Dataset Information

Intracranial hemorrhage with direct oral anticoagulants in patients with brain metastases.

ABSTRACT: Direct oral anticoagulants (DOACs) are increasingly prescribed in treatment of cancer-associated thrombosis, but limited data exist regarding safety of DOACs in patients with brain metastases. We aimed to determine the incidence of intracranial hemorrhage (ICH) in patients with brain metastases receiving DOACs or low-molecular-weight heparin (LMWH) for venous thromboembolism or atrial fibrillation. An international 2-center retrospective cohort study was designed. Follow-up started on the first day of concomitant anticoagulation and brain tumor diagnosis. At least 2 brain imaging studies were mandated. The primary outcome was the cumulative incidence of any spontaneous ICH at 12-month follow-up with death as a competing risk. Major ICH was defined as spontaneous, ?10 mL in volume, symptomatic, or requiring surgical intervention. Imaging studies were centrally reviewed by a neuroradiologist blinded for anticoagulant type. PANWARDS (platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, stroke) score for prediction of ICH was calculated. We included 96 patients with brain metastases (41 DOAC, 55 LMWH). The 12-month cumulative incidence of major ICH was 5.1% in DOAC-treated patients and 11.1% in those treated with LMWH (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.09-2.21). When anticoagulation was analyzed as a time-varying covariate, the risk of any ICH did not differ between DOAC- and LMWH-treated patients (HR, 0.98; 95% CI, 0.28-3.40). PANWARDS score was not associated with ICH risk. This international 2-center study suggests comparable safety of LMWH and DOACs in patients with brain metastases.

SUBMITTER: Leader A

PROVIDER: S-EPMC7756985 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Intracranial hemorrhage with direct oral anticoagulants in patients with brain metastases.

Leader Avi A Hamulyák Eva N EN Carney Brian J BJ Avrahami Maya M Knip Jelijn J JJ Rozenblatt Shira S Beenen Ludo F M LFM Yust-Katz Shlomit S Icht Oded O Coppens Michiel M Raanani Pia P Middeldorp Saskia S Büller Harry R HR Zwicker Jeffrey I JI Spectre Galia G

Blood advances 20201201 24

Direct oral anticoagulants (DOACs) are increasingly prescribed in treatment of cancer-associated thrombosis, but limited data exist regarding safety of DOACs in patients with brain metastases. We aimed to determine the incidence of intracranial hemorrhage (ICH) in patients with brain metastases receiving DOACs or low-molecular-weight heparin (LMWH) for venous thromboembolism or atrial fibrillation. An international 2-center retrospective cohort study was designed. Follow-up started on the first ...[more]

PMID: 33351124

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Project description:ImportanceTamoxifen is commonly used as adjuvant therapy in breast cancer and is proposed to interfere with cytochrome P450 enzyme and P-glycoprotein pathways. Concurrent use with direct oral anticoagulants (DOACs) poses the threat of a potentially dangerous drug-drug interaction by leading to an increase in hemorrhage risk.ObjectiveTo assess the risk of hemorrhage in patients with breast cancer coprescribed a DOAC and tamoxifen compared with a DOAC and an aromatase inhibitor (AI).Design, setting, and participantsThis population-based, retrospective cohort study was conducted among adults aged 66 years or older who were prescribed tamoxifen (compared with an AI) concurrently with a DOAC in Ontario, Canada, between June 23, 2009, and November 30, 2020, and followed up until December 31, 2020.InterventionsConcurrent prescription of a DOAC and tamoxifen compared with a DOAC and an AI.Main outcomes and measuresThe primary outcome was major hemorrhage requiring an emergency department visit or hospitalization after prescription. Overlap weighted Cox proportional hazards models, accounting for multiple covariates, were used to assess the association between hemorrhage and tamoxifen or AI use with a DOAC.ResultsAmong a total of 4753 patients (4679 [98.4%] women; mean [SD] age, 77.4 [7.4] years), 1179 (24.8%) were prescribed tamoxifen, and 3574 (75.2%) were prescribed an AI. Rivaroxaban (2530 [53.2%]) and apixaban (1665 [35.0%]) were the most frequently used DOACs. Patients taking AIs were younger than patients taking tamoxifen (mean [SD] age, 77.1 [7.3] vs 78.3 [7.6] years), with higher Charlson Comorbidity Index (mean [SD], 1.8 [2.4] vs 1.5 [2.2]) and more advanced cancer stage (stages III and IV, 569 [15.9%] vs 127 [10.8%]). During a median follow-up of 166 days (IQR, 111-527 days), tamoxifen was not associated with a higher risk of major hemorrhage (29 of 1179 [2.5%]) compared with an AI (119 of 3574 [3.3%]) when combined with a DOAC (absolute risk difference, -0.8%; weighted hazard ratio, 0.68 [95% CI, 0.44-1.06]). These results were similar in additional analyses using a more liberal definition of hemorrhage, accounting for kidney function, limiting follow-up to 90 days, stratifying by incident and prevalent DOAC users, and accounting for cancer duration and the competing risk of death.Conclusions and relevanceIn this cohort study, findings suggest that among DOAC users, the concurrent use of tamoxifen was not associated with a higher risk of hemorrhage compared with the concurrent use of an AI. These findings should directly inform prescribers regarding the apparent safety of concurrent DOAC and tamoxifen use.

Project description:BackgroundOver the past 5 years, dabigatran, rivaroxaban and apixaban were approved for stroke prevention. Phase III studies have shown a lower risk of intracranial bleeding with these direct oral anticoagulants than with warfarin; however, there is a lack of real-life data to validate this. We analyzed time trends in atraumatic intracranial bleeding from 2009 to 2013 among patients prescribed oral anticoagulants and those not prescribed oral anticoagulants.MethodsWe used ICD-10-CA (enhanced Canadian version of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) codes to identify all patients with atraumatic intracranial bleeding who presented to our neurosurgical centre (serving a population of more than 1.2 million). Trained researchers extracted data on anticoagulant medications used in the week before diagnosis of the intracranial bleed. Provincial prescription data for oral anticoagulants were obtained from IMS Brogan CompuScript Market Dynamics. The primary outcome was the time trend in incident intracranial bleeds associated with oral anticoagulation during the period 2009-2013. The secondary outcomes were the time trend in intracranial bleeds not associated with oral anticoagulation and the provincial prescribing patterns for oral anticoagulants during the same period.ResultsA total of 2050 patients presented with atraumatic intracranial bleeds during the study period. Of the 371 (18%) prescribed an anticoagulant in the week before presentation, 335 were prescribed an oral anticoagulant. There was an increasing time trend in intracranial bleeding associated with oral anticoagulants (p = 0.009; 6 additional events per year) and in intracranial bleeding not associated with oral anticoagulation (p = 0.06). During 2013, prescriptions for warfarin decreased to 70% of all oral anticoagulant prescriptions in the province, whereas those for dabigatran and rivaroxaban increased to 17% and 12%, respectively.InterpretationWe observed increasing time trends in intracranial bleeding, both associated with and not associated with oral anticoagulants, over the study period. Although aggregate provincial data showed increased prescribing of oral anticoagulants, other more likely explanations for our findings include an aging population or increasing frailty.

Project description:Background and purposeThe use of direct oral anticoagulants (DOAC) has increased sharply and DOAC are the oral anticoagulant therapy (OAT) of choice for the majority of patients with newly-diagnosed atrial fibrillation. Intracranial hemorrhage is the most severe adverse event of OAT. Systematic data on the course of intracranial hemorrhage under DOAC compared to vitamin K antagonists (VKA) are warranted to enable shared decision making in AF patients needing OAT.MethodsThis is a secondary analysis of the patients with intracranial bleedings from the prospective multicenter emergency department-based RADOA registry, which collected data on patients admitted with major bleeding while taking VKA or DOAC. The primary endpoint was in-hospital mortality until day 30. We evaluated hematoma volume and short-term clinical outcomes in relation to the extent of active OAT according to coagulation parameters and OAT plasma levels measured by UPLC-MS/MS.ResultsOf 193 patients with major bleeding, 109 (56.5%) had intracranial hemorrhage [52.3% intracerebral (ICH), 33.9% subdural (SDH), 11.0% subarachnoidal (SAH)]. 64 (58.7%) were on VKA and 45 (41.2%) were on DOAC. On admission, we could confirm active anticoagulation in 97.7% of VKA-treated patients based on either INR > 1.3 or phenprocoumon levels and in 75.8% of DOAC-treated patients based on DOAC levels. Patients suffering an intracranial hemorrhage under VKA showed significantly larger hematoma volumes and a higher in-hospital mortality. Especially in intracerebral hemorrhage, we observed a higher initial severity and numerically greater proportion of early changes towards palliative therapy under VKA, which coincided with a numerically higher case fatality.ConclusionsWe show significantly smaller hematoma volumes for ICH and SDH under DOAC in comparison to VKA and a significantly lower 30-day in-hospital mortality rate of DOAC-ICH, even before the introduction of specific antidotes. These data strongly support the use of DOAC whenever possible in patients requiring OAT.Trial registrationhttp://www.Clinicaltrialsgov ; Unique identifier: NCT01722786.

Dataset Information

Intracranial hemorrhage with direct oral anticoagulants in patients with brain metastases.

Publications

Intracranial hemorrhage with direct oral anticoagulants in patients with brain metastases.

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