics, the dissolution of LAT, and recurrent stroke within three months after stroke onset evaluated between the two groups. Results: 63 patients (median age 77, male 33 [52%]) were enrolled. DOAC and warfarin groups had 22 (35%) and 41(65%) patients, respectively. Age, gender, NIHSS scores on admission were not different between the two groups. Age was 77 years (IQR, 68-81) in the DOAC group and 76 years (IQR, 68-81) in the warfarin group (P=0.644). 10 men (46%) were in the DOAC group, and 23 (56%) were in the warfarin group (P=0.442). The NIHSS score at admission was 3 (IQR, 1-18) in the DOAC group and 4 (IQR, 2-14) in the warfarin group (P=0.393). Initial LAT size was 0.83 (IQR, 0.41-1.27) cm2 in DOAC and 0.88 (IQR, 0.40-1.56) cm2 in warfarin (p=0.48). On follow-up evaluation (10 [IQR, 7-15] days after initial TEE), the disappearance of LAT was more frequently seen in DOAC group than warfarin group (13/22 [59%] vs. 14/41 [34%], P=0.016). Recurrent stroke within three months after stroke was 1/22 (5%) in DOAC and 3/41 (7%) in warfarin (P=1.000), which was not different. Conclusion: In acute stroke patients with NVAF, DOAC should be more effective than warfarin to dissolve LAT detected by TEE.

Direct oral anticoagulants compared with warfarin in patients with left ventricular thrombus: a cohort study from China.

Current guidelines recommend vitamin K antagonist (VKA) for left ventricular (LV) thrombus. This study aimed to compare the effectiveness and safety of direct oral anticoagulant (DOAC) and warfarin in Chinese patients with LV thrombus. Patients with LV thrombus admitted to Beijing Anzhen Hospital of Capital Medical University between January 2018 and January 2022, were enrolled in this cohort study. The primary endpoint was defined as thrombus resolution within 90 days. The secondary endpoints included thrombus resolution within 180 days, major bleeding events, and minor bleeding events. All patients were followed up for at least 90 days after diagnosis of LV thrombus. Patients were divided into the VKA and DOAC groups according to the anticoagulants. Differences in clinical endpoint events between the two groups were compared. This study included 129 and 111 patients in the VKA and DOAC groups, respectively. After adjusting for gender and smoking status, no significant difference was observed in thrombus resolution within 90 days between the VKA and DOAC groups. Additionally, there was no difference between the two groups in the secondary endpoints of thrombus resolution within 180 days, major bleeding, and minor bleeding. In subgroup analysis, rivaroxaban and dabigatran did not show significant differences in primary and secondary endpoints. This study showed no significant difference in thrombus resolution between DOAC and warfarin. DOAC might be an alternative to warfarin for the treatment of LV thrombus. However, further large prospective studies are required to explore the efficacy and safety of DOAC in patients with LV thrombus.

Anticoagulant prescribing patterns in patients with primary central nervous system malignancies and secondary metastases.

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and stage 5 chronic kidney disease under dialysis: A systematic review and meta-analysis of randomized controlled trials.

In patients with atrial fibrillation (AF) and normal or slightly impaired renal function, the use of direct oral anticoagulants (DOACs) is preferable to vitamin K antagonists (VKAs). However, in patients undergoing hemodialysis, the efficacy, and safety of DOACs compared with VKAs are still unknown. To review current evidence about the safety and efficacy of DOACs compared to VKAs, in patients with AF and chronic kidney disease under hemodialysis. We systematically searched PubMed, Scopus, and Cochrane databases for RCTs comparing DOACs with VKAs for anticoagulation in patients with AF on dialysis therapy. Outcomes of interest were: (1) stroke; (2) major bleeding; (3) cardiovascular mortality; and (4) all-cause mortality. Statistical analysis was performed using RevMan 5.1.7 and heterogeneity was assessed by I2 statistics. Three randomized controlled trials were included, comprising a total of 383 patients. Of these, 218 received DOACs (130 received apixaban; 88 received rivaroxaban), and 165 were treated with VKAs (116 received warfarin; 49 received phenprocoumon). The incidence of stroke was significantly lower in patients treated with DOACs (4.7%) compared with those using VKAs (9.5%) (RR 0.42; 95% CI 0.18-0.97; p = 0.04; I2 = 0%). However, the difference was not statistically significant in the case of ischemic stroke specifically (RR 0.42; 95% CI 0.17-1.04; p = 0.06; I2 = 0%). As for the major bleeding outcome, the DOAC group (11%) had fewer events than the VKA group (13.9%) but without statistical significance (RR 0.75; 95% CI 0.45-1.28; p = 0.29; I2 = 0%). There was no significant difference between groups regarding cardiovascular mortality (RR 1.23; 95% CI 0.66-2.29; p = 0.52; I2 = 13%) and all-cause mortality (RR 0.98; 95% CI 0.77-1.24; p = 0.84; I2 = 16%). This meta-analysis suggests that in patients with AF on dialysis, the use of DOACs was associated with a significant reduction in stroke, and a numerical trend of less incidence of major bleeding compared with VKAs, but in this case with no statistical significance. Results may be limited by a small sample size or insufficient statistical power.

Renal function and periprocedural complications in patients undergoing left atrial catheter ablation: A comparison between uninterrupted direct oral anticoagulants and phenprocoumon administration.

Data regarding uninterrupted oral anticoagulation in patients with chronic kidney disease (CKD) during catheter ablation for left atrial arrhythmias is limited. This study aimed to evaluate the safety and efficacy of periprocedural uninterrupted direct oral anticoagulants (DOAC) compared with uninterrupted phenprocoumon in patients with CKD undergoing left atrial catheter ablation. We conducted a retrospective single-center study of patients who underwent left atrial catheter ablation between 2016 and 2019 with underlying chronic kidney disease (glomerular filtration rate (GFR) between 15 and 45ml/min). The primary objective of this study was to investigate whether direct oral anticoagulant (DOAC) therapy or warfarin presents a superior safety profile in patients with chronic kidney disease (CKD) undergoing left atrial catheter ablation. We compared periprocedural complications (arteriovenous fistula, aneurysm, significant hematoma (> 5cm)) and/or bleeding (drop in hemoglobin of >2g/dl, pericardial effusion, retroperitoneal bleeding, other bleeding, stroke) between patients receiving either uninterrupted DOAC or warfarin therapy. Secondary analysis included patient baseline characteristics as well as procedural data. A total of 188 patients (female n = 108 (57%), mean age 75.3 ± 8.1years, mean GFR 36.8 ± 6ml/min) were included in this study. Underlying arrhythmias were atrial fibrillation (n = 104, 55.3%) and atypical atrial flutter (n = 84, 44.7%). Of these, n = 132 patients (70%) were under a DOAC medication, and n = 56 (30%) were under phenprocoumon. Major groin complications including pseudoaneurysm and/or AV fistula occurred in 8.9% of patients in the phenprocoumon group vs. 11.3% of patients in the DOAC group, which was not statistically significant (p = 0.62). Incidence of cardiac tamponade (2.3% vs. 0%; p = 0.55) and stroke (0% vs. 0%) were low in both DOAC and phenprocoumon groups with similar post-procedural drops in hemoglobin levels (1.1±1g/dl vs 1.1±0.9g/dl; p= 0.71). The type of anticoagulation had no significant influence on bleeding or thromboembolic events as well as groin complications in this retrospective study. Despite observing an increased rate of groin complications, the uninterrupted use of DOAC or phenprocoumon during left atrial catheter ablation in patients with CKD appears to be feasible and effective.

Comparison of vitamin K and non-vitamin K oral anticoagulants and the bleeding frequency in the emergency department.

Safety studies of anticoagulant therapy have so far been conducted on many subjects in controlled conditions (i.e., clinically monitored) and demonstrated the noninferiority of new ones over old anticoagulant drugs. Data on the propositions for the presence of symptoms and signs of bleeding among various anticoagulants in the emergency department indicate that these data do not match the data published so far. The aim of the study was to investigate the differences in the frequency of bleeding and bleeding-related symptoms as a reason for emergency department attendance in patients on anticoagulant therapy. The study included patients from the emergency department of University Hospital for one year, who were on anticoagulant therapy and who met the inclusion criteria. Out of a total of 595 patients, 409 were on warfarin (68.74%), and the rest were taking direct oral anticoagulants (DOAC): dabigatran 71 (11.93%), rivaroxaban 66 (11.09%) and apixaban 49 (8.23%). Out of 409 patients taking warfarin, 34.4% were adequately anticoagulated with the frequency of bleeding 13.7%, while in 57.2% of patients, PT INR was higher than the reference values with the frequency of bleeding 15.0%. A comparison between all DOAC groups and adequately anticoagulated warfarin patients in the frequency of bleeding and bleeding-related symptoms as a reason for emergency attendance yielded a difference that was marginally statistically significant (Pearson Chi-Square = 7.554, p = 0.052). Monitoring the frequency of bleeding and bleeding-related symptoms in patients on oral anticoagulant therapy as a reason for emergency department attendance may be a new safety and efficacy factor in real-life patient scenarios.

Assessment of Adherence and Self-Efficacy in a Sample of Iraqi Patients Receiving Warfarin or Direct Oral Anticoagulants

Background: While warfarin and direct oral anticoagulants (DOACs) are used to manage thromboembolic events, they possess several features that impact adherence. Objective: To assess medication adherence and self-efficacy in patients receiving warfarin or DOAC treatment. Methods: A cross-sectional study was performed at Ibn Al-Bitar Hospital in Baghdad from December 2022 to May 2023 on patients receiving either warfarin or DOACs. The Arabic version of the Adherence to Refills and Medications Scale (ARMS) questionnaire and the Self-Efficacy for Managing Chronic Disease 6-Item Scale (SES6C) questionnaire were used to assess adherence and self-efficacy. Results: 181 patients were enrolled in the study, of whom 56.9% received warfarin and 43.1% received DOACs. The mean ARMS score was 13.71, and 81.77% of the patients were adherent to anticoagulant therapy. There was a significant difference in adherence between the warfarin and DOAC groups. The mean SES6C score for the participants was 50.01. Patients in the DOAC group had significantly higher self-efficacy compared to those in the warfarin group. The adherence score correlated significantly with patients’ gender, education level, hospitalization and duration of anticoagulant use, while the SES6C score did not correlate with any of the independent variables. There was a significant negative correlation between self-efficacy scores and medication adherence scores. Conclusions: Patients receiving DOACs showed a higher self-efficacy to manage chronic diseases and lower medication adherence as compared to warfarin. Higher self-efficacy was associated with higher adherence to treatment.

Comparison of Direct Oral Anticoagulants vs Vitamin K Antagonists After Transcatheter Mitral Valve Replacement

BackgroundThere is currently no established recommendation for antithrombotic treatment following transcatheter mitral valve replacement (TMVR). However, based on the analogy with surgical mitral bioprosthesis, vitamin K antagonists (VKAs) are predominantly used. ObjectivesThe purpose of this study was to compare bleeding and thrombotic events associated with direct oral anticoagulants (DOACs) or VKAs in a prospective cohort of TMVR patients. MethodsWe enrolled consecutive patients who underwent transseptal TMVR using a SAPIEN family prosthesis at our center between 2011 and 2023. The primary outcome was the occurrence of bleeding. VKAs were administered to patients until October 2019, after which DOACs were prescribed. The median follow-up was 4.7 months (Q1-Q3: 2.6-6.7 months). ResultsA total of 156 patients were included. The mean age was 65 ± 18.5 years, and 103 patients (66%) were women. The median EuroSCORE II was 7.48% (Q1-Q3: 3.80%-12.97%). Of the participants, 20.5% received DOACs and 79.5% were treated with VKAs. The primary outcome was observed in 50 (40%) patients in the VKA group and 3 (9%) patients in the DOAC group (adjusted HR: 0.21; 95% CI: 0.06-0.74; P = 0.02). Treatment with DOAC was associated with a shorter length of hospital stay. No significant differences were found in terms of thrombotic events, major vascular complications, stroke, or death. ConclusionsThe use of DOACs after TMVR, compared with VKAs, appears to reduce the risk of bleeding complications and decrease the length of hospital stay for patients, without a significant increase in the risk of thrombotic events.

Comparison of direct oral anticoagulants and warfarin in chronic limb-threatening ischemia

ObjectiveThe role of direct oral anticoagulants (DOACs) in chronic limb-threatening ischemia after revascularization is unknown. Current evidence-based guidelines do not provide clear guidance on the role of anticoagulation or the selection of anticoagulant. Current practice is highly varied and based on provider and patient preference. The purpose of this study was to measure the impact of different anticoagulants on the incidence of major adverse limb events (MALEs) after revascularization for chronic limb-threatening ischemia, major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for major bleeding events. MethodsThis was a single-center, observational, retrospective cohort study. Subjects were eligible if they were 18 years or older; underwent endovascular or open revascularization for chronic limb-threatening ischemia, rest pain, or tissue loss; and were subsequently prescribed apixaban, rivaroxaban, or warfarin. The primary end point was the incidence of MALEs, including above-ankle amputation or major index-limb reintervention, within 1 year of index event. Secondary end points included the rate of all-cause mortality, MACEs, and incidence of International Society on Thrombosis and Haemostasis (ISTH) major bleeding. ResultsFrom January 1, 2017, to September 20, 2022, 141 patients met the inclusion and exclusion criteria and were reviewed. The median age was 67 years, with 92 patients prescribed apixaban or rivaroxaban and 49 patients prescribed warfarin. Of these, 42 patients were prescribed triple antithrombotic therapy, 88 dual antithrombotic therapy, and 13 anticoagulant monotherapy. The primary outcome of 1-year MALEs occurred in 36.7% of the warfarin group and 33.7% of the DOAC group (relative risk [RR], 1.09; 95% CI, 0.53-2.25; P = .72). Secondary outcomes of 1-year MACEs (10.2% vs 4.3%; RR, 2.35; 95% CI, 0.60-9.18; P = .18) and 1-year all-cause mortality (26.5% vs 16.3%; RR, 1.63; 95% CI, 0.70-3.78; P = .15) did not differ between the groups. The secondary safety outcome of 1-year ISTH major bleeding occurred in 16.3% of the warfarin group and 4.3% of the DOAC group (RR, 3.76; 95% CI, 1.07-13.19; P = .015). ConclusionsIn patients with chronic limb-threatening ischemia who were revascularized and prescribed anticoagulation with apixaban, rivaroxaban, or warfarin on discharge, no difference in MALEs, MACEs, or all-cause mortality was found. However, 1-year admissions for ISTH major bleeding were significantly higher among patients prescribed warfarin. A randomized trial may confirm these findings.

Efficacy and Safety of Direct Oral Anticoagulants in Pediatric Venous Thromboembolism: A Systematic Review and Meta-Analysis.

To assess the efficacy and safety of direct oral anticoagulants (DOACs) in comparison to standard-of-care (SOC) anticoagulants in the management and prophylaxis of thromboembolic events in pediatric populations. A comprehensive search of electronic databases was conducted to identify relevant studies published between January 1, 2015, and December 18, 2022. A meta-analysis was undertaken to evaluate the effect of DOACs on clinically significant endpoints, employing trial-level data with harmonized endpoint definitions. The primary outcome was venous thromboembolism (VTE). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The study was registered with INPLASY (2022120065). Three studies encompassing 934 subjects were included. The incidence of VTE was reduced in patients administered DOACs compared to those on SOC anticoagulants (OR 0.41 [95% CI 0.19-0.93], I²=0%, P = 0.03). No significant differences were observed between the DOAC and SOC groups in all-cause mortality (OR 0.50 [95% CI 0.07-3.59], I²=0%, P = 0.35) or serious adverse events (OR 0.75 [95% CI 0.50-1.12], I²=0%, P = 0.16). The risk of major bleeding (OR 0.50 [95% CI 0.13-1.87], I²=44%, P = 0.30) and clinically relevant non-major bleeding (OR 1.23 [95% CI 0.50-3.00], I²=0%, P = 0.65) exhibited no significant differences between the groups. DOACs are associated with a reduced risk of VTE in pediatric patients without increasing the risk of bleeding, all-cause mortality, or serious adverse events when compared to SOC anticoagulants. DOACs may be an alternative for the treatment and prevention of thromboembolic events in the pediatrics.

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients With Recent Direct Oral Anticoagulant Use: A Systematic Review and Meta-Analysis.

Intravenous thrombolysis (IVT) is an effective stroke therapy that remains underused. Currently, the use of IVT in patients with recent direct oral anticoagulant (DOAC) intake is not recommended. In this study we aim to investigate the safety and efficacy of IVT in patients with acute ischemic stroke and recent DOAC use. A systematic review and meta-analysis of proportions evaluating IVT with recent DOAC use was conducted. Outcomes included symptomatic intracranial hemorrhage, any intracranial hemorrhage, serious systemic bleeding, and 90-day functional independence (modified Rankin scale score 0-2). Additionally, rates were compared between patients receiving IVT using DOAC and non-DOAC by a random effect meta-analysis to calculate pooled odds ratios (OR) for each outcome. Finally, sensitivity analysis for idarucizumab, National Institutes of Health Stroke Scale, and timing of DOAC administration was completed. Fourteen studies with 247 079 patients were included (3610 in DOAC and 243 469 in non-DOAC). The rates of IVT complications in the DOAC group were 3% (95% CI, 3-4) symptomatic intracranial hemorrhage, 12% (95% CI, 7-19) any ICH, and 0.7% (95%CI, 0-1) serious systemic bleeding, and 90-day functional independence was achieved in 57% (95% CI, 43-70). The rates of symptomatic intracranial hemorrhage (3.4 versus 3.5%; OR, 0.95 [95% CI, 0.67-1.36]), any intracranial hemorrhage (17.7 versus 17.3%; OR, 1.23 [95% CI, 0.61-2.48]), serious systemic bleeding (0.7 versus 0.6%; OR, 1.27 [95% CI, 0.79-2.02]), and 90-day modified Rankin scale score 0-2 (46.4 versus 56.8%; OR, 1.21 [95% CI, 0.400-3.67]) did not differ between DOAC and non-DOAC groups. There was no difference in symptomatic intracranial hemorrhage rate based on idarucizumab administration. Patients with acute ischemic stroke treated with IVT in recent DOAC versus non-DOAC use have similar rates of hemorrhagic complications and functional independence. Further prospective randomized trials are warranted.

Effects of sufficient anticoagulation on ischemic stroke outcomes in patients with nonvalvular atrial fibrillation

Background: Optimal anticoagulation therapy reduces the risk of ischemic stroke in patients with nonvalvular atrial fibrillation (AF). Therefore, we aimed to evaluate the effects of prior anticoagulation therapy with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) on ischemic stroke outcomes in patients with nonvalvular AF.Methods: We enrolled 487 patients with ischemic stroke and nonvalvular AF between January 2013 and August 2020. The infarct volume was semi-automatically evaluated using diffusion-weighted magnetic resonance imaging. Patients were categorized into no anticoagulation, undertreated anticoagulation, and sufficient anticoagulation (with VKA or DOAC) groups based on their pre-admission anticoagulant use, and the clinical characteristics were compared between the groups.Results: Among the included patients, 374 (76.8%), 50 (10.3%), 10 (2.1%), and 53 (10.9%) patients received no anticoagulants, were undertreated with a VKA, were sufficiently treated with a VKA, and received DOACs, respectively, before stroke. Multivariate analysis revealed that optimal anticoagulation was independently associated with a low risk of severe stroke (odds ratio, 0.553; 95% confidence interval, 0.308–0.992; P=0.047). Additionally, the DOAC group had a significantly smaller mean infarct volume than the other groups (45.8±73.2, 45.0±69.1, 30.9±24.7, and 12.6±24.9 mL in the no anticoagulation, insufficient VKA, sufficient VKA, and DOAC groups, respectively; P=0.011).Conclusion: Sufficient pre-stroke anticoagulation is associated with mild stroke severity and good outcomes at 3 months post-stroke. Additionally, pre-stroke DOAC treatment is associated with smaller infarct volume in patients with ischemic stroke and nonvalvular AF.

Urine-based point-of-care testing for factor-Xa-inhibitors in acute ischemic stroke patients: a feasibility study.

Direct oral anticoagulants (DOACs) have become widely used in clinical practice for preventing thromboembolic events. Point-of-care testing methods, particularly those based on urine samples, offer a promising approach for rapid and accurate assessment of DOAC presence. This pilot study aims to evaluate the utility of a urine-based DOAC dipstick test as a point-of-care tool for identifying DOAB presence in acute ischemic stroke (AIS) or transient ischemic attack (TIA) patients. This prospective pilot study included patients with AIS/TIA eligible for DOAC-measurement. After exclusion of 3 patients, 23 patients with DOAC-intake (DOAC group; factor-Xa-inhibitors; n = 23) and 21 patients without DOAC-intake (control-group) remained for analyses. The urine-based DOAC dipstick test and parallel blood-based specific DOAC-level assessment were performed in all patients. Time-intervals of sampling urine/blood sampling and result of DOAC-test were recorded to analyze a potential time benefit based on dipstick evaluation. The urine-based DOAC dipstick test demonstrated high sensitivity (100%) and specificity (100%), correctly identifying all patients with anticoagulatory activity due to DOAC intake (i.e., anti-Xalevel ≥30 ng/mL). Moreover, the visual readout of the test provided semiquantitative information on drug-specific anti-Xa levels, showing a sensitivity of 83% and specificity of 93% to detect anti-Xa levels ≥120 ng/mL. The dipstick test exhibited a median time-benefit of 2:25 h compared to standard blood-based DOAC-level testing. The results of this pilot study underline the efficacy of urine-based point-of-care testing as a rapid and reliable method for assessing DOAC presence in patients with acute ischemic stroke. The value of this tool for clinical decision-making in stroke management needs to be established in future trials.Clinical Trial Registration: Clinicaltrails.org identifier [NCT06037200].

Comparison of the Efficacy and Safety of Left Atrial Appendage Closure and Direct Oral Anticoagulants for Atrial Fibrillation: A Meta-Analysis of Randomized Control Trials and Observational Studies.

The aim of this study was to compare the efficacy and safety of left atrial appendage closure (LAAC) and direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). This meta-analysis was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. Two investigators performed an online database search on PubMed, Web of Science, and Scopus databases from inception to October 31, 2023, without any language or time restrictions. Outcomes assessed in this meta-analysis included all-cause mortality, cardiovascular mortality, stroke, and major bleeding events. Eight studies were included in this meta-analysis, enrolling 7,629 participants with AF (4,287 in the DOAC group and 3,342 in the LAAC group). The pooled analysis showed that the risk of all-cause mortality was significantly higher in patients in the DOAC group compared to LAAC (relative risk (RR): 1.87, 95% confidence interval (CI): 1.50 to 2.34). The risk of cardiovascular mortality was 1.60 times higher in patients receiving DOACs compared to those receiving LAAC (RR: 1.60, 95% CI: 1.12 to 2.28). The risk of stroke was not significantly different between the two groups (RR: 1.15, 95% CI: 0.95 to 1.41). In conclusion, LAAC for AF patients proves to be safe and effective for stroke prevention, exhibiting a superior profile in terms of all-cause mortality, cardiovascular events, and major bleeding compared to oral anticoagulation (OAC). These findings prompt consideration of LAAC as a preferred treatment for cardiovascular event prevention in high-bleeding-risk patients.