Comparison of warfarin and direct oral anticoagulants in kidney transplant recipients: Safety and efficacy outcomes.

Outcomes of Direct Oral Anticoagulant- and Warfarin-Associated Hemorrhage: A Single Center Retrospective Cohort Study

the efficacy and safety of direct oral anticoagulants (DOACs) compared with that of warfarin in very old patients with non-valvular atrial fibrillation (NVAF) have been reported in terms of thromboembolisms and bleeding. However, the association of DOAC use and mortality in such patients remains unclear. this study aimed to investigate the incidence of mortality, as well as thromboembolisms and major bleeding, in very old patients with NVAF using DOACs as compared with warfarin. we conducted a single-centre historical cohort study of consecutive patients with NVAF aged ≥80years who used oral anticoagulants. We compared the 5-year outcomes (all-cause mortality, thromboembolism, major bleeding and intracranial haemorrhage) between the DOAC and Warfarin groups. of 1,676 patients with atrial fibrillation aged 80years and over, 1,208 with NVAF were included. Propensity score matching provided 461 patients in each group, and the risk of all-cause mortality, thromboembolisms, major bleeding and intracranial haemorrhages was significantly lower in the DOAC group than Warfarin group (hazard ratio [95% confidence interval] for DOAC use, 0.68 [0.54-0.87], 0.31 [0.19-0.53], 0.56 [0.36-0.88], 0.23 [0.10-0.56], log-rank P = 0.002, P < 0.001, P = 0.010, P < 0.001). The mortality rate within 1year after major bleeding was significantly lower in the DOAC group than Warfarin group (14% versus 38%, P = 0.03), however, that after a thromboembolism was similar between the two groups (33% versus 35%). patients with NVAF aged ≥80years and using DOACs had a lower mortality than those using warfarin.

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.

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.

Simple SummaryThis prospective phase II trial evaluated the safety and efficacy of direct oral anticoagulants (DOACs) versus subcutaneous dalteparin for cancer-associated venous thromboembolism (CA-VTE) in patients with high-risk cancer types and currently active advanced cancers. The clinically relevant bleeding (CRB) as the primary endpoint and major bleeding (MB) more occurred in the DOAC group than in the dalteparin group, and the hazard ratio for CRB and MB was approximately three and four times more in the DOAC group than in the dalteparin group. Cancer involvement at the GI mucosa was also a significant risk factor for CRB. The extra caution is necessary when using DOAC therapy for CA-VTE in patients with advanced upper gastrointestinal (GI) tract, hepatobiliary, or pancreatic cancer.Background: We evaluated the safety and efficacy of direct oral anticoagulants (DOACs) versus subcutaneous dalteparin for cancer-associated venous thromboembolism (CA-VTE) in patients with advanced upper gastrointestinal (GI) tract, hepatobiliary, or pancreatic cancer. Methods: This was a multicenter, randomized, open-label, phase II trial in five centers. Patients randomly received rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily)/apixaban (10 mg twice daily for the first 7 days, then 5 mg twice daily) or dalteparin (200 IU/kg once daily for the first month, then 150 IU/kg once daily). Randomization was stratified by the Eastern Cooperative Oncology Group Performance Status, primary cancer type, active chemotherapy, and participating centers. The primary endpoint was the rates of clinically relevant bleeding (CRB) in the full analysis set (FAS). Results: A total of 90 patients were randomly assigned to the DOAC (n = 44) and dalteparin groups (n = 46) in FAS. CRB and major bleeding (MB) rates were 34.1% and 13.0% (p = 0.018) and 18.2% and 4.3% (p = 0.047) for the DOAC and dalteparin groups, respectively. Time to CRB and MB was higher in the DOAC group than in the dalteparin group (hazard ratio [HR] 2.83; p = 0.031 and HR 4.32; p = 0.064). Cancer involvement at the GI mucosa was also a significant risk factor for CRB. Recurrent CA-VTE occurred in 2.3% and 2.2% of patients given DOAC and dalteparin, respectively (p = 1.000). Conclusion: DOAC therapy further increased the risk of bleeding compared with dalteparin in patients with active advanced upper GI tract, hepatobiliary, or pancreatic cancer, suggesting that extra caution should be taken when selecting anticoagulants for CA-VTE.

Impact of direct-acting oral anticoagulants and warfarin on postendoscopic GI bleeding and thromboembolic events in patients undergoing elective endoscopy

Background: Patients undergoing anticoagulation therapy often experience intracerebral hemorrhages (ICHs), and warfarin in particular is known to increase hematoma expansion in ICHs, which results in a poor outcome. Recent studies reported that, in comparison with warfarin, direct oral anticoagulants (DOACs) cause fewer ICHs with better functional outcome. However, since it is still unknown whether DOACs are associated with a smaller hematoma volume of ICHs, we aimed to compare the volume, hematoma expansion, and outcomes associated with ICHs treated with DOACs and warfarin. Methods: We performed a prospective multicenter cross-sectional study. The subjects included patients with acute ICHs who received either DOACs or warfarin. We evaluated the clinical characteristics, and measured initial and follow-up ICH volumes. The volume of ICHs and hematoma expansion were compared between the DOAC and warfarin groups. Mortality and modified Rankin score at discharge were evaluated as outcomes. Results: There were 18 patients in the DOAC group and 71 in the warfarin group. The baseline characteristics were similar between the 2 groups. Initial median hematoma volume of ICHs in the DOAC group was significantly lower than that in the warfarin group (6.2 vs. 24.2 mL, respectively; p = 0.04). In cases involving follow-up computed tomography scanning, the median hematoma volume of ICHs at follow-up was lower in the DOAC group than in the warfarin group (initial: DOACs 4.4 vs. warfarin 13.5 mL; follow-up: 5.0 vs. 18.4 mL, respectively; p = 0.05). Further, the hematoma in ICHs associated with DOACs did not expand. Although the mortality of ICHs associated with DOACs (11%) was lower than that associated with warfarin (24%), this difference was not statistically significant. The univariate analysis showed that the anticoagulant type (DOACs vs. warfarin) and sex (male vs. female) were associated with ICH volume. The multivariable linear regression showed that the use of DOACs (compared to warfarin; β: –0.23, p = 0.03) and female sex (compared to male; β: –0.25, p = 0.02) were associated with a small hematoma volume. Conclusions: Based on the results of the present study, in terms of the risks associated with ICHs, the use of DOACs appears to be safer than warfarin for anticoagulation therapy. Further studies are required to validate these findings.

<b>Background:</b> Long-term outcome data on direct oral anticoagulants (DOACs) for treating acute pulmonary embolism (PE) in obesity is limited. <b>Aim:</b> We evaluated the efficacy and safety of DOACs compared to warfarin in obesity associated PE. <b>Methods:</b> A multisite propensity-scores matched case-control study was performed. Adults with a BMI &gt;30kg/m² with acute PE requiring hospital admission and initiated on anticoagulation were eligible, and matched 2:1 to DOAC and warfarin groups. Outcomes were compared at six-months. <b>Results:</b> Out of 1682 hospital presentations with acute PE during the study period, 271 patients (median age 59 years [IQR 41-78]) met inclusion criteria and underwent matching to DOACs (N=154) and warfarin (N=77) groups. Recurrent VTE rate within six-months was 5.8% (n=9) in DOAC group compared to 6.6% (n=5) in warfarin group (OR 0.89; 95%CI 0.3-2.8, p=0.85). Overall rate of bleeding complications was similar between DOACs and warfarin groups (14.3% vs 16.9% respectively, OR 0.82; 95%CI 0.4–1.7, p=0.60). Thirty-day mortality was 1.3% (n=2) in DOAC group and 3.9% (n=3) in warfarin group (OR 0.32; 95%CI 0.1-2.0, p=0.22). Morbidly obese (BMI &gt;40 kg/m² or weight &gt;120kg) patients had similar recurrent VTE rates (5.8% in the DOAC group vs 6.8% in the warfarin group (OR 0.89; 95% CI 0.2-3.6, p=0.82)) and bleeding complications. In patients with intermediate or high-risk PE, the rate of recurrent VTE was 4.3% (n=5) in DOAC group compared to 6.6% (n=4) in warfarin group (OR 0.65; 95%CI 0.2-2.5, p=0.52). <b>Conclusion:</b> Anticoagulation with DOACs appears to be effective and safe in obese patients with acute PE compared to warfarin, including in intermediate or high-risk PE.

Comparison between DOACs and warfarin for left atrial thrombus in atrial fibrillation patients.

BackgroundNephrotic syndrome (NS) is associated with an increased risk of venous thromboembolism (VTE). Anticoagulants are widely used in the prevention of VTE in NS patients. The use of direct oral anticoagulants (DOACs) has not been studied intensively in NS patients. The aim of this study is to determine the efficacy and safety of DOACs compared to warfarin for prophylactic anticoagulation in patients with nephrotic syndrome.MethodsRetrospective analysis conducted in a tertiary hospital-based ambulatory anticoagulation clinic between 01/07/2016 and 29/11/2021. We aimed to evaluate the incidence of VTE, major bleeding, and non-major bleeding in both the DOACs and warfarin groups.ResultsFifty-seven patients were recruited, 31 patients were prescribed warfarin (54.4%), and 26 were on DOAC (45.6%). Two patients in the DOAC group developed VTE, while no subjects in the warfarin group developed VTE, however, the difference was not statistically significance (p = 0.2). Nine out of 31 patients in the warfarin group developed non-major bleeding compared to three patients in the DOAC group (p = 0.02). One patient developed major bleeding in each group DOAC group 1 (15.4%), warfarin 1 (12.9%) (p = 1.00). There was no statistically significant difference in major bleeding between DOAC and warfarin groups (p = 1.00).ConclusionIn patients with NS, preliminary evidence suggests that DOACs have comparable efficacy as compared to warfarin when used as prophylaxis. Additionally, DOACs result in lower incidences of non-major bleeding. However, further studies are indicated to confirm the superiority of DOACs over warfarin.

EFFICACY AND SAFETY OF DIRECT ORAL ANTICOAGULANTS (DOACS) IN MORBIDLY OBESE PATIENTS

Drug-related problems (DRPs) in a pharmacist-managed anticoagulation clinic (AC) have not been extensively studied. We aimed to characterize the DRPs in a pharmacist-managed AC, identify the factors associated with the solved status of DRPs, and analyze the secondary outcomes, including the safety and efficacy of AC service. The patients receiving services at a pharmacist-managed AC in a medical center for the first time from March 2019 to August 2020 were reviewed retrospectively. The DRPs were retrieved from a self-developed Intelligent AC Service System and classified according to the Pharmaceutical Care Network Europe Foundation v9.0 classification system. Logistic regression models were performed to identify the potential factors associated with the solved status of DRPs. A total of 78 direct oral anticoagulant (DOAC) and 34 warfarin users were included. The major types of DRPs identified at the initial service were adverse drug events (ADEs) (68.4%) and untreated symptoms or indications (14.8%) in the DOAC group, and ADEs (51.6%) and suboptimal effect of drug treatment (38.7%) in the warfarin group. The rates of totally solved DRPs were 56.8% and 51.6% in the DOAC and warfarin groups, respectively. According to the multivariable analysis, receiving AC services 3 times or more in 180 days (OR 3.11, 95% CI 1.30–7.44) was associated with the totally solved status of DRPs in the DOAC group, but no relevant factor was identified in the warfarin group. The secondary outcomes showed that DOAC users demonstrated fewer thromboembolism events, major bleeding, and bleeding-related hospitalizations after AC services, whereas the warfarin users increased percentage time in therapeutic range (TTR% 55.0% vs. 74.6%, P = 0.006) after AC services. These findings may be utilized to develop DOAC and warfarin AC services.

Relationship between the nutritional status and safety and efficacy outcomes in atrial fibrillation patients aged 80 years and over receiving oral anticoagulants

Background: Direct oral anticoagulants (DOACs) are commonly used for the treatment/prevention of thromboembolism. Data supporting the best practices for anticoagulation management, specifically with DOACs, at the time of solid organ transplant is limited. This study was designed to compare the perioperative bleeding risk of warfarin vs DOACs in kidney transplant recipients. Methods: This was a single center, retrospective, cohort study evaluating patients on either a DOAC or warfarin prior to kidney transplant. The primary outcome compared a composite of perioperative bleeding risk at 30days of major bleeding and clinically relevant non-major bleeding. Secondary outcomes evaluated the incidence of type of bleeds, thromboembolism, hospital length of stay, blood product receipt, and patient/graft survival. Results: 67 kidney transplant recipients were included (n = 39 warfarin and n = 28 DOAC). The primary outcome of the composite of incidence of bleeding was no different between groups (21.4% vs 28.2% in DOAC vs warfarin groups, P = 0.52). More warfarin patients met criteria for major bleeding (20.5% vs 14.3%, P = 0.13) but this was not statistically significant. Minor bleeds were similar between DOAC vs warfarin groups (7.7% vs 7.1%, P = 0.99). Hospital length of stay was longer for warfarin patients (median [IQR] days 8 [5-12.3] vs 5 [4-6], P < 0.0001). There was no difference in the other outcomes. Conclusions: This study found no difference in risk of bleeding between groups, however warfarin patients required higher volumes of blood products and had longer hospital length of stays. This study supports DOAC use in the perioperative setting for kidney transplant recipients.

Background: Limited clinical data exists regarding use of direct oral anticoagulants (DOACs) in extreme obesity, specifically those ≥140 kg or having a body mass index (BMI) ≥ 50 kg/m2. Objective: Evaluate the safety and efficacy of DOACs in extreme obesity. Patients/Methods: A retrospective chart review was performed at a single center of patients aged 18-89 years and weight ≥140 kg or BMI ≥50 kg/m2 receiving warfarin or DOAC therapy. Patients were followed for 1 year from prescribing/study inclusion. The primary outcome was the difference in rates of any bleed (composite of major, nonmajor clinically relevant, or minor bleeding events as defined by International Society of Thrombosis and Haemostasis (ISTH) criteria) between groups. Secondary outcomes included individual components of the composite primary outcome and effectiveness in preventing thrombotic events within 12 months. Post-hoc multivariate analysis evaluated potential predictors of bleeding events within overall patient population. Results: Two-hundred eighty-five patients were included, 80 and 205 in the DOAC and warfarin groups, respectively. Rates of any documented bleeding event were comparable in DOAC and warfarin groups (17.5% vs 17.1%, P > .05). No significant difference in rates of minor (P = .067), nonmajor clinically relevant (P = .825), and major (P = 1) bleeding events were observed. Two thrombotic events occurred in the warfarin group compared to none in the DOAC group. Increasing weight was associated with bleeding events in multivariate analysis. Conclusions: This data did not demonstrate a difference in safety or efficacy outcomes between DOACs and warfarin when utilized in patients with extreme obesity.