Abstract MP13: Comparative Effectiveness of Direct Oral Anticoagulants and Warfarin on Risk of Bleeding Resulting in Hospitalization Among Venous Thromboembolism Patients

Background: Direct oral anticoagulants (DOACs), including rivaroxaban, dabigatran, apixaban and edoxaban, have been approved as alternatives to warfarin for the primary treatment of venous thromboembolism (VTE). However, understanding of their comparative effectiveness in practice-based populations is limited. Objective: Among anticoagulant-naïve VTE patients, estimate the association of type of oral anticoagulant (OAC) with the rate of bleeding resulting in hospitalization. Methods: Patients with VTE and prescription for an OAC were identified from the US Truven Health MarketScan® Commercial and Medicare Supplemental databases for the period from 2011-2015. Hospitalization related to bleeding events (inclusive of intracranial, gastrointestinal and other) was defined using a validated algorithm. In head-to-head comparisons, initiators of a specific OAC were matched with up to 5 initiators of the comparing OAC by age, sex, and time since database enrollment. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) for bleeding by OAC, adjusted for age, sex, and a comorbidity propensity score (created using prevalence of 20 common diagnoses and procedures). Results: The final analysis included 83,831 VTE patients who were 49.9% female and on average (standard deviation) 59.0 (16.0) years old. Of these, the initial OAC prescribed for 2,604 was apixaban, for 1,669 dabigatran, for 28,518 rivaroxaban, and for 48,514 warfarin. A total of 1,947 bleeding events occurred over an average of 13 months. Compared to new warfarin users, risk of bleeding was lower among patients initiating apixaban [HR (95%CI): 0.55 (0.36, 0.83)] and rivaroxaban [0.80 (0.72, 0.89)], but similar among new dabigatran users [0.96 (0.72, 1.27)]. In head-to-head DOAC comparisons, relative to rivaroxaban, risk of bleeding was lower among users of apixaban [0.57 (0.36, 0.89)] but similar for users of dabigatran [1.05 (0.73, 1.51)]. Due to low numbers we did not conduct analyses of edoxaban or a head-to-head comparison of dabigatran versus apixaban. Conclusion: In this practice-based population of 83,831 patients prescribed OACs for the treatment of VTE, subsequent risk of hospitalized bleeding was lowest among those prescribed apixaban, intermediate among those prescribed rivaroxaban, and highest among those prescribed warfarin and dabigatran. These data demonstrate that differences in bleeding risk exist by DOAC. While risk factors for bleeding might impact choice of warfarin versus the DOACs, the choice between DOACs may be less likely to be based on patient conditions.

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Risks and Benefits of Direct Oral Anticoagulants across the Spectrum of GFR among Incident and Prevalent Patients with Atrial Fibrillation

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.13811217 ◽

2018 ◽

Vol 13 (8) ◽

pp. 1144-1152 ◽

Cited By ~ 17

Author(s):

Jung-Im Shin ◽

Alex Secora ◽

G. Caleb Alexander ◽

Lesley A. Inker ◽

Josef Coresh ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Oral Anticoagulant ◽

Proportional Hazards ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Cox Proportional Hazards ◽

Direct Oral Anticoagulant ◽

Bleeding Events ◽

Risk Of Bleeding

Background and objectivesAll randomized trials of direct oral anticoagulants in atrial fibrillation excluded patients with severe kidney disease. The safety and effectiveness of direct oral anticoagulants across the range of eGFR in real-world settings is unknown. Our objective is to quantify the risk of bleeding and benefit of ischemic stroke prevention for direct oral anticoagulants compared with warfarin in patients with atrial fibrillation with and without CKD.Design, setting, participants, & measurementsWe created a propensity score–matched cohort of 3206 patients with atrial fibrillation and direct oral anticoagulant use and 3206 patients with atrial fibrillation using warfarin from October of 2010 to February of 2017 in an electronic health record (Geisinger Health System). The risks of bleeding and ischemic stroke were compared between direct oral anticoagulant and warfarin users using Cox proportional hazards regression, stratified by eGFR (≥60 and <60 ml/min per 1.73 m2).ResultsThe mean (SD) age of the 6412 participants was 72 (12) years, 47% were women, and average eGFR was 69 (21) ml/min per 1.73 m2. There were 1181 bleeding events and 466 ischemic strokes over 7391 person-years of follow-up. Compared with warfarin use, the hazard ratios (HRs) (95% confidence interval [95% CI]) of bleeding associated with direct oral anticoagulant use were 1.01 (0.88 to 1.17) and 1.23 (1.02 to 1.48) for those with eGFR≥60 and eGFR<60 ml/min per 1.73 m2, respectively (P-interaction=0.10). There was no difference between direct oral anticoagulant and warfarin users in the risk of ischemic stroke: HRs (95% CI) of 0.94 (0.74 to 1.18) and 1.02 (0.76 to 1.37) for those with eGFR≥60 and eGFR<60 ml/min per 1.73 m2, respectively (P-interaction=0.70). Similar findings were observed with individual drugs.ConclusionsIn a large health care system, patients with eGFR<60 ml/min per 1.73 m2 who took direct oral anticoagulants for atrial fibrillation had slightly higher risk of bleeding compared with those on warfarin, but similar benefits from prevention of ischemic stroke.

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Contrasts in Glioblastoma—Venous Thromboembolism versus Bleeding Risk

Cells ◽

10.3390/cells10061414 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1414

Author(s):

Viktoria Muster ◽

Thomas Gary

Keyword(s):

Venous Thromboembolism ◽

Patient Group ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Bleeding Events ◽

Therapeutic Anticoagulation ◽

Vulnerable Patient ◽

Risk Treatment ◽

Thrombogenic Potential

Glioblastoma is among the tumor entities with an extreme thrombogenic potential and patients are at very high risk of developing a venous thromboembolism (VTE) over the course of the disease, with an incidence of up to 30% per year. Major efforts are currently being made to understand and gain novel insights into the underlying pathomechanisms of the development of VTE in patients with glioblastoma and to find appropriate biomarkers. Yet, patients with glioblastoma not only face a high thromboembolic risk but are also at risk of bleeding events. In the case of VTE, a therapeutic anticoagulation with low molecular weight heparin or, in the case of low bleeding risk, treatment with a direct oral anticoagulant, is recommended, according to recently published guidelines. With respect to an elevated bleeding risk in glioblastoma patients, therapeutic anticoagulation remains challenging in this patient group and prospective data for this vulnerable patient group are scarce, particularly with regard to direct oral anticoagulants.

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Effectiveness and safety of oral anticoagulants in the treatment of acute venous thromboembolism: A nationwide comparative cohort study in France

Thrombosis and Haemostasis ◽

10.1055/a-1731-3922 ◽

2022 ◽

Author(s):

Laurent Bertoletti ◽

Gaelle Gusto ◽

Artak Khachatryan ◽

Nadia Quignot ◽

Jose Chaves ◽

...

Keyword(s):

Venous Thromboembolism ◽

Propensity Score ◽

Conventional Therapy ◽

Proportional Hazards ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

All Cause Mortality ◽

Recurrent Vte

Introduction: Data from clinical trials indicate that direct oral anticoagulants (DOACs) are non-inferior 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. Materials and 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 2013–2018. 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: 58137 patients were included (10775 VKAs, 10440 apixaban, 36922 rivaroxaban). Propensity score-matched cohort sizes were 7503 for apixaban and 9179 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]). Conclusions: 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.

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Treatment Patterns and Clinical Outcomes in Korean Cancer Patients With Venous Thromboembolism: A Retrospective Cohort Study

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620979575 ◽

2021 ◽

Vol 27 ◽

pp. 107602962097957

Author(s):

Soo-Mee Bang ◽

Jin-Hyoung Kang ◽

Min Hee Hong ◽

Jin-Seok Ahn ◽

So Yeon Oh ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Clinical Outcomes ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Events ◽

Factors Associated ◽

Vein Thrombosis ◽

Medical Chart Review ◽

Deep Vein

This study assessed epidemiologic data and clinical outcomes, including venous thromboembolism (VTE) recurrence and bleeding events, in patients with cancer-associated VTE, and assessed factors associated with clinical outcomes. Data were extracted from retrospective medical-chart review of adult patients diagnosed with cancer-associated deep vein thrombosis or pulmonary embolism who received anticoagulation treatment for ≥3 months. Patients were classified by: low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOACs), and other anticoagulants. First VTE recurrence and bleeding events, and factors associated with their occurrence, were assessed during the initial 6 months of treatment. Overall, 623 patients (age: 63.7 ± 11.3 years, 49.3% male) were included (119, 132, and 372 patients in LMWH, DOACs and other anticoagulants groups, respectively). The cumulative 6-month incidence of VTE recurrence was 16.6% (total), 8.3% (LMWH), 16.7% (DOACs), and 20.7% (other); respective bleeding events were 22.5%, 11.0%, 12.3%, and 30.7%). VTE recurrence and bleeding rates differed only between LMWH and other anticoagulants (HR 2.4, 95% CI: 1.2-5.0 and 3.6, 1.9-6.8, respectively). These results highlight the importance of initial VTE treatment choice for preventing VTE recurrence and bleeding events. LMWH or DOACs for ≥3 months can be considered for effective VTE management in cancer patients.

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The Risk of Bleeding in Patients Receiving Ibrutinib Combined with Novel Direct Oral Anticoagulants

Blood ◽

10.1182/blood-2019-125356 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4314-4314

Author(s):

Michal Ariela Raz ◽

Jon E. Arnason ◽

Osnat Bairey ◽

Lev Shvidel ◽

Ariel Aviv ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Lymphoproliferative Disorders ◽

Bleeding Events ◽

Concurrent Administration ◽

Risk Of Bleeding ◽

Grade 3

Introduction: Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase, is an established therapeutic agent in a variety of B-cell lymphoproliferative disorders. Ibrutinib induces platelet dysfunction and concurrent treatment with ibrutinib and warfarin was shown to significantly increase the risk of bleeding. The current study was designed to investigate the safety of direct oral anticoagulants (DOACs) in patients receiving ibrutinib, considering their expanding employment together with the lack of data regarding their safety in patients receiving ibrutinib. Methods: We conducted a retrospective cohort study to evaluate risks of major bleeding in patients with B-cell lymphoproliferative disorders (CLL, MCL, DLBCL, MZL or WM) that were treated with ibrutinib and DOACs but without concurrent antiplatelet therapy, between January 2010 and October 2018 in 5 participating centers. Patient medical charts were reviewed for demographic parameters, comorbidities, ibrutinib dosage, DOACs dosage (including the adjustment for renal function), blood count and chemistry tests, bleeding site and grade. Results: The study included 30 patients, median age at starting concurrent administration of ibrutinib and DOACs was 71.58 years (range 50.9-88.2). Most patients were treated for CLL (n=18, 60%) and MCL (n=8, 26%). The most common daily doses of ibrutinib were 420 mg and 560 mg in 63.3% and 30% of patients respectively. None of the patients received an additional antiplatelet agent. Twenty-three patients were treated with apixaban (76.7%), 4 with rivaroxaban (13.3%) and 3 (10%) with dabigatran. The main indications for DOACs were atrial fibrillation and VTE (venous thromboembolism). The median follow-up after initiation of the ibrutinib-DOAC combination was 13.4 months (range 1.8-47.9 months). Bleeding was reported in 22 patients (73.3%), mostly mucocutaneous (n=12, 40%) and gastrointestinal tract (n=7, 23.3%), followed by CNS bleeding (n=4, 13.3%). Mucocutaneous bleedings were all grade 1-2 and gastrointestinal tract and CNS bleeding events were grade 1-4. Major bleeding events, defined as grade 3 or 4, occurred in 5 patients (16.6%) and did not result in death of any of the patients. The median time for bleeding following ibrutinib-DOAC initiation was 5.6 months. Over a follow-up period of 21 months of combined treatment, the incidence of bleeding events (of all grades) increased to 75% (Figure 1). Incidence of bleeding events (including all grades) was quite similar between all DOAC subtypes (73.9% with apixaban, 75% with rivaroxaban and 66.7% with dabigatran). No statistically significant predictors for increased risk of bleeding in patients receiving ibrutinib combined with DOACs were detected. Ibrutinib was stopped in 8 patients (26.7%) due to grade 1 to 4 bleeding events and was re-initiated in 6 patients, resulting in recurrent grade 3 and 4 bleeding events in 2 patients. Conclusions: Concurrent administration of DOACs and ibrutinib appears to be feasible. However, risk of bleeding is not neglectable, and treatment resumption in patients that experienced a significant bleeding event should be considered with caution. Disclosures Arnason: Celgene/Juno: Consultancy; Regeneron Pharmaceuticals, Inc.: Consultancy. Herishanu:Roche: Honoraria; AbbVie: Honoraria; Janssen: Honoraria.

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Bleeding Risk in Non-Valvular Atrial Fibrillation Patients Receiving Direct Oral Anticoagulants and Warfarin: A Systematic Review and Meta-Analysis of Observational Studies

Blood ◽

10.1182/blood-2019-123870 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3672-3672 ◽

Cited By ~ 1

Author(s):

Yimin Pearl Wang ◽

Rohan Kehar ◽

Alla Iansavitchene ◽

Alejandro Lazo-Langner

Keyword(s):

Major Bleeding ◽

Lower Risk ◽

Observational Studies ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Bleeding Risk ◽

Risk Of Bleeding ◽

Significant Difference

Introduction: The standard oral anticoagulant therapy administered to non-valvular AF patients has typically been Vitamin K Antagonists (VKA) particularly warfarin. In recent years, Direct Oral Anticoagulants (DOACs) including Direct Thrombin Inhibitors (DTI) and Direct Factor Xa inhibitors (FXa inhibitors) have become an alternative to warfarin. Randomized trials comparing warfarin and DOACs showed comparable effectiveness without significant additional major bleeding risk. However, bleeding events in RCTs may differ from those in daily use due to the routine exclusion of patients with a higher risk of bleeding from many studies. We aimed to assess bleeding risk between DOACs and warfarin in AF patients in observational studies and we also sought to determine differences between patients that were experienced or naïve to oral anticoagulants. Methods: A systematic literature search was conducted in the OVID MEDLINE® and EMBASE® electronic databases. Observational studies and randomized control trials (RCT) from 1990 to January 2019 were retrieved and examined by two independent reviewers. A pooled effect hazard ratio (HR) was calculated using a random effects model using the generic inverse variance method. Subgroup analyses according to previous exposure to anticoagulants, study type, funding type and DOAC type were conducted. The primary outcome was major bleeding risk. The secondary outcome was clinically relevant non-major bleeding. All studies must have used an established or validated definition of major bleeding. Results: The initial literature search identified 3359 potentially eligible citations. After primary screening, 150 articles were eligible for full text review and there were 35 studies including 2,356,201 patients that met the inclusion criteria. Overall, patients on DOACs were less likely to experience a bleeding event compared to warfarin (HR 0.78, 95%CI 0.71, 0.85, P<0.001). The results were consistent when analyzing patients receiving DTIs or FXa inhibitors (DTI: HR 0.76, 95% CI 0.67,0.87; FXa inhibitors: HR 0.79, 95% CI 0.69,0.89). However, among patients receiving factor Xa inhibitors, there was a significant difference in the risk of bleeding according to individual drug. Among patients receiving rivaroxaban the risk of bleeding was similar to warfarin (HR 0.98, 95%CI 0.91,1.06, p=0.60) whereas in those receiving apixaban there was a 40% reduction in the risk of bleeding compared to warfarin (HR 0.60, 95%CI 0.50,0.71, p<0.001) (Figure 1). Three studies reported information according to previous anticoagulant exposure. The overall pooled hazard ratio was 0.68 (95% CI 0.55, 0.82 p<0.001) in favor of patients on DOACs. In the subgroup analysis of previous anticoagulant use, the risk of bleeding was lower for DOACs compared to warfarin in both the experienced population (HR 0.70, 95%CI 0.51, 0.96) and the naïve population (HR 0.64, 95% CI 0.47,0.87). However, heterogeneity was moderate to high among both subgroups. Conclusion: This review and meta-analysis of observational studies including over 2.3 million patients showed that overall DOACs have a lower risk of major bleeding and clinically relevant non-major bleeding compared to warfarin. Most importantly, although the pooled effect estimate did not differ between DTIs and FXa inhibitors, among patients receiving FXa inhibitors there was a significant difference between individual agents. Patients on apixaban had a significantly lower risk of bleeding compared to warfarin in contrast to patients on rivaroxaban who had a similar risk. Disclosures No relevant conflicts of interest to declare.

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Clinical Outcomes of Multiple Myeloma Patients Treated with Direct Oral Anticoagulants for Immunomodulatory Drug Associated Venous Thromboembolism

Blood ◽

10.1182/blood-2019-131396 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4964-4964 ◽

Cited By ~ 1

Author(s):

Zachary Crowther ◽

Jamie Doyle ◽

Stanford Taylor ◽

Nadia Ali

Keyword(s):

Multiple Myeloma ◽

Venous Thromboembolism ◽

Clinical Outcomes ◽

Chart Review ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Direct Result ◽

Bleeding Complications ◽

Bleeding Events ◽

Growing Body

Introduction: Venous thromboembolism (VTE) is a common complication in multiple myeloma (MM) patients for several reasons; hematologic malignancy itself is a VTE risk factor and standard of care immunomodulatory drugs (IMiDs) in combination with dexamethasone (Dex) increase the risk further. This combination therapy has a mean VTE incidence of 21.5% in studies that did not use thromboprophylaxis and is recommended for all patients on IMiDs, although the optimal thromboprophylactic regimen remains uncertain. In clinical practice, aspirin (ASA) is commonly prescribed for VTE prophylaxis due to the ease of use. Despite this, the incidence of VTE remains between 7-14%. There is a growing body of literature supporting the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of VTE in cancer populations. We wanted to assess the incidence of VTE despite ASA prophylaxis at our institution and to further characterize the role of DOACs in the MM population. To do this, we performed a chart review of all MM patients who had been treated with lenalidomide and a DOAC, assessing for VTE development and patient outcomes. Methods: We conducted a retrospective chart review of patients with the diagnosis of MM treated with lenalidomide therapy at Fox Chase Cancer Center at Temple University Hospital or Cottman Avenue after Jan 1st, 2015 to July 2019. Eligible patients were identified through electronic medical record data mining for patients that had been diagnosed with MM, had been prescribed lenalidomide, had been taking ASA while on lenalidomide, and switched to rivaroxaban, edoxaban or apixaban. For comparison, the number of patients treated with lenalidomide and ASA who did not switch to a DOAC were also identified. Patient charts were reviewed for VTE development and bleeding complications after DOAC administration. Results: 132 patients were identified who had a diagnosis of MM and had been prescribed lenalidomide between Jan 1, 2015 and July 31, 2019. These patients were also prescribed aspirin except for three who were already on a DOAC prior to starting lenalidomide. Of the total 132 patients, only 17 were prescribed a DOAC. Six of the patients were on DOACs for reasons other than VTE (atrial fibrillation N=4, atrial flutter N=1, marantic endocarditis N=1). Eleven patients were started on DOACs for VTE; incidence of 8.3% in our myeloma population. However three of these VTEs occurred within one month of high dose melphalan chemotherapy and autologous stem cell rescue. These three patients had been off lenalidomide for over one month prior to VTE. Eight of the 17 patients with VTE developed clots in the setting of active MM and concurrent therapy with IMiD/Dex, independent of hospitalizations or other provoking factors. This is an incidence of 6.0% for VTE directly attributed to therapy. Six patients were on lenalidomide and Dex, while two patients developed VTE while on pomalidomide and Dex. No patients on lenalidomide experienced recurrent VTEs after being switched to therapeutic dose DOAC. One patient on pomalidomide/Dex did experience recurrent VTE. We examined all 17 patients who were on DOACs, 16 of which had been on IMiD and DOACs concurrently. Three had minor bleeding events which all resolved spontaneously. One patient had a major bleeding event, which was a fatal ruptured cerebral aneurysm while on a DOAC and ASA concurrently. Conclusion: The incidence of VTE in our patient population receiving IMiD/Dex while on ASA prophylaxis therapy was similar to what has been previously reported in the literature. We examined the clinical outcomes of 16 patients treated with IMiDs and DOACs concurrently and found few bleeding events. The one major bleed was likely precipitated by malignant hypertension and not a direct result of being on a DOAC. Taken together these results further support the growing body of evidence that DOACs are effective and safe treatments for VTE in cancer patients, including MM. Moving forward, our clinical experience with treatment dose DOACs supports the use of prophylactic dose DOACs to potentially further reduce the incidence of VTE in this high-risk population. Disclosures No relevant conflicts of interest to declare.

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Abstract 15396: Atrial Fibrillation Bleeding Risk and Prediction While Treated With Direct Oral Anticoagulants in Warfarin Naïve and Experienced Patients

Circulation ◽

10.1161/circ.142.suppl_3.15396 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Alexander C Perino ◽

Krishna Pundi ◽

Jun Fan ◽

Susan K Schmitt ◽

Mitra Kothari ◽

...

Keyword(s):

Atrial Fibrillation ◽

Warfarin Therapy ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Risk Of Bleeding ◽

Warfarin Treatment ◽

Treatment Analysis ◽

Using Data ◽

Favorable Safety

Introduction: Direct oral anticoagulants (DOAC) are guideline-recommended over warfarin for stroke prevention in atrial fibrillation (AF). However, patients who are DOAC eligible are commonly maintained on warfarin. We sought to evaluate bleeding risk and prediction while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin. Methods: We performed a retrospective cohort study using data from the Veteran Affairs health care system. We included patients with a prescription for warfarin and/or DOAC from 10/1/2010 to 9/30/2017 with an AF encounter in the 90 days prior to 30 days after prescription. We categorized DOAC treated patients as warfarin-naïve or -experienced and performed an on-treatment analysis to determine bleeding incidence and HAS-BLED score discrimination. In adjusted analyses, we compared risk of bleeding while treated with DOAC (both for warfarin-naïve and -experienced patients) to warfarin. Results: The analysis cohort included 99,143 patients treated with warfarin (71±10 years, HAS-BLED 2.6±1.2) and 73,732 and 26,760 patients treated with DOAC who were warfarin-naïve (74±10 years, HAS-BLED 2.4±1.0) and -experienced (71±9 years, HAS-BLED 2.8±1.1), respectively. DOAC patients with warfarin experience had more prior bleeds (DOAC, warfarin-experienced: 11.9%; DOAC, warfarin-naïve: 4.5%; warfarin: 6.2%; p<0.001 for both). Risk of intracranial bleeding was substantially lower while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin ( Table ). HAS-BLED discrimination for bleeding outcomes, intracranial or any bleeding, was modest ( Table ). Conclusion: DOAC treatment had a favorable safety profile compared to warfarin treatment, even for DOAC treated patients with warfarin-experience who had more prior bleeds. These data argue against maintaining DOAC eligible patients on warfarin therapy regardless of HAS-BLED score.

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Comparative clinical outcomes between direct oral anticoagulants and warfarin among elderly patients with non-valvular atrial fibrillation in the CMS medicare population

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-019-01838-5 ◽

2019 ◽

Vol 48 (2) ◽

pp. 240-249 ◽

Cited By ~ 2

Author(s):

Alpesh Amin ◽

Allison Keshishian ◽

Oluwaseyi Dina ◽

Amol Dhamane ◽

Anagha Nadkarni ◽

...

Keyword(s):

Atrial Fibrillation ◽

Lower Risk ◽

Proportional Hazards ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Cox Proportional Hazards ◽

Cardiac Events ◽

Cox Proportional Hazards Models ◽

Medicare Patients ◽

Similar Risk

AbstractAtrial fibrillation (AF) prevalence increases with age; > 80% of US adults with AF are aged ≥ 65 years. Compare the risk of stroke/systemic embolism (SE), major bleeding (MB), net clinical outcome (NCO), and major adverse cardiac events (MACE) among elderly non-valvular AF (NVAF) Medicare patients prescribed direct oral anticoagulants (DOACs) vs warfarin. NVAF patients aged ≥ 65 years who initiated DOACs (apixaban, dabigatran, and rivaroxaban) or warfarin were selected from 01JAN2013-31DEC2015 in CMS Medicare data. Propensity score matching was used to balance DOAC and warfarin cohorts. Cox proportional hazards models estimated the risk of stroke/SE, MB, NCO, and MACE. 37,525 apixaban–warfarin, 18,131 dabigatran–warfarin, and 55,359 rivaroxaban–warfarin pairs were included. Compared to warfarin, apixaban (HR: 0.69; 95% CI 0.59–0.81) and rivaroxaban (HR: 0.82; 95% CI 0.73–0.91) had lower risk of stroke/SE, and dabigatran (HR: 0.88; 95% CI 0.72–1.07) had similar risk of stroke/SE. Apixaban (MB: HR: 0.61; 95% CI 0.57–0.67; NCO: HR: 0.64; 95% CI 0.60–0.69) and dabigatran (MB: HR: 0.79; 95% CI 0.71–0.89; NCO: HR: 0.84; 95% CI 0.76–0.93) had lower risk of MB and NCO, and rivaroxaban had higher risk of MB (HR: 1.08; 95% CI 1.02–1.14) and similar risk of NCO (HR: 1.04; 95% CI 0.99–1.09). Compared to warfarin, apixaban had a lower risk for stroke/SE, MB, and NCO; dabigatran had a lower risk of MB and NCO; and rivaroxaban had a lower risk of stroke/SE but higher risk of MB. All DOACs had lower risk of MACE compared to warfarin.

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P690Incidence of events between vitamin K antagonists and direct oral anticoagulants in patients with cancer

European Heart Journal ◽

10.1093/eurheartj/ehz747.0295 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

A Pardo Sanz ◽

L M Rincon ◽

G De Lara ◽

A Tamayo ◽

L C Belarte ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Systemic Embolism ◽

Bleeding Events ◽

Patients With Cancer

Abstract Background Balance between embolic and bleeding risk is challenging in patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We aimed to evaluate the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with breast cancer. We also compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. Methods It is an ambispective observational multicentric study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain in the period 2011–2018. A total of 1237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. The incidence of thromboembolic and major bleeding events according to the antithrombotic strategy with VKAs or DOACs was evaluated in the cohort of 637 patients with cancer. Analysis were conducted using SPSS software V.22.0 and R V.3.5.1, with a two-tailed significance value of 0.05. Results Mean follow-up was 3.1 years. Both groups were similar in age, CHA2DS2-VASc and HASB-LED scores. There was no evidence that the incidence of ischemic stroke/systemic embolism differed between patients with cancer treated with AVK and DOAC after CHA2DS2-VASc adjustment: HR 0.91 (95% CI, 0.42–1.99). In addition, no significant differences in the incidence of major bleeding events were found between DOACs and VKA after adjustment for HAS-BLED score: HR 1.53 (95% CI, 0.93–2.53) (Figure 3). Gastrointestinal bleeding was the main source of haemorrhages in both groups (45% of bleedings among patients treated with DOACs and, 37% in VKAs group). Metastatic disease or active chemotherapy were studied as potential covariates but none of them posed any relevant change in the result. Kaplan-Meier analysis Conclusions Cancer patients treated with DOACs did not differ versus those treated with VKAs with regards to stroke or systemic embolism in a model adjusted for CHA2DS2-VASc. Neither significant differences were found for bleeding events in a model adjusted for baseline HASBLED.

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