Effectiveness Of Direct Oral Anticoagulants Research Articles

Trends of anticoagulant use and outcomes of patients with non-valvular atrial fibrillation: Findings from the RAFFINE registry

BackgroundThe management of non-valvular atrial fibrillation (AF) has evolved with the development of direct oral anticoagulants (DOACs). However, data regarding the effectiveness and safety of DOACs outside clinical trial settings are limited, and off-label dosing of DOACs has not been thoroughly investigated. MethodsWe examined the clinical outcomes of patients with non-valvular AF in the RAFFINE registry, a prospective registry of Japanese patients with AF who were followed-up for more than 3 years. ResultsAmong 3706 patients with non-valvular AF, 42.5% received warfarin and 44.7% received DOACs at baseline. The administration of DOACs increased annually. The mean CHADS2 and HAS-BLED scores were significantly higher in the warfarin group. The unadjusted all-cause mortality, cardiovascular mortality, and incidence of major bleeding events were higher in the warfarin group. The incidence of ischemic stroke/systemic embolism was not different between groups. After adjustment for baseline characteristics, the incidence of these events was not different between groups. Off-label dosing was performed for 32% of patients in the DOAC group, but this did not affect clinical outcomes. ConclusionsThe all-cause mortality, cardiovascular mortality, and incidence of major bleeding events were higher in the warfarin group than in the DOAC group. After adjustment, warfarin use was not associated with an increase in these events. Off-label dosing of DOACs is not rare and is not associated with reduced effectiveness. The impact of off-label dosing of each DOAC on clinical events should be assessed using a larger population.

Effectiveness and Safety of Oral Anticoagulants in the Treatment of Acute Venous Thromboembolism: A Nationwide Comparative Cohort Study in France.

Introduction Data from clinical trials indicate that direct oral anticoagulants (DOACs) are noninferior and safer than conventional therapy (low-molecular-weight heparin followed by a vitamin K antagonist [VKA]) for treating venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism (PE). This study compared the effectiveness and safety of DOACs and conventional therapy in a real-world setting. Methods This observational study used French national claims data of adult, treatment-naïve patients diagnosed with VTE (majority PE) who were hospitalized and treated for VTE with a DOAC (apixaban or rivaroxaban) or VKAs during 2013 to 2018. Patients with active cancer were excluded. After propensity score matching for each DOAC-VKA comparison, risks of bleeding, recurrent VTE, and all-cause mortality were compared at 6 months. Cox proportional hazards regression was used to estimate adjusted hazard ratios of the endpoints. Results A total of 58,137 patients were included (10,775 VKAs, 10,440 apixaban, 36,922 rivaroxaban). Propensity score-matched cohort sizes were 7,503 for apixaban and 9,179 for rivaroxaban. The hazard ratio (95% confidence interval) was significantly lower for apixaban than VKAs for bleeding requiring hospitalization (0.43 [0.32–0.59]), all-cause death (0.61 [0.51–0.74]), and first recurrent VTE (0.67 [0.52–0.85]). The hazard ratio was also significantly lower for rivaroxaban than VKAs for all-cause death (0.63 [0.53–0.74]) but not for bleeding requiring hospitalization (0.86 [0.69–1.07]) or first recurrent VTE (0.91 [0.74–1.13]). Conclusion Apixaban was associated with superior safety and effectiveness than VKAs. All-cause mortality was lower in both DOACs than VKAs. Our results support recommendations to use DOACs over VKAs for the treatment of VTE.

Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery: systematic review and network meta-analysis of randomised trials

ObjectiveTo systematically compare the effect of direct oral anticoagulants and low molecular weight heparin for thromboprophylaxis on the benefits and harms to patients undergoing non-cardiac surgery.DesignSystematic review and network meta-analysis...

Effect of Direct Oral Anticoagulants on Treatment of Geriatric Hip Fracture Patients: An Analysis of 15,099 Patients of the AltersTraumaRegister DGU®.

Background and Objectives: The increased use of direct oral anticoagulants (DOACs) results in an increased prevalence of DOAC treatment in hip fractures patients. However, the impact of DOAC treatment on perioperative management of hip fracture patients is limited. In this study, we describe the prevalence of DOAC treatment in a population of hip fracture patients and compare these patients with patients taking vitamin K antagonists (VKA) and patients not taking anticoagulants. Materials and Methods: This study is a retrospective analysis from the Registry for Geriatric Trauma (ATR-DGU). The data were collected prospectively from patients with proximal femur fractures treated between January 2016 and December 2018. Among other factors, anticoagulation was surveyed. The primary outcome parameter was time-to-surgery. Further parameters were: type of anesthesia, surgical complications, soft tissue complications, length of stay and mortality. Results: In total, 11% (n = 1595) of patients took DOACs at the time of fracture, whereas 9.2% (n = 1325) were on VKA therapy. During the study period, there was a shift from VKA to DOACs. The time-to-surgery of patients on DOACs and of patients on VKA was longer compared to patients who did not take any anticoagulation. No significant differences with regard to complications, type of anesthesia and mortality were found between patients on DOACs compared to VKA treatment. Conclusion: An increased time-to-surgery in patients taking DOACs and taking VKA compared to non-anticoagulated patients was found. This underlines the need for standardized multi-disciplinary orthopedic, hematologic and ortho-geriatric algorithms for the management of hip fracture patients under DOAC treatment. In addition, no significant differences regarding complications and mortality were found between DOAC and VKA users. This demonstrates that even in the absence of widely available antidotes, the safe management of geriatric patients under DOACs with proximal femur fractures is possible.

Decrease in incidence of oral anticoagulant-related intracerebral hemorrhage over the past decade in the Netherlands.

BackgroundData on oral anticoagulant-related (OAC) intracerebral hemorrhage (ICH) incidence are scarce. Most studies on incidence time trends were performed before the introduction of Direct Oral Anticoagulants (DOACs). Between 2008 and 2018, the number of OAC-users in the Netherlands increased by 63%, with the number of DOAC-users almost equaling that of Vitamin K Antagonists (VKA)-users. We aimed to determine the recent total and OAC-related ICH incidence and assess changes over the last decade, including the effect of DOAC introduction.MethodsAll adult non-traumatic ICH patients presenting in any of three hospitals in the enclosed region of South-Limburg, the Netherlands, were retrospectively included, during two 3-year time periods: 2007–2009 and 2017–2019. OAC-related ICH was defined as ICH in patients using VKAs or DOACs. We calculated the incidence rate ratio (IRR) between the two study periods.ResultsIn the 2007–2009 period, we registered 652 ICHs of whom 168 (25.8%) were OAC-related (all VKA). In the 2017–2019 period, we registered 522 ICHs, 121 (23.2%) were OAC-related (70 VKA and 51 DOAC). In 2007–2009, the annual incidence of total ICH and OAC-related ICH was 40.9 and 10.5 per 100,000 person-years, respectively, which decreased to 32.4 and 7.5 per 100,000 person-years in 2017–2019. The IRR for total ICH and OAC-related ICH was 0.67 (95%-CI: 0.60–0.75) and 0.58 (0.46–0.73), respectively.ConclusionBoth total ICH and OAC-related ICH incidence decreased over the past decade in South-Limburg, the Netherlands, despite the aging population and increasing number of OAC-users. The introduction of DOACs, and possibly an improved cardiovascular risk management and change in OAC prescription pattern, could explain these findings.

D-dimer levels in patients with nonvalvular atrial fibrillation and acute heart failure treated with edoxaban

BackgroundD-dimer levels can predict ischemic stroke in patients with acute heart failure (AHF). However, the effects of direct oral anticoagulants on D-dimer levels have not been investigated during admission for AHF in patients with atrial fibrillation (AF). This study examined D-dimer levels immediately after admission and following edoxaban initiation as a sub-analysis of a multi-center study that investigated the pharmacokinetics and pharmacodynamics of edoxaban in patients with nonvalvular AF (NVAF) and AHF. MethodsHospitalized patients with NVAF and AHF received edoxaban according to the label. The primary measure was the change in D-dimer levels on 7 consecutive days after admission for AHF. We also investigated differences according to prior edoxaban use (de novo at the time of admission or continuation). ResultsIn 10/13 (76.9%) de novo patients, D-dimer levels exceeded the reference value (1.0 µg/mL) at admission (mean, 2.12 µg/mL) and subsequently decreased in 9 patients (at final blood sampling: mean, 1.12 µg/mL); 1 patient did not fall below the reference value due to stasis dermatitis. In the continuation group, most patients had D-dimer levels below the reference value from Day 1 (mean, 0.93 µg/mL), and levels remained stable or decreased (at final blood sampling: mean, 0.49 µg/mL). No events of stroke were observed. ConclusionsD-dimer levels may be elevated in patients with NVAF and AHF, particularly in those without prior anticoagulant treatment. Edoxaban may be effective for lowering and keeping D-dimer levels, a biomarker for predicting ischemic stroke, below the reference value in patients with NVAF and AHF.

Safety and Efficacy of DOACs in Patients with Advanced and End-Stage Renal Disease.

The prevalence of chronic kidney disease (CKD) is increasing due to the aging of the population and multiplication of risk factors, such as hypertension, arteriosclerosis and obesity. Impaired renal function increases both the risk of bleeding and thrombosis. There are two groups of orally administered drugs to prevent thromboembolic events in patients with CKD who require anticoagulation: vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). Although VKAs remain the first-line treatment in patients with advanced CKD, treatment with VKAs is challenging due to difficulties in maintaining the appropriate anticoagulation level, tendency to accelerate vascular calcification and faster progression of CKD in patients treated with VKAs. On the other hand, the pleiotropic effect of DOACs, including vascular protection and anti-inflammatory properties along with comparable efficacy and safety of treatment with DOACs, compared to VKAs observed in preliminary reports encourages the use of DOACs in patients with CKD. This review summarizes the available data on the efficacy and safety of DOACs in patients with CKD and provides recommendations regarding the choice of the optimal drug and dosage depending on the CKD stage.

Effectiveness and Safety of DOACs in Atrial Fibrillation Patients Undergoing Catheter Ablation: Results from the China Atrial Fibrillation (China-AF) Registry.

Direct oral anticoagulants (DOACs) have increasingly become an alternative to warfarin in atrial fibrillation (AF) patients. Nonetheless, data on the effectiveness and safety of DOACs in periprocedural of catheter ablation (CA) in real-world practice was relatively rare. 3385 AF patients underwent initial CA and never used oral anticoagulant before enrollment between April 2013 and December 2018 were involved from China Atrial Fibrillation (China-AF) Registry. Warfarin, rivaroxaban and dabigatran were used in 1896 (56.0%), 718 (21.2%), and 771 (22.8%) patients, respectively. Propensity score matching was used to balance covariates across study groups. No significant differences were observed in rivaroxaban-warfarin, dabigatran-warfarin and dabigatran-rivaroxaban cohort for thromboembolic (TE) and major bleeding (MB) incidence. Similar results were also revealed in low-dose rivaroxaban (RLD)-warfarin, low-dose dabigatran (DLD)-warfarin and DLD-RLD cohort. However, the risk of non-MB was higher not only on standard-dose of rivaroxaban but also on RLD when compared with warfarin and with DLD, respectively. In this study, the incidence of TE and MB were both comparable in standard- or low-dose DOACs versus warfarin and between the two DOACs, whereas the risk of non-MB was higher in rivaroxaban than in warfarin and in RLD than in DLD.

Effectiveness and Safety of Direct Oral Anticoagulants in Thai Patients with Atrial Fibrillation: A Real-World Retrospective Cohort Study.

BackgroundDirect oral anticoagulants (DOACs) are commonly used to prevent stroke and systemic embolism in patients with atrial fibrillation (AF). However, studies into their effectiveness and safety in the Thai population have so far been limited.ObjectivesTo study the effectiveness and safety of warfarin and DOACs among Thai AF patientsMethodsA retrospective cohort study was conducted on AF patients at Ramathibodi Hospital from 2013 to 2018. All patients were followed for at least 1 year. Relevant clinical information was collected and compared between AF patient groups receiving warfarin, dabigatran, rivaroxaban, and apixaban. The primary outcome was a composite of major bleeding, ischemic stroke, and systemic thromboembolism. The secondary outcomes were all-cause mortality and disease-specific mortality caused by major bleeding, ischemic stroke, and systemic thromboembolism.ResultsA total of 1680 AF patients were enrolled in the study (warfarin 1193, apixaban 140, dabigatran 193, rivaroxaban 114). The estimated incidence of composite outcome was 16% [95% CI, 14−18%] and 12.4% [95% CI, 9.4−15.3%] in the warfarin and DOAC group, respectively, given a number needed to treat of 28 [95% CI, 3−52]. Compared with warfarin, DOACs were associated with both lower rate of all-cause mortality (4.9% [22/447] vs 8% [98/1193]) and lower disease-specific mortality (0.4% [2/447] and 1% [12/1193]).ConclusionsThis study suggests DOACs were associated with a lower risk of major bleeding, ischemic stroke, and systemic thromboembolism compared to warfarin in Thai patients with AF. Patients receiving DOAC also had a lower rate of all-cause mortality and disease-specific mortality.

Incidence of venous thromboembolism in advanced lung cancer and efficacy and safety of direct oral anticoagulants: a multicenter, prospective, observational study (Rising-VTE/NEJ037 study).

Background:Venous thromboembolism (VTE) is a well-known type of cancer-associated thrombosis and a common complication of malignancy. However, the incidence of VTE associated with lung cancer and the effectiveness of direct oral anticoagulants remain unclear. This study aimed to identify the incidence of VTE associated with lung cancer at the time of diagnosis or during treatment, the efficacy and safety of edoxaban, and associated risk factors.Methods:The Rising-VTE/NEJ037 study was a multicenter prospective observational study. Altogether, 1021 patients with lung cancer who were unsuitable for radical resection or radiation were enrolled and followed up for 2 years. Patients with VTE at the time of lung cancer diagnosis started treatment with edoxaban. The primary endpoint of this trial was the rate of newly diagnosed VTE after enrollment or recurrence rate 6 months after treatment initiation.Results:Data were available for 1008 patients. The median age was 70 years (range: 30–94 years), and 70.8% were men. Sixty-two patients had VTE at the time of lung cancer diagnosis, and 38 (9.9%) developed VTE at follow-up. No cases of VTE recurrence were recorded 6 months after treatment initiation with edoxaban. Major and clinically relevant non-major bleeding events occurred in 4.9% of patients and increased to 22.7% in the edoxaban treatment group.Conclusions:VTE occurrence should be monitored during lung cancer treatment. Although treatment with edoxaban was highly effective in preventing VTE recurrence, its administration should be cautiously considered because of the high bleeding rate.Trial registration:jRCTs061180025.

Efficacy and safety of direct oral anticoagulants versus warfarin in elderly patients with cancer-associated venous thromboembolism

Background Little is known about the effects of direct oral anticoagulants (DOACs) in cancer[1]related venous thromboembolism patients. Methods Data of patients with cancer-related venous thromboembolism (VTE) were retrieved from King Abdulaziz Medical City Database during 2016–2020. We excluded patients who were not using oral anticoagulants, used anticoagulants for <30 days, used 2 agents concomitantly or switched anticoagulants,were aged <65. The primary outcomes were recurrent VTE,major bleeding, and death from any cause. Results We identified 717 patients who received a diagnosis of cancer-related VTE. After the exclusion criteria were applied, 445 patients remained, 298 were used warfarin, and 147 were received NOACs. Both groups were followed up for 12±2 months. The mean age of the patients was 71 ± 8 in the DOACs group and 76 ±6 in the warfarin group (p > 0.05); 48.24% of patients in the DOAC group and 46.98% of patients in the warfaringroup were men (p > 0.05). The mean HAS-BLED score was 3.7 ± 3.8 in the NOAC group and 3.8 ± 3.9 in the warfaringroup (p > 0.05). Furthermore, among patients with cancer-related VTE, DOAC was associated with no difference in major bleeding or recurrence events (CRR = 0.91, 95% CI = 0.78–1.05; CRR = 0.63, 95% CI = 0.52–0.77, respectively), and significantly reduced death from any cause (aHR = 0.65, 95% CI = 0.52–0.80) compared with warfarin. Conclusions In elderly patients with cancer-related VTE, DOAC was associated with reduced death from any cause compared with warfarin, whereas no difference in major bleeding or recurrent VTE were observed between these treatment modalities.

Direct oral anticoagulants versus vitamin K antagonists in the treatment of left ventricular thrombosis: a systematic review and meta-analysis.

Evidence about the use of direct oral anticoagulants (DOACs) in patients with left ventricular thrombosis (LVT) are emerging. The aim of our study was to provide a comprehensive synthesis of the available evidence concerning the clinical effects of DOACs versus vitamin K antagonists (VKAs) in LVT treatment. Systematic search of studies evaluating DOACs versus VKAs use in patients with LVT was performed on May 11th, 2021. Data were pooled by meta-analysis using a random-effects model. Odds ratios (OR) with relative 95% confidence intervals (CI) were used as measures of effect estimates. The primary efficacy and safety endpoint were ischemic stroke and any bleeding, respectively. Secondary endpoints were LVT resolution, systemic embolism, major bleeding, hemorrhagic stroke, and all cause death. Twenty studies were included in the meta-analysis: 1,391 patients were treated with DOACs and 1,534 with VKAs. A significant reduction in the risk of ischemic stroke (OR 0.67, 95% CI, 0.45-0.98, P=0.048, number needed to treat to benefit [NNTB] 22 [95% CI 15-43]) and any bleeding (OR 0.64, 95% CI 0.46-0.89, P=0.009, NNTB 26 [95% CI 16-80]) was observed with DOACs compared to VKAs. No statistically significant difference was observed among the two treatment arms for the secondary endpoints. Compared to VKAs, DOACs are associated with a reduced risk of ischemic stroke and bleeding. In light of these findings, and the practical advantages of DOACs, additional large scale randomized controlled trials are needed to confirm the benefits of DOACs in patients with LVT.

Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients

Background/Aim. Direct oral anticoagulants (DOACs) administration significantly interferes with coagulation as-says. The aim of the study was to evaluate the effect of DOACs and DOAC-Remove? on coagulation assays during thrombophilia testing. Methods. The study was carried out from January 2019 to the end of June 2020. It included 30 DOAC-treated patients, 14 females and 16 males aged 23 to 63 (median age 47.6 years), tested for thrombophilia due to venous thromboembolism (VTE). Thrombophilia testing was performed using DOAC-Remove? tablets (activated charcoal). The results before and after DOAC-Remove? were compared. Results. Positive lupus anticoagulant (LA) results were observed in 20% apixaban, 100% dabigatran, and 70% rivaroxaban-treated patients, while in samples after DOAC-Remove?, the LA positivity was observed only in one from the apix-aban group. Before DOAC-Remove?, the activated protein C (APC) resistance (APC-R) was measurable in 40% dabigatran and 80% rivaroxaban-treated patients, while, after using DOAC-Remove?, the APC-R was measurable in all cases. Comparing the results obtained from the samples before and after DOAC-Remove?, a difference was noted in relation to all dilute Russell?s viper venom time (dRVVT) coagulation tests, except for the dRVVT ratio in the apixaban group. Clot-based methods for detecting the APC resistance were significantly affected by dabigatran and less by rivaroxaban. Conclusion. DOACs were practically inactivated after the addition of the DOAC-Remove?, which made it possible to perform analyses for the LA and APC-R testing freely and obtain relevant results.

Safety and Effectiveness of Direct Oral Anticoagulants vs. Warfarin in Patients With Atrial Fibrillation and Endoscopy-Diagnosed Peptic Ulcer.

Background: Patients with active peptic ulcer (PU) were excluded from direct oral anticoagulant (DOAC) trials for stroke prevention in patients with atrial fibrillation (AF). This study evaluated the safety and effectiveness of DOACs in AF patients with active, inactive and no peptic ulcer (PU).Methods: This study accessed electronic medical records from January 1, 2009 to May 31, 2019 at a multi-center healthcare provider in Taiwan and involved 2,955 AF patients who had undergone esophagogastroduodenoscopy ≤ 1 year before anticoagulation. Subjects were classified into 3 groups: active (n = 237), inactive (n = 828) and no-PU (n = 1,890) groups. We compared the risks of major bleeding, gastrointestinal bleeding, and ischemic stroke/systemic embolism (IS/SE) between DOACs and warfarin among the 3 groups.Results: In the active PU group, there were no significant differences in the risks of major bleeding [hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.08–4.98, p = 0.676], gastrointestinal bleeding (HR = 0.65, 95% CI 0.08–4.98, p = 0.676) and IS/SE (HR = 2.58; 95% CI 0.53–12.70, p = 0.243) between DOAC and warfarin (as the reference). In the inactive PU group, there were no significant differences in the risks of major bleeding (HR = 0.36, 95% CI 0.09–1.39, p = 0.138), gastrointestinal bleeding (HR = 0.21, 95% CI 0.02–1.80, p = 0.153), and IS/SE (HR = 1.04, 95% CI 0.39–2.82, p = 0.934) between DOAC and warfarin (as the reference). In the no-PU group, DOACs were associated with lower risk of major bleeding (HR = 0.26, 95% CI 0.12–0.53, p < 0.001), gastrointestinal bleeding (HR = 0.25, 95% CI 0.01–0.59, p = 0.002), and similar risk of IS/SE (HR = 0.92, 95% CI 0.55–1.54, p = 0.757) compared to warfarin.Conclusions: DOACs were as effective as warfarin in preventing IS/SE irrespective of PU status and safer than warfarin in reducing major bleeding in the no-PU group. In patients with active or inactive PUs, DOAC and warfarin were not significantly different in their effects on major bleeding or gastrointestinal bleeding.

Examination of the Effectiveness of Direct Oral Anticoagulants in Comparison to Warfarin in an Obese Population.

Background: While commonly prescribed today, direct oral anticoagulants (DOACs) have historically been avoided in patients with class III obesity or a weight >120 kg due to limited literature regarding the efficacy and safety in this population. Objective: The overall objective was to examine the effectiveness of DOACs compared to warfarin in a population with obesity. Methods: Patients with a diagnosis of venous thromboembolism (VTE) or atrial fibrillation and a body mass index (BMI) ≥35 kg/m2 from August 1, 2015, to August 1, 2020, were included in this retrospective cohort study. Patients receiving a DOAC were matched in a 1:2 ratio to warfarin. The primary outcome was a composite of stroke or recurrent VTE. Secondary outcomes included the individual components of the primary outcome, hospitalization for bleed, and the primary outcome in patients with a BMI ≥40 kg/m2. Results: A total of 162 patients were included, with 54 and 108 in the DOAC and warfarin groups, respectively. Baseline BMI was similar between groups (45.7 kg/m2 for DOACs vs 43.8 kg/m2 for warfarin), with approximately 70% of patients having a BMI ≥40 kg/m2. The primary outcome occurred in 1 patient (1.9%) in the DOAC group and 2 patients (1.9%) in the warfarin group. The DOAC group had a higher, nonsignificant incidence of bleeding (5.6% vs 0.9%, P = 0.11). There was no difference between groups in incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), or stroke in patients with a BMI ≥40 kg/m2. Conclusion: DOACs may be as efficacious as warfarin in the prevention of stroke or recurrent VTE in patients with a BMI of ≥35 kg/m2. Prospective, randomized trials are warranted to further assess the efficacy and safety of DOACs in this population.

Direct oral anticoagulants are associated with potentially bleeding lesions in suspected mid-gastrointestinal bleeding

Background and aim Direct oral anticoagulants (DOACs) became a widespread alternative in anticoagulant therapy. Nevertheless, concerns are raised about their safety, with increased gastrointestinal bleeding rates being described. There are scarce studies regarding DOACs effect on small-bowel capsule endoscopy (SBCE) findings. We aimed to assess if the detection of lesions with high bleeding potential on SBCE was significantly different in patients treated with DOACs when compared to non-anticoagulated patients and to patients anticoagulated with other agents. Methods Cohort study including consecutive patients who underwent SBCE for suspected mid-gastrointestinal bleeding (MGIB) in 2019 and 2020. Results From 148 patients, 38 (25.7%) were anticoagulated, of which 26 (68.4%) with DOACs. P2 lesions were detected in 36.5% (n = 54) of the patients. These lesions were more frequently detected in patients under DOACs treatment when compared to non-anticoagulated patients (69.2% vs. 29.1%; p=.001), and also when compared to patients treated with other anticoagulants (69.2% vs. 33.3%; p=.037). No differences in P2 lesions detection were observed between patients treated with other anticoagulants and non-anticoagulated patients (33.3% vs. 29.1%; p=.747). In multivariate analysis, DOACs usage was significantly associated with higher detection rates of P2 lesions on SBCE, when adjusted for classical risk factors for MGIB (OR: 3.38; 95%CI = 1.23–9.26; p=.018). Conclusions Despite their undeniable cardiovascular benefits and easy applicability, DOACs should still be considered with caution. These drugs were significantly associated with higher risk of potentially bleeding lesions on SBCE when compared to other anticoagulants and represent an independent risk factor for MGIB when adjusted for other variables.

21 Direct oral anticoagulants vs. vitamin K antagonists in the treatment of left ventricular thrombosis: a systematic review and meta-analysis

Abstract Aims Evidence about the use of direct oral anticoagulants (DOACs) in patients with left ventricular thrombosis (LVT) are emerging. The aim of our study was to provide a comprehensive synthesis of the available evidence concerning the clinical effects of DOACs vs. vitamin K antagonists (VKAs) in LVT treatment. Methods Systematic search of studies evaluating DOACs vs. VKAs use in patients with LVT was performed on 11 May 2021. Data were pooled by meta-analysis using a random-effects model. Odds ratios (OR) with relative 95% confidence intervals (CI) were used as measures of effect estimates. The primary efficacy and safety endpoint were ischaemic stroke and any bleeding, respectively. Secondary endpoints were LVT resolution, systemic embolism, major bleeding, haemorrhagic stroke, and all cause death. Results Twenty studies were included in the meta-analysis: 1391 patients were treated with DOACs and 1534 with VKAs. A significant reduction in the risk of ischaemic stroke [OR 0.67, 95% CI 0.45–0.98, P = 0.048, number needed to treat to benefit (NNTB) 22 (95% CI 15–43)] and any bleeding [OR 0.64, 95% CI 0.46–0.89, P = 0.009, NNTB 26 (95% CI 16–80)] was observed with DOACs compared to VKAs. No statistically significant difference was observed among the two treatment arms for the secondary endpoints. Conclusion Compared to VKAs, DOACs are associated with a reduced risk of ischaemic stroke and bleeding. In light of these findings, and the practical advantages of DOACs, additional large scale randomized controlled trials are needed to confirm the benefits of DOACs in patients with LVT.

Association between anti F-Xa activity and plasma levels in patients with non valvular atrial fibrillation on apixaban

Apixaban, a Factor Xa inhibitor, has been shown to confer superior net clinical benefit compared to warfarin in the management of patients with non-valvular atrial fibrillation (NVAF). While warfarin effect can be easily monitored using INR measurements, assessment of anti-Factor Xa activity level is currently not readily available. Effects of direct oral anticoagulants have been shown to be related to their plasma levels.

Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation.

ObjectiveTo investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years.MethodsIndividual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all‐cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk.ResultsIn total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient‐years follow‐up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y = 0.65, 95%‐CI [0.52, 0.81]) and < 85 years (HR<85y = 0.79, 95%‐CI [0.66, 0.95]) in simple (pinteraction = 0.129), adjusted (pinteraction = 0.094) or weighted (pinteraction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient‐years for ICH‐weights 1.5 to 3.1).InterpretationThe favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2022;91:78–88

Equivalence of DOACS and LMWH for thromboprophylaxis after hip fracture surgery: Systematic review and meta-analysis

BackgroundPatients with hip fractures (HF) have an increased risk of venous thromboembolism (VTE). In elective orthopedic surgery direct oral anticoagulants (DOACs) have proven to be similarly or more effective compared to low molecular weight heparin (LMWH), but DOACs are not yet approved for thromboprophylaxis in trauma patients with HF. The aim of this study was to systematically review the literature comparing the effectiveness of DOACs and LMWH for thromboprophylaxis in trauma patients with surgically treated HF. Materials and MethodsWe searched PubMed, the Cochrane Library, Web of Science, and Embase. The primary outcome was the incidence of VTE (symptomatic and asymptomatic combined). Secondary outcomes were symptomatic VTE; a symptomatic VTE, symptomatic deep venous thrombosis (DVT); symptomatic pulmonary embolism (PE); major, clinically relevant non-major (CRNM), and minor bleeding. Meta-analysis was performed to compare the odds of VTE and secondary outcomes between DOACs and LMWH. ResultsThe search resulted in 738 titles. Five studies matched inclusion criteria. In total, 4748 hip fracture patients were analyzed (DOACs: 2276 patients, LMWH: 2472 patients). The pooled odds ratio for the risk of VTE for DOAC use was 0.52 (95% confidence interval 0.25–1.11, p = 0.09) compared to LMWH. No statistically significant differences between DOAC and LMWH were found for asymptomatic VTE, symptomatic DVT, PE, major or CRNM bleeding, and minor bleeding. ConclusionsMeta-analysis of the literature suggests that DOACs are associated with equivalent effectiveness and safety compared to LMWH.