Use Of Direct Oral Anticoagulants In Patients 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.

Retrospective, multicenter analysis of the safety and effectiveness of direct oral anticoagulants for the treatment of venous thromboembolism in obesity.

Direct oral anticoagulants (DOACs) are the preferred treatment for venous thromboembolism (VTE). However, DOAC use in patients with a BMI greater than 40kg/m2 has not been well studied despite the growing prevalence of obesity, and current literature is often underpowered. This multicenter, retrospective, observational study evaluated patients 18 years and older who received DOACs for acute VTE treatment. Patients receiving DOACs for recurrent VTE or for failure of another agent were excluded. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding within 12 months (or one month after stopping anticoagulation therapy). A propensity score analysis was performed to balance patient characteristics and evaluate the primary endpoints by BMI group. Time-to-event outcomes were analyzed using weighted Kaplan-Meier curves. There were 165 patients with a BMI of at least 40kg/m2 and 320 patients with a BMI less than 40kg/m2. The majority received apixaban (373, 77%). Recurrent VTE occurred in 5 (3.0%) and 13 (4.1%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 0.66; 95% CI: 0.16-2.69). Major bleeding occurred in 5 (3.0%) and 15 (4.7%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 1.19; 95% CI: 0.36-3.92). There was no significant difference in VTE recurrence or major bleeding related to BMI among patients treated with DOACs. This study showed that DOACs may be a safe and effective VTE treatment option in patients with obesity.

Clinical Characteristics and Anticoagulation Use in Antiphospholipid Syndrome: A Single-Center Retrospective Analysis

Background: Warfarin remains the anticoagulant of choice for patients with antiphospholipid syndrome (APLS). However, conflicting data exists regarding the role of direct oral anticoagulants (DOACs) as reasonable alternatives to warfarin, which has a less desirable side effect profile. In clinical practice, some patients start taking DOACs or aspirin before an official APLS diagnosis is confirmed and these patients may choose to continue a DOAC after an informed discussion with their hematologist. To gain a better understanding of anticoagulant use in APLS at our center, we conducted a retrospective study to assess the clinical characteristics of patients diagnosed with APLS. Methods: All patients with an ICD-10 code indicating APLS from January of 2020 to April of 2023 were included. Patient characteristics, relevant laboratory testing (lupus anticoagulant, beta-2 glycoprotein IgG/IgM, and anti-cardiolipin IgG/IgM), and treatment history were extracted from the electronic medical record. Patients were deemed to have single positivity if any one of the following were present: detectable lupus anticoagulant, elevated (defined as >40 GPL) beta-2 glycoprotein (B2GP) IgG or IgM, or elevated cardiolipin IgG or IgM both on initial and confirmatory testing (performed approximately 12 weeks later). Similarly, double positivity was defined as the presence of two of these biomarkers and triple positive was defined as the presence of three of these biomarkers. Initial laboratory testing results are included in Table 1. Statistical analysis was conducted using the SAS software (SAS Enterprise Guide 7.1) and the R Core Team (R 4.2.2). Continuous variables such as BMI and age were evaluated using the Wilcoxon rank-sum test, while categorical variables were assessed using Fisher's Exact Test and Chi-squared test. Results: Seventy-two patients were included in our analysis. Mean age and BMI were 56.3 ± 16.8 years and 32.3 ± 11.2, respectively. The majority of patients were female (69.4%) and white (83.8%). Approximately half of all patients had single positivity (64.4%) and more than half had detectable lupus anticoagulant (58.7%). Cardiolipin IgM was the most frequently (36.1%) elevated biomarker. Patient characteristics between the DOAC/aspirin and warfarin/enoxaparin cohorts were not significantly different; however, significantly more patients with single positivity received DOAC/Aspirin rather than warfarin/enoxaparin (77.8% vs.43.5%, p = 0.012). There was no statistically significant difference between the frequency of arterial complications in patients who took DOAC/Aspirin (4 events in 39 patients) versus those who took warfarin/enoxaparin (1 event in 33 patients), p = 0.366. The majority of arterial complications (4 of 5 events) occurred in patients with double and triple positivity. In addition, a logistical regression was performed regarding different characteristic effects on positivity level (single, double or triple laboratory positive), which found the presence of lupus anticoagulant had a significant association with higher likelihood of double/triple positivity (p = 0.048). Conclusion: This study provides potential reassurance for clinicians regarding the use of DOACs during the investigative phase of APLS and supports the continuation of DOAC therapy in patients, particularly those with single positivity, after careful evaluation and shared decision-making with patients. However, caution should be kept when considering DOAC use in patients with lupus anticoagulant, double, or triple positivity, due to concerning arterial events. Further large multi-center randomized clinical trials are necessary in the future to clarify the role of DOACs in APLS.

Direct Oral Anticoagulants for Stroke and Systemic Embolism Prevention in Patients with Left Ventricular Thrombus.

In recent years, direct oral anticoagulants (DOAC) have accumulated evidence of efficacy and safety in various clinical scenarios and are approved for a wide spectrum of indications. Still, they are currently used off-label for left ventricular thrombus owing to a paucity of evidence. For the same reason, there is a lack of guideline indication as well. Our work is based on an exhaustive analysis of the available literature and provides a structured and detailed update on the use of DOACs in patients with left ventricle thrombus. The safety and efficacy of DOACs were analyzed in particular clinical scenarios. As far as we know, this is the first paper that analyzes DOACs in this approach.

Is there still room for warfarin after the appearance of direct oral anticoagulants?

After the appearance of direct oral anticoagulants (DOAC), the use of vitamin K antagonists (VKA) has become more rare, but nevertheless, there are diseases in which they remain indispensable drugs. This review is devoted to VKA and the diseases in which these drugs can be used. The article compares the mechanism of action of VKA and DOAC, discusses methods of monitoring VKA therapy. Among the diseases of non-alternative use of VKA, mechanical prosthetic heart valves, atrial fibrillation in patients with moderate and severe mitral stenosis, antiphospholipid syndrome should be mentioned. Another indication for the appointment of anticoagulants is thrombosis of the left ventricle. In patients who have survived a myocardial infarction complicated by left ventricular thrombosis, anticoagulant treatment should be continued for up to 6 months with repeated imaging control. For this purpose, warfarin is successfully used. Currently, there is insufficient data to recommend the routine use of DOAC in patients with KrCl less than 25–30 ml/min, and in routine practice, warfarin remains the main anticoagulant in such patients. Direct oral anticoagulants have practically not been studied in the so-called special groups of patients: patients with congenital thrombophilia and rare localizations of thrombosis. There were practically no such patients in randomized trials and very little is known about the effectiveness of DOAC, so today warfarin remains the main drug for their treatment. Despite the fact that DOAC has displaced VKA in patients with non-valvular AF, we should not forget that it is VKA that we are obliged to prove the effectiveness of anticoagulants in patients with AF. The article discusses the pharmacogenetics of warfarin in relation to the data of the Russian Federation, as well as the practically important question of the possibility of resuming anticoagulants in patients with bleeding, the results of their own research are presented.

Effectiveness and Safety of Direct Oral Anticoagulants Among Patients with Non-valvular Atrial Fibrillation and Multimorbidity.

In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs). Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January1, 2012 to December31, 2017 was conducted. High multimorbidity was classified as having ≥ 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard ratios of S/SE and MB among three 1:1 propensity score matched DOAC cohorts. All-cause healthcare costs were estimated using generalized linear models. Overall 36% of the NVAF study population had high multimorbidity, forming three propensity score matched (PSM) cohorts: 12,511 apixaban-dabigatran, 60,287 apixaban-rivaroxaban, and 12,567 dabigatran-rivaroxaban patients. Apixaban was associated with a lower risk of stroke/SE and MB when compared with dabigatran and rivaroxaban. Dabigatran had a lower risk of stroke/SE and a similar risk of MB when compared with rivaroxaban. Compared to rivaroxaban, apixaban patients incurred lower all-cause healthcare costs, and dabigatran patients incurred similar all-cause healthcare costs. Compared to dabigatran, apixaban patients incurred similar all-cause healthcare costs. Patients with NVAF and ≥ 6 comorbid conditions had significantly different risks for stroke/SE and MB when comparing DOACs to DOACs, and different healthcare expenses. This study's results may be useful for evaluating the risk-benefit ratio of DOAC use in patients with NVAF and multimorbidity.

Predictors of use of direct oral anticoagulants in acute pulmonary embolism.

In the last decade, direct oral anticoagulants (DOACs) have been incorporated as an anticoagulation tool in patients with acute pulmonary thromboembolism (PTE). Although they have a better pharmacological profile than vitamin K antagonists (VKA), the use of these drugs is not massive. The objective of this study was to evaluate the use of DOACs in patients with acute PE and to detect determinants of its use. Prespecified analysis of the CONAREC XX registry that included patients with acute PE in 64 centers in Argentina. An analysis was performed to detect predictors of DOAC prescription at discharge. 579 patients who received anticoagulation at hospital discharge were analyzed: 60% received VKA, 21% heparin and 19% DOAC (of them, 49% Rivaroxaban, 34% Apixaban, and 17% Dabigatran). Patients receiving DOACs had less severe PE, lower risk of bleeding, and fewer in-hospital complications. At 30-day follow-up, there were no differences in all-cause mortality or bleeding. Health coverage by social insurance (OR 7.45, CI 95% 1.74-31.9, p < 0.01) or by private coverage (OR 10.5, CI 95% 2.4-45.9, p < 0.01) were independent predictors of DOAC prescription at discharge, and history of heart failure (OR 0.19, 95% CI 0.04-0.84, p = 0.028) and oncological disease (OR 0.49, 95% CI 0.27-0.89; p = 0.02) were predictors not prescribe them. One in five survivors of acute PE received DOACs at hospital discharge in Argentina, and this was determined by clinical and economic variables.

Direct Oral Anticoagulants Versus Warfarin for Venous Thromboembolism Prophylaxis in Patients With Nephrotic Syndrome: A Retrospective Cohort Study.

Evidence supporting venous thromboembolism (VTE) prophylaxis with direct oral anticoagulants (DOACs) in patients with nephrotic syndrome (NS) is limited to case reports. The purpose of this study was to compare bleeding and thromboembolic events in this population. A retrospective cohort study was conducted in adults with NS initiated on a DOAC or warfarin for VTE prophylaxis between January 2013 and July 2021 within the Ochsner Health System. Patients with study drug exposure within the preceding 7 days, acute VTE within the preceding 6 months, or ≤7 days of study drug exposure were excluded. The primary outcome was the composite rate of major bleeding and clinically relevant nonmajor bleeding. Secondary outcomes included time to major bleeding and rate of new thromboembolic events. This study was approved by the Ochsner Health System Institutional Review Board. Twenty-five DOAC and 19 warfarin patients were included. The primary outcome occurred in 8% vs 26.3% (P = 0.21) of patients treated with a DOAC or warfarin, respectively, and was driven by major bleeding (4% vs 21%, P = 0.25). Other secondary outcomes were similar between cohorts. The study was limited by a small sample size. Use of DOACs for VTE prophylaxis resulted in a nonstatistically significant, but clinically relevant lower rate of major bleeding compared to warfarin. This study provides comparative data showing safe and effective use of DOACs in patients with NS. Prospective, randomized studies are needed to confirm results.

Abstract TMP74: Direct Oral Anticoagulants Vs. Vitamin K Antagonists In Patients With Cerebral Venous Thrombosis: A Systematic Review And Meta-analysis

Introduction: Direct oral anticoagulants (DOACs) have emerged as a potential anticoagulant therapy for patients with cerebral venous thrombosis (CVT). We conducted a systematic review and meta-analysis comparing DOACs versus vitamin K antagonists (VKAs) for treatment of CVT. Methods: We registered the review in PROSPERO (registration number CRD42021228800). We searched Medline, Embase, CINAHL, and the Web of Science Core Collection from January 1, 2007, to May 26, 2021. We included randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) evaluating key outcomes for efficacy (recurrent venous thromboembolism [VTE] and complete recanalization) and safety (major hemorrhage). We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0 (for RCTs) and the ROBINS-I tool (for NRCSs). Where studies were sufficiently similar, we performed meta-analyses using random-effects models. This review was funded by Brown Neurology. Results: Of 8213 identified records,10 studies (1 RCT and 9 NRCSs) with a total of 662 patients (33% DOAC and 67% VKAs) met the inclusion criteria. We will present our risk of bias assessment at the conference. DOACs and VKAs had comparable efficacy: recurrent VTE (risk ratio [RR] 1.00, 95% confidence interval [CI] 0.44-2.23; I 2 =0%; 10 studies) and complete recanalization (RR 1.00, 95% CI 0.77-1.28; I 2 =0%; 6 studies). DOAC and VKA also had comparable safety: major hemorrhage (RR 0.89, 95% CI 0.37-2.14; I 2 =0%; 9 studies). Conclusions: Studies comparing DOACs with VKAs in patients with CVT consist mostly of small, non-randomized, poorly controlled studies. While the two treatments appear comparable for major efficacy and safety outcomes, large, rigorously conducted studies, preferably randomized, are needed to overcome these limitations and permit development of clinical practice guidelines for the use of DOACs in patients with CVT.

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.

Efficacy and safety of direct oral anticoagulants in morbidly obese patients with non-valvular atrial fibrillation: a systematic review and meta-analysis

Abstract Introduction Atrial fibrillation (AF) is the most common arrhythmia, with an estimated prevalence between 1–4%. On the other hand, obesity continued to be a prevalent health issue worldwide. Direct oral anticoagulants (DOACs) have been increasingly preferred over warfarin; however, The International Society of Thrombosis and Hemostasis (ISTH) recommended avoiding the use of DOACs in patients with a BMI &amp;gt;40 or weight &amp;gt;120 kg because of limited clinical data in these patients. In this meta-analysis, we aimed to evaluate the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. Method We performed a comprehensive literature search using multiple databases from database inception through January 2021, for all the studies that evaluated the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. The primary outcome of interest was stroke or systemic embolism (SSE) rate. The secondary outcome was major bleeding (MB). All meta-analyses were conducted using a random-effect model. Results A total of 10 studies including 89,494 morbidly obese patients (BMI &amp;gt;40 or weight &amp;gt;120 kg) with non-valvular AF on oral anticoagulation therapy (45427 on DOACs vs. 44067 on warfarin) were included in the final analysis. One included study was a randomized controlled trial (RCT), another study was a post hoc analysis of an RCT and the rest were retrospective cohort studies. The mean follow-up period was 1.8 years (range 8 months to 3.1 years). The SSE rate was significantly lower in DOACs group compared to warfarin group (odds ratio (OR): 0.71; 95% confidence interval (CI): 0.62, 0.81; p&amp;lt;0.0001; I2=0%). MB rate was also significantly lower in DOACs group compared to the warfarin group (OR 0.60, 95% CI 0.46–0.78, P&amp;lt;0.0001, I2=86%). Subgroup analysis in the rivaroxaban and apixaban AF cohort showed a statistically significant difference in SSE and MB event rates favoring both over warfarin therapy. Dabigatran showed non-inferiority to warfarin in SSE rate but superiority in the safety outcome. Conclusions Our meta-analysis demonstrated that DOACs are effective and safe when compared to warfarin in morbidly obese patients. However, more large scale randomized clinical trials are needed to further evaluate the efficacy and safety of DOACs compared to warfarin in this cohort of patients. Funding Acknowledgement Type of funding sources: None. Stroke and systemic embolism eventsMajor bleeding events

S1169 Efficacy and Safety of Direct Oral Anticoagulants for the Treatment of Portal Vein Thrombosis in Patients With Liver Cirrhosis

Introduction: Studies have reported direct oral anticoagulants (DOACs) to be as effective and safe as traditional anticoagulants (TACs) for portal vein thrombosis (PVT) treatment in cirrhotic patients. However, ideal management remains ambiguous with limited data. Our study was to compare efficacy and safety of DOACs to TACs in cirrhotic patients with PVT. Methods: This is an institutional review board approved, retrospective chart review of four teaching hospitals from January 1st, 2015 to March 31st, 2021. Treatment response and safety were compared in cirrhotic patients on DOACs versus TACs, such as warfarin or low-molecular weight heparin, for PVT. Patients were excluded if they had received anticoagulation for conditions other than PVT, aged < 18, or were pregnant or breastfeeding. Data collected included anticoagulation agent, therapy duration, Child-Turcotte-Pugh class (CTP), radiographic imaging, and adverse medication reactions. We evaluated (1) the rate of progression, non-progression or recanalization of PVT and (2) rate of major bleeding, defined by a hemoglobin drop of ≥ 2, transfusion requirement, or need for reversal antidote. All other events were classified as minor bleeding. Results: A total of 527 patients had PVT and cirrhosis. Ninety-seven patients were initiated on anticoagulation, 53 met study inclusion criteria, and 27 had completed follow-up imaging. Of these 27 patients, 7 were CTP class A, 16 were B, 1 was C, and 3 were unknown at treatment initiation. Ten were on TACs and the remaining 17 were on DOACs. Seven patients (70%) on TACs vs. 14 (82.4%) on DOACs had resolution of PVT, 3 patients (30%) on TACs vs. 1 (5.9%) on DOACs had non-progression of PVT, and 2 (11.8%) on DOACs progressed without recanalization. Six patients (60%) on TACs vs. 14 (82.4%) on DOACs had resolution of PVT within 9 months of anticoagulation initiation. Three out of 10 patients (30%) on TACs and 3 out of 17 patients (17.6%) on DOACs had major bleed. No patients had minor bleed. There was no difference between treatment groups with respect to time of major bleed occurrence. Conclusion: Our study showed that DOACs were effective and safe for the treatment of PVT in patients with cirrhosis. Resolution of PVT in cirrhotic patients appeared to be slightly higher, and bleeding events lower, in those on DOACs compared to those on TACs. Large, prospective studies are warranted to elucidate the optimal use of DOACs in patients with cirrhosis, particularly in CTP class C.

Safety and Efficacy of Direct Oral Anticoagulants in Patients With Moderate to Severe Cirrhosis.

Direct oral anticoagulants (DOACs) remain mostly investigational in patients with moderate to severe hepatic cirrhosis, yet are often selected over traditional anticoagulants including warfarin and enoxaparin in this setting. To determine the safety and efficacy of DOACs in patients with moderate to severe hepatic cirrhosis as compared with traditional anticoagulation. This was a retrospective, single-center cohort study evaluating inpatients and outpatients who were prescribed a DOAC, warfarin, or enoxaparin for therapeutic anticoagulation with Child-Turcotte-Pugh (CTP) B or C status at the time that the prescription was written. Included patients were followed until first bleeding or thromboembolic event, or until discontinuation of anticoagulation therapy. Data were collected by manual chart review. The primary outcomes included both bleeding events and thromboembolic events in the DOAC population as compared with traditional anticoagulation. A total of 101 patients were included in the study, 69 treated with DOAC therapy and 32 with traditional anticoagulation. Bleeding events occurred in 36% of patients in the DOAC group and 22% of patients in the traditional group (P = 0.149). In both groups, bleeds were most commonly gastrointestinal. Thromboembolic events occurred in 4% of the DOAC population and no patients in the traditional population (P = 0.55). No fatal bleeding or thromboembolic events occurred. DOACs do not appear to be more harmful than traditional anticoagulation in patients with CTP B or C status. These results support the use of DOACs in patients with CTP B or C hepatic cirrhosis when considering safety, efficacy, and convenience.

Use of Direct Oral Anticoagulants in Patients With Antiphospholipid Syndrome: A Systematic Review and Comparison of the International Guidelines.

Antiphospholipid antibody syndrome (APS) requires long-term anticoagulation to prevent recurrent thrombosis. Direct oral anticoagulants (DOACs) have been increasingly used in APS patients, but contradictory guidelines recommendations on their use do exist. We performed a systematic review of literature including studies investigating the role of DOACs in APS patients. At this aim, PubMed and Cochrane databases were searched according to PRISMA guidelines. We identified 14 studies which investigated the use of DOACs in patients with APS, of which 3 randomized clinical trials (RCTs), 1 post-hoc analysis of 3 RCTs, 7 case series and 3 cohort studies (2 prospective and 1 retrospective). Among DOACs, rivaroxaban was the most used (n = 531), followed by dabigatran (n = 90) and apixaban (n = 46). Regarding guidelines indications, the 2019 European Society of Cardiology (ESC) and American Society of Hematology (ASH) guidelines recommend against the use of DOACs in all APS patients. The European League Against Rheumatism (EULAR), British Society for Haematology (BSH), and International Society on Thrombosis and Haemostasis (ISTH) guidance provided more detailed indications stating that warfarin should be the first-choice treatment but DOACs may be considered in patients (1) already on a stable anticoagulation with a DOAC, (2) with low-quality anticoagulation by warfarin, (3) unwilling/unable to undergo INR monitoring, (4) with contraindications or serious adverse events under warfarin. Patients with arterial APS or triple positivity should be treated with warfarin while venous APS with single or double positivity may be candidate to DOACs, but high-quality studies are needed.

Thrombosis in myeloproliferative neoplasms: Treatment outcomes of direct oral anticoagulants and vitamin K antagonists

BackgroundPatients with myeloproliferative neoplasms (MPNs), such as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are at an increased risk of recurrent thromboembolic events (TEs) and hemorrhagic complications. Anticoagulation with vitamin K antagonists (VKAs) had been the standard of care until the recent US Food and Drug Administration approval of direct oral anticoagulants (DOACs) for treatment of cancer‐associated thrombosis. However, since patients with MPNs were underrepresented in large studies, the use of DOACs in patients with MPN‐associated thrombosis remains understudied. ObjectivesThe primary objective of this study was to establish the incidence of recurrent TEs and hemorrhagic complications in patients with MPN‐associated thrombosis treated with DOACs versus VKAs as first‐line therapy. MethodsData from 30 patients ≥18 years old with established diagnoses of PV or ET who were treated with either DOACs or VKAs as the first‐line anticoagulant for arterial and/or venous thrombosis were reviewed to determine the incidence of recurrent TEs as well as hemorrhagic complications. ResultsNineteen patients were treated with DOACs, and 11 were treated with VKAs. Of those on DOACs, 1 had a recurrent thrombosis, and 4 had bleeding events. Of the 11 patients treated with VKAs, 1 had a recurrent thrombotic event, and 1 had a bleeding event. ConclusionOur data did not demonstrate a significant difference in recurrent TEs or bleeding events in patients with MPN‐associated thrombosis anticoagulated with either DOACs or VKAs.

Adverse Events in Patients with Cancer Treated with Direct Oral Anticoagulants and Cancer Therapy

IntroductionFour direct oral anticoagulants (DOAC) have been approved for the treatment of venous thromboembolism VTE and prevention of stroke in patients with non-valvular atrial fibrillation (NVAF) in the USA: rivaroxaban, apixaban, edoxaban and dabigatran. Data regarding efficacy and safety of DOAC in the cancer population however are currently limited to very small cohorts in the large randomized trials for treatment of VTE in which many cancer patients did not meet eligibility requirements, or to retrospective studies and quality improvement initiatives. Despite major consensus guidelines recommending low molecular weight heparin (LMWH) as the preferred treatment for cancer-associated VTE, DOAC are commonly prescribed for cancer patients in both community and academic settings. Data on the safety and efficacy of DOAC in patients getting active cancer treatment are lacking. We aimed to characterize the use of DOAC in patients managed at an academic comprehensive cancer center, to examine the incidence of thrombotic and bleeding events among patients receiving active cancer therapy during the study period.MethodsFollowing IRB approval, a retrospective chart review was performed in patients treated at an academic comprehensive cancer center. Patients >18 years old who had a prescription written for a DOAC between June 2015 and December 2016 were identified. Patients were included if they were receiving DOAC for NVAF, acute VTE, and secondary prevention and had active cancer. Patients were assessed for baseline demographics, indications for anticoagulation, DOAC management strategies, arterial and venous thrombotic events and bleeding complications during treatment with DOAC. Descriptive statistics were used to analyze study outcomes.ResultsOf the 721 patients screened, 392 were patients with cancer of which 241 s were actively being treated with chemotherapy while on DOAC. The other 151 patients were not actively receiving treatment. VTE was the most common indication for DOAC use in 75% of cancer patients (n=297), followed by NVAF in20% (n=78). There were 15 patients with history of both NVAF and VTE, and 2 patients with TIA. Apixaban was used in 48% of patients; rivaroxaban in 47%; dabigatran in 4%, and edoxaban < 1%.Of the 392 evaluated cancer patients, 15 (3.83%) experienced thrombotic events with 11/15 new or recurrent VTE, 3/15 stroke, and 1/15 myocardial infarction while on DOAC. The VTE rate was strikingly higher in those patients receiving active cancer treatment at 4.15% compared to 0.66% in those not getting treatment. The rate of major bleeding and clinically overt bleeding was not different between the 2 groups and was approximately 4.5%. (table 1)ConclusionWe found in our retrospective analysis of DOAC use in cancer patients, that patients getting active cancer treatment had higher rates of primarily venous and arterial thrombotic events while treated with DOAC compared to those patients not getting active cancer treatment. The rate of VTE at 4.14% compares favorably with published rates for VTE recurrence for LMWH and VKA in randomized controlled trials and is roughly 7 times higher than the rate in our patients with cancer treated with DOAC but not getting active cancer treatment. Despite differences in rates of thrombotic events, the bleeding rates were the same, and also comparable to published rates, confirming the known increased risk of bleeding in cancer patients. While our results are promising, dedicated randomized controlled trials comparing DOAC to LMWH are required to truly determine the efficacy and safety of DOAC in cancer patients simultaneously receiving cancer treatment. [Display omitted] DisclosuresConnors:BMS: Consultancy, Other: Scientific Advisory Board; Pfizer/BMS -Alliance: Other: Independent review committe; Unum Therapeutics: Other: Data Safety Monitoring Board; boehringer Ingelheim: Other: Scientific Advisory Board.

Oral Anticoagulant Dosing, Administration, and Storage: A Cross-Sectional Survey of Canadian Health Care Providers

Background: Direct oral anticoagulant (DOAC) use is increasing worldwide. However, if not taken or prescribed correctly, DOACs have serious side effects. It is crucial that healthcare providers (HCPs) provide patients with accurate information and counselling around DOACs, to optimize safe and effective use.Aims: To assess HCPs' knowledge about oral anticoagulant indication, dosing, storage, and administration.Methods: An electronic survey was distributed to HCPs across Canada from June to July 2017, with 18 questions on oral anticoagulant practical use.Results: A total of 73 responses were received: 27 (37%) from Hematologists, 4 (5.4%) from Thrombosis Medicine specialists, 17 (23.3%) from nurse practitioners, 17 (23.3%) from pharmacists, and 8 (11%) from residents and fellows in Hematology training programs across Canada. The median duration of practice was 7 years (range 0.5 to 41). The majority of respondents (64 of 73; 88%) worked in the outpatient setting. Only 18 (25%) of the respondents correctly identified all the approved indications for warfarin and 4 DOACs including dabigatran, rivaroxaban, apixaban, and edoxaban. Most of the respondents (54 of 73; 74%) correctly identified that DOACs are not approved for treatment of heparin induced thrombocytopenia, cerebral sinus venous thrombosis, or mechanical prosthetic valves. However, 11 (15%) cited one or more of the above indications incorrectly; 7 of 11 (9.5%) alarmingly chose mechanical prosthetic valves as an indication for DOACs. Most of the respondents (51 of 73; 70%) felt comfortable or very comfortable prescribing oral anticoagulants. When counselling patients, 69 (95%) discussed the indication and bleeding side effects, 62 (85%) discussed when/how to take the drug, and only 37 (51%) discussed adherence and administration strategies. About two thirds of the respondents (63%) knew that dabigatran should not be crushed, however only 38 (52%) knew that it should not be exposed to moisture. Forty-five of the respondents (62%) knew that higher dose rivaroxaban should be taken with food. While 45 (62%) correctly adjusted the dose of apixaban based on age, only 35 (48%) did the same for dabigatran. 80%, 77%, 70%, and 45% correctly adjusted rivaroxaban, apixaban, dabigatran, and edoxaban, respectively for renal function.Conclusions: Although the majority of respondents expressed comfort with oral anticoagulants, there are important knowledge gaps around HCPs' practical understanding of oral anticoagulants, particularly in correctly identifying approved indications and counselling patients on adherence and administration. These knowledge gaps (e.g., inappropriate DOAC use in patients with mechanical valves) may lead to significant patient harm in the form of thrombosis or bleeding. Future research should focus on educational interventions to improve HCPs' knowledge around oral anticoagulants, with the goal of enhancing patient safety.Figure 1. What do health care providers counsel patients about when prescribing oral anticoagulants? [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Use of Direct Oral Anticoagulants in Inherited Thrombophilia

Introduction: Factor V Leiden mutation and prothrombin G20210A mutation are the most common causes of an inherited thrombophilia and together account for 50 to 60 percent of diagnoses. Traditionally, patients have been treated with oral warfarin therapy or injectable low molecular weight heparin (LMWH), which requires frequent laboratory monitoring or self-injections. The difficulty with administration and monitoring of traditional therapy has made direct oral anticoagulants (DOACs) increasingly favored for treatment of VTE. However, the efficacy and bleeding complication of DOAC use in inherited thrombophilia has not been well studied.Methods: We designed a retrospective analysis of patients with Factor V Leiden mutation and prothrombin G20210A mutation at the University of Virginia who were treated with a DOAC (rivaroxaban, apixaban, edoxaban, or dabigatran) for treatment of VTE or atrial fibrillation from January 28th, 2011 to May 30th, 2017. Adult patients with presence of either homozygous or heterozygous mutation for either Factor V Leiden mutation or prothrombin mutation were included. All patients were required to be treated for at least 48 hours with a documented follow-up of adverse events. Medical charts were reviewed for age, gender, weight, presence of Factor V Leiden mutation and/or prothrombin G20210A mutation, DOAC dose, and frequency, bleeding events, and recurrent thrombotic events. Our primary outcomes were efficacy defined as development of a recurrent VTE and safety defined as occurrence of any bleeding event. Efficacy was compared to the post-hoc sub-group analysis that was conducted on the data from the RE-MEDY trial, in which VTE/VTE-related deaths were observed to be 1.5% with patients taking dabigatran compared to 2.3% with patients taking warfarin (p=0.2277) (Skelley, et al. J Throm Thrombolysis, 2017). Major and minor events were defined per International Society of Thrombosis and Hemostasis (ISTH) anticoagulation committee guidelines.Results: Fifty eight patients were eligible for analysis. The median age was 52.7 ± 16.7 years with 39 (67.2%) females. Baseline patient characteristics, type of thrombophilia, and indication for DOAC therapy are represented in Table 1. Median length of time on a DOAC was 24 months.Four patients developed a recurrent VTE however on further analysis, 3 patients were found to be non-compliant with DOAC therapy. Excluding the noncompliant patients, the rate of a recurrent VTE was 1.7% (Table 2).Nine (15.5%) patients suffered a bleeding event, of which 4 were major and 5 were minor (Table 2). Of the 4 major bleeding events, 3 were gastrointestinal (GI). One patient bled due to arterio-venous malformations, the second patient developed a bleed at the esophagectomy site, and the third patient had biliary drainage from ischemic liver disease post liver transplant. One patient suffered an intracranial hemorrhage; this patient was concurrently taking aspirin and clopidogrel while on therapeutic apixaban. The minor bleeding events included epistaxis (n=1), hemoptysis (n=1) and GI (n=3). Hemoptysis was discovered simultaneously with the diagnosis of lung cancer. Three of the patients with minor bleeding events were taking ASA, including one who was also taking dual antiplatelet therapy with clopidogrel.Conclusion: DOACs have been shown to have similar efficacy and safety compared to warfarin in many patient populations. However, there are limited studies evaluating use of DOACs in patients with inherited thrombophilia. Substantial evidence supporting widespread DOAC use in these patients is lacking. Our study confirmed the efficacy of DOACs in this patient population with a thrombosis event of only 1.7% which is favorable compared to the warfarin historical control rate of 2.3% (Skelley, et al. J Throm Thrombolysis, 2017). There was a higher than expected rate of bleeding complications, however many patients were on dual antiplatelet therapy or had other risk factors for bleeding. It would be imprudent to attribute these bleeding events solely to DOAC use. Though this is the only study of its kind, it is limited by small numbers and retrospective design. Further studies are needed to evaluate the use of DOACs compared to warfarin and LMWH. We plan to conduct further analysis utilizing a control group of inherited thrombophilia patients on warfarin compared to those on DOACs. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Comparison of the Efficacy and Safety of Direct Oral Anticoagulants and Vitamin K Antagonists in Patients with Atrial Fibrillation and Concomitant Liver Cirrhosis: A Systematic Review and Meta-Analysis.

Patients with atrial fibrillation (AF) have a higher risk of developing thromboembolic events. Current guidelines recommend the use of oral anticoagulants for stroke prevention in these patients. Several clinical trials demonstrated that direct oral anticoagulants (DOACs) have similar efficacy and are safer alternatives to traditional oral anticoagulants. However, patients with concomitant liver cirrhosis were excluded from these trials. We aimed to systematically identify and review published clinical studies on the use of DOACs in patients with AF and liver cirrhosis and assess the efficacy and safety of DOACs in these patients. A systematic review of clinical trials and retrospective studies was conducted by searching the PubMed, Cochrane Library, Embase, SCOPUS, and Web of Science databases up to September 2020. Three retrospective studies were included, involving 4011 patients with AF and liver cirrhosis. The use of DOACs was associated with a significant reduction in ischemic stroke (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.42-0.90; p = 0.01), major bleeding events (HR 0.64; 95% CI 0.57-0.72; p < 0.001), and intracranial hemorrhage (HR 0.49; 95% CI 0.40-0.59; p < 0.001). Compared with warfarin in patients with AF and liver cirrhosis, DOACs appear to be associated with improved efficacy and safety outcomes. Randomized controlled trials are warranted to confirm these findings.

Clinical Evidence for the Choice of the Direct Oral Anticoagulant in Patients with Atrial Fibrillation According to Creatinine Clearance.

Atrial fibrillation (AF) often coexists with chronic kidney disease (CKD), which confer to the patient a higher risk of both thromboembolic and hemorrhagic events. Oral anticoagulation therapy, nowadays preferably with direct oral anticoagulants (DOACs), represents the cornerstone for ischemic stroke prevention in high-risk patients. However, all four available DOACs (dabigatran, apixaban, rivaroxaban and edoxaban) are eliminated by the kidneys to some extent. Reduced kidney function facilitates DOACs accumulation and, therefore, different dose reductions are required, with slight differences between American and European recommendations especially in case of severe renal impairment (creatinine clearance < 30 mL/min). Overall, the use of DOACs in patients with non-end stage CKD and AF is effective similarly to warfarin, showing a better safety profile. The management of thromboembolic risk among patients with AF on dialysis remains challenging, as warfarin effectiveness for stroke prevention in this population is questionable and retrospective data on apixaban need to be confirmed on a larger scale. In kidney transplant recipients, DOACs may provide a potentially safer option compared to warfarin, but co-administration with immunosuppressants is a matter of concern.