ICH in primary or metastatic brain cancer patients with or without anticoagulant treatment: a systematic review and meta-analysis

Abstract

Anticoagulant treatment in patients with primary and metastatic brain cancer is a concern due to risk of intracranial hemorrhage (ICH). We performed a systematic review and meta-analysis to evaluate the risk of ICH in patients with primary or metastatic brain cancer treated or not with anticoagulants. Articles on ICH in patients with primary or metastatic brain cancer treated or not with anticoagulants published up to September 2021 were identified by searching PUBMED, EMBASE and CENTRAL.The primary outcome of this analysis was ICH. Thirty studies were included. Rate of ICH was 13.0% in 1,009 patients with metastatic and 6.4% in 2,353 patients with primary brain cancer [Relative risk (RR) 3.26, 95% CI 2.69-3.94; I2 92.8%). In patients with primary brain cancer, ICH occurred in 12.5% and 4.4% of patients treated or not treated with anticoagulants, respectively [11 studies, 659 treated and 1,346 not treated patients, RR 2.63, 95% CI 1.48-4.67, I2 49.6%]. In patients with metastatic brain cancer, ICH occurred in 14.7% and 15.4%, respectively (5 studies, 265 treated and 301 not treated patients, RR 0.92, 95% CI 0.43-1.93, I2 0%). ICH occurred in 8.3% of 172 treated with direct oral anticoagulant (DOAC) and in 11.7% of 278 treated with low-molecular weight heparin (LMWH) (5 studies, RR 0.44, 95% CI 0.25-0.79, I2 0%). Patients with metastatic brain cancer have a particularly high risk of ICH. Patients with primary brain cancer have an increased risk of ICH during anticoagulation. DOACs are associated with a lower risk of ICH than LMWH.

Practical guidance for direct oral anticoagulant use in the treatment of venous thromboembolism in primary and metastatic brain tumor patients

“…Many studies find that anticoagulation for VTE in patients with GBM substantially increases the rate of ICH compared with patients with GBM with or without VTE, who did not receive anticoagulation. [16][17][18][19] Alternatively, other retrospective studies fail to show an increased risk of symptomatic ICH in LMWH-treated patients with glioma. 20,21 A retrospective matched cohort study of 220 patients with glioma found a cumulative 1-year risk of symptomatic ICH of 17% in patients receiving LMWH for VTE versus 13% for matched patients without VTE and no median survival difference.…”

“…A systematic review of 3893 patients found that ICH rates were much higher in BM compared with primary BTs (13% vs. 6.4%, respectively). 19 Some report ICH rates as much as 20% in metastatic cancer patients. 47 Counterintuitively, studies report no increase in ICH for metastatic patients with BT treated with LMWH versus no anticoagulation, to a 3-fold increase ICH risk in primary patients with BT receiving LMWH versus no anticoagulation.…”

“…47 Counterintuitively, studies report no increase in ICH for metastatic patients with BT treated with LMWH versus no anticoagulation, to a 3-fold increase ICH risk in primary patients with BT receiving LMWH versus no anticoagulation. 17,19,22,47 Several retrospective studies have examined the DOACs safety profile in the BT population. A retrospective cohort study with primary and metastatic patients with BT treated with DOACs and LMWH showed no increased incidence of ICH.…”

DOACs for VTE in patients with brain cancer and brain metastases: choices, choices, choices

“…Giustozzi et al 1 recently published a systematic review and meta-analysis that investigated intracranial hemorrhage (ICH) in patients with primary or metastatic brain cancer managed with or without anticoagulants. The analysis included 30 retrospective studies and concluded that (1) the rate of ICH and major ICH is higher in patients with metastatic brain cancer than in those with primary brain cancer (all ICH, 13% vs 6.4%; major ICH, 15.4% vs 3.9%), (2) anticoagulation is associated with an increased risk of ICH and major ICH in patients with primary brain cancer but not in those with metastatic brain cancer, and (3) the risk of ICH is a third lower in patients treated with a direct oral anticoagulant (DOAC) than in those treated with low-molecular-weight heparin (LMWH).…”

DOACs in patients with brain cancers: promising but still a long way to go

“…We wish to thank Buka and Sutton for their comments on our recently published article. 1 Among the results of our meta-analysis of patients with primary or metastatic brain cancer and VTE, the authors focused their attention on the lower risk of intracranial bleeding (ICH) in patients treated with direct oral anticoagulants (DOACs) than that in those receiving low-molecular weight heparin (LMWH) and advice caution for implementing this finding in the clinical practice. The authors state that these conclusions are driven mainly by Carney’s study, which has several limitations including (1) the retrospective design, (2) the patient population, and (3) the potential selection bias.…”