Intracranial hemorrhage with direct oral anticoagulants in patients with brain metastases

Leader, Avi; Hamulyák, Eva N.; Carney, Brian J.; Avrahami, Maya; Knip, Jelijn J.; Rozenblatt, Shira; Beenen, Ludo F. M.; Yust‐Katz, Shlomit; Icht, Oded; Coppens, Michiel; Raanani, Pia; Büller, Harry R.; Zwicker, Jeffrey I.; Spectre, Galia

doi:10.1182/bloodadvances.2020003238

Cited by 32 publications

(21 citation statements)

References 26 publications

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“…The incidence of any ICH among patients with brain tumors is high but does not appear to be influenced by the administration of anticoagulants. 4,[7][8][9]24,25 Similar data on the safety of aspirin in patients with brain metastases is lacking. In this matched cohort study of nearly 400 patients with blinded radiology review of ICH, the administration of antiplatelet therapy was not associated with an increase in the incidence, size, or severity of ICH in the setting of brain metastases.…”

Section: Discussionmentioning

confidence: 99%

Antiplatelet medications and risk of intracranial hemorrhage in patients with metastatic brain tumors

Miller¹,

Patell

Uhlmann

et al. 2022

Blood Advances

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Although intracranial hemorrhage (ICH) is frequent in the setting of brain metastases, there are limited data on the influence of antiplatelet agents on the development of brain-tumor associated ICH. To evaluate whether the administration of anti-platelet agents increases the risk of ICH, we performed a matched cohort analysis of patients with metastatic brain tumors with blinded radiology review. Study population included 392 patients with metastatic brain tumors (134 received antiplatelet agents and 258 controls). Non-small cell lung cancer was the most common malignancy in the cohort (74.0%), followed by small cell lung cancer (9.9%), melanoma (4.6%), and renal cell cancer (4.3%). Among those who received an antiplatelet agent, 86.6% received aspirin alone and 23.1% received therapeutic anticoagulation during the study period. The cumulative incidence of any ICH at one year was 19.3% (95% CI, 14.1-24.4%) in patients not receiving anti-platelet agents compared to 22.5% (95% CI, 15.2-29.8%, Gray test P=0.22) in those receiving anti-platelet agents. Cumulative incidence of major ICH was 5.4% (95% CI, 2.6-8.3%) among controls compared with 5.5% (95% CI, 1.5-9.5%, P=0.80) in those exposed to antiplatelet agents. The combination of anticoagulation with antiplatelet agents did not increase the risk of major ICH. The use of antiplatelet agents was not associated with an increase in the incidence, size, or severity of ICH in the setting of brain metastases.

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Section: Discussionmentioning

confidence: 99%

Antiplatelet medications and risk of intracranial hemorrhage in patients with metastatic brain tumors

Miller¹,

Patell

Uhlmann

et al. 2022

Blood Advances

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“…Similarly, an international two-center study suggested comparable safety of LMWH and DOACs in patients with brain metastases. The 12-month cumulative incidence of major ICH was 5.1% in DOAC-treated patients and 11.1% in those treated with LMWH (HR: 0.45; 95% CI 0.09 to 2.21) [ 46 ]. 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 to 3.40) [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…The 12-month cumulative incidence of major ICH was 5.1% in DOAC-treated patients and 11.1% in those treated with LMWH (HR: 0.45; 95% CI 0.09 to 2.21) [ 46 ]. 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 to 3.40) [ 46 ]. Finally, a single-center retrospective chart review of 125 patients with primary and metastatic brain tumors on anticoagulation reported rates of major bleeding of 26% and 9.6% in patients receiving LMWH or DOAC, respectively [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Treatment Algorithm in Cancer-Associated Thrombosis: Updated Canadian Expert Consensus

et al. 2021

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Patients with cancer-associated thrombosis (CAT) are at high risk of recurrent venous thromboembolism (VTE) and major bleeding complications. Risks vary significantly between individuals based on cancer status, treatment, and other characteristics. To facilitate the evidence-based management of anticoagulant therapy in this patient population, a committee of 11 Canadian clinical experts updated a consensus-based algorithm for the acute and extended treatment of symptomatic and incidental CAT that was developed in 2018. Following a systematic review of the literature, updates to the algorithm were discussed during an online teleconference, and the algorithm was subsequently refined based on feedback from committee members. Clinicians using this treatment algorithm should consider bleeding risk, type of cancer, and drug–drug interactions, as well as patient and clinician preferences, in tailoring anticoagulation for patients with CAT. Anticoagulant therapy should be adapted as the patient’s cancer status and management change over time.

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“…In a meta-analysis of studies evaluating the risk of ICH in patients with brain metastases receiving anticoagulation, therapeutic doses of LMWH did not increase the risk of ICH compared with no anticoagulation (OR 1.07, 95% CI 0.61-1.88) [35]. Finally, a retrospective cohort of patients with brain metastases receiving anticoagulation found that the cumulative incidence of ICH at 12 months did not differ between patients treated with DOAC and those treated with LMWH (5.1% vs.11.1%, HR 0.45, 95% CI 0.09-2.21) [36].…”

Section: Cancer Site and Stagementioning

confidence: 97%

Incidence, risk factors, and management of bleeding in patients receiving anticoagulants for the treatment of cancer-associated thrombosis

Frère

Font

Espósito

et al. 2021

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Updated clinical practice guidelines recommend the long-term use of low-molecular-weight heparins or direct oral anticoagulants as the preferred option for the treatment of cancer-associated thrombosis (CAT), using a personalized approach matching the right drug to the right patient. In most cases, the benefit of anticoagulant therapy outweighs the risk. However, the long-term use of anticoagulants is associated with a non-negligible risk of bleeding, which constitutes a rare but serious adverse effect. Bleeding complications have been reported to be overall 2 to 3 times more frequent in cancer patients with CAT receiving anticoagulation than in non-cancer patients, with a reported incidence of major bleeding ranging from 2.4 to 16.0% in randomized controlled trials (RCT). In the absence of validated risk assessment model to predict the risk of bleeding in these patients, a careful evaluation of each individual profile, with adequate selection of the most appropriate anticoagulant for each individual patient, is warranted for overcoming management challenges, taking in account the numerous factors which may potentiate the overall bleeding risk in these complex patients, such as advanced or metastatic disease, older age, anemia, thrombocytopenia, renal impairment, liver dysfunction, and concomitant anticancer therapies. The purpose of this review is to call for awareness on bleeding complications as a major safety issue of CAT treatment and to summarize data from recent RCT and real-world studies on the incidence and risk factors for bleeding in this unique and challenging population to further help clinicians in decision-making. KeywordsCancer-associated thrombosis • Anticoagulants • Direct oral anticoagulants • Low-molecular-weight heparin • Bleeding * Nicolas Janus

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Intracranial hemorrhage with direct oral anticoagulants in patients with brain metastases

Cited by 32 publications

References 26 publications

Antiplatelet medications and risk of intracranial hemorrhage in patients with metastatic brain tumors

Antiplatelet medications and risk of intracranial hemorrhage in patients with metastatic brain tumors

Treatment Algorithm in Cancer-Associated Thrombosis: Updated Canadian Expert Consensus

Incidence, risk factors, and management of bleeding in patients receiving anticoagulants for the treatment of cancer-associated thrombosis

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