Direct oral anticoagulants bleeding events in patients with atrial fibrillation vs. venous thromboembolism admitted to an emergency department: Real-life study

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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Evaluation of Direct Oral Anticoagulant Prescribing in Patients With Moderate to Severe Renal Impairment

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620987900 ◽

2021 ◽

Vol 27 ◽

pp. 107602962098790

Author(s):

Clara Ting ◽

Megan Rhoten ◽

Jillian Dempsey ◽

Hunter Nichols ◽

John Fanikos ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Impairment ◽

Severe Renal Impairment ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Events ◽

Increase Risk ◽

Severe Chronic Kidney Disease ◽

Dosing Strategies ◽

Require Dose

Patients with renal impairment require dose adjustments for direct oral anticoagulants (DOACs), though there is uncertainty regarding their use in severe chronic kidney disease. Inappropriately dosed DOACs may increase risk of ischemic events when under-dosed, or risk of bleeding when over-dosed. The purpose of this study was to describe DOAC selection, dosing strategies, and associated clinical outcomes in patients with moderate to severe renal impairment at our institution. This was a single-center retrospective analysis of adult outpatients with moderate to severe renal impairment (estimated creatinine clearance <50 mL/min, including need for hemodialysis) who were prescribed a DOAC by a cardiologist between June 1, 2015 and December 1, 2018. Outcomes evaluated included the percentage of patients who received appropriate and inappropriate DOAC dosing, prescriber reasons for inappropriate DOAC dosing if documented, and incidence of thrombotic and bleeding events. A total of 207 patients were included. Overall, 61 (29.5%) patients received inappropriate dosing, with 43 (70.5%) being under-dosed and 18 (29.5%) being over-dosed as compared to FDA-labeled dosing recommendations for atrial fibrillation or venous thromboembolism (VTE). By a median follow-up duration of 20 months, stroke occurred in 6 (3.3%) patients receiving DOACs for atrial fibrillation, and VTE occurred in 1 (4.3%) patient receiving a DOAC for VTE. International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding occurred in 25 (12.1%) patients. Direct oral anticoagulants were frequently prescribed at off-label doses in patients with moderate to severe renal impairment, with a tendency toward under-dosing.

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Direct oral anticoagulants in the early phase of non valvular atrial fibrillation-related acute ischemic stroke: focus on real life studies

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-018-1775-2 ◽

2018 ◽

Vol 47 (2) ◽

pp. 292-300 ◽

Cited By ~ 3

Author(s):

Luca Masotti ◽

Elisa Grifoni ◽

Alessandro Dei ◽

Vieri Vannucchi ◽

Federico Moroni ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Early Phase ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Real Life

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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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Anticoagulation Challenges in Hematogeriatrics: Effectiveness and Safety of Direct Oral Anticoagulants Vs Vitamin k Antagonist in Elderly with Atrial Fibrillation

Blood ◽

10.1182/blood-2019-125150 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1162-1162

Author(s):

Desirée Campoy ◽

Gonzalo Artaza ◽

César A Velasquez ◽

Tania Canals ◽

Erik A Johansson ◽

...

Keyword(s):

Atrial Fibrillation ◽

Elderly Patients ◽

Vitamin K ◽

Major Bleeding ◽

Frail Elderly ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Systemic Embolism ◽

Bleeding Events

BACKGROUND Direct oral anticoagulants (DOAC) are increasingly used in patients with Non Valvular Atrial Fibrillation (NVAF) for stroke prevention. However, Follow-Up (FU) and dosing these agents in the elderly can be challenging due to different factors, such as chronic kidney disease, frailty, falls, multifactorial anemia and concomitant polypharmacy. These factors in elderly patients predisposes to both thromboembolic and bleeding events once atrial fibrillation occurs. Therefore, balancing risks and benefits of antithrombotic strategies in older populations is crucial. Despite recent increases in DOAC use in NVAF, there are still limited data regarding DOACs effectiveness and safety in frail elderly patients. AIM To assess the effectiveness and safety according to DOAC or Vitamin K Antagonist (VKA) in a cohort of elderly patients with NVAF. METHODS From April 2016 to April 2019, we consecutively included NVAF elderly patients (≥80 years-old) treated with DOAC or VKA in a prospective multicenter registry. Demographic, laboratory, frailty risk stratification and antithrombotic therapy data were collected. Patients had a minimum FU of 6 months. VKA patients had a standard FU through digital international normalized ratio (INR) control and the efficacy of therapy was determined by the time in therapeutic range (TTR) values from the preceding 6 months of treatment using Rosendaal's method. FU in DOAC patients was performed through structured and integral assessment following the Tromboc@t Working Group recommendations for management in patients receiving DOAC (Olivera et al, Med Clin 2018). Key practical management aspects are listed in the flow chart (Figure 1). Clinical Frailty Scale (CFS score) was assigned to each patient at the beginning and during the FU; patients were classified into three categories: non-frail (CFS 1-4), mild-to-moderately frail (CFS 5-6), and severely frail (CFS 7-9). RESULTS From a total of 1040 NVAF patients, 690 (63.5%) were treated with DOAC (61 dabigatran, 95 rivaroxaban, 254 edoxaban and 280 apixaban) and 350 with VKA. In the VKA group, the mean TTR was 52.8%. Demographic characteristics and CFS score are summarized in table 1. Kaplan-Meier analysis (median FU: 16.5 months) showed a significantly high incidence of stroke/systemic embolism among VKA patients vs DOAC patients (4.2 vs 0.5 events per 100 patient-years, p<0.001). Major bleeding in the DOAC group was significantly infrequent compared with VKA group (2.2 vs 8.9 events, p=0.001). In the DOAC group, 90% (n=20/22) of the major bleedings were gastrointestinal [16 rivaroxaban and 4 edoxaban]. However, in the VKA group 64% (n = 20/31) were gastrointestinal, 25.8% (n= 8/31) intracranial and 9.7% (n = 3/31) urogenital bleedings. We identified 365 very elderly patients (aged ≥ 90 years) of which 270 (39.1%) were DOAC patients and 95 (27.1%) VKA patients. In this subgroup of patients, after a multivariate regression analysis, the stroke/systemic embolism incidence was similar in both treatment groups regardless of the age, but major bleeding decreased significantly in DOAC group (adjusted HR 0.247, 95% CI 0.091-0.664). CONCLUSIONS Our data indicate that DOACs can be a good therapeutic option for stroke/systemic embolism prevention in frail elderly patients, showing low rates of stroke as well as bleeding events when a structured and integral FU is applied to anticoagulated patients. Further investigations are necessary to analyze the impact in the quality of life and net clinical benefit of anticoagulant therapy when a FU program is applied in elderly patients. Disclosures Sierra: Novartis: Honoraria, Research Funding, Speakers Bureau; Astellas: Honoraria; Pfizer: Honoraria; Daiichi-Sankyo: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Roche: Honoraria; Jazz Pharmaceuticals: Honoraria.

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Safety and timing of resuming dabigatran after major gastrointestinal bleeding reversed by idarucizumab

SAGE Open Medical Case Reports ◽

10.1177/2050313x17753336 ◽

2018 ◽

Vol 6 ◽

pp. 2050313X1775333 ◽

Cited By ~ 1

Author(s):

Gian Galeazzo Riario Sforza ◽

Francesco Gentile ◽

Fabio Stock ◽

Francesco Caggiano ◽

Enrica Chiocca ◽

...

Keyword(s):

Atrial Fibrillation ◽

Case Report ◽

Major Bleeding ◽

Acute Treatment ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Oral Vitamin ◽

Bleeding Events ◽

Massive Rectal Bleeding

The recent introduction of direct oral anticoagulants, including rivaroxaban, dabigatran, apixaban, and edoxaban, for the acute treatment and secondary prevention of venous thromboembolism and in atrial fibrillation has been shown to provide greater clinical benefit than oral vitamin K antagonists. However, direct oral anticoagulants are associated with adverse events, the most common being major bleeding; such events require the reversal of the anticoagulant effects by specific agents. In this case report, we describe an 87-year-old female with atrial fibrillation treated with dabigatran who had massive rectal bleeding. Idarucizumab 5 g (2 × 2.5 g/50 mL) was successfully used to reverse dabigatran effect; subsequent to this, treatment with dabigatran was resumed, and there were no further bleeding events. This suggests that dabigatran can be safely restarted after major bleeding, but this outcome needs to be confirmed in studies involving larger groups of patients.

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