LAUSR

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). Here, we offer some further thoughts on the third conclusion. In the trials of DOACs versus LMWH for cancer-associated venous thromboembolism (VTE), there were very low numbers of patients with primary brain cancers: none in the Caravaggio trial 2 and 8 of 300 patients (2.7%) in the ADAM-VTE trial 3 (both apixaban), and 3 of 406 patients (0.7%) in SELECT-D 4 (rivaroxaban). Conversely, the Hokusai VTE cancer trial of edoxaban vs dalteparin included 74 patients with brain cancer or metastases. 5 In this group, there were major bleeding events in 2 of 31 patients (6.5%) treated with edoxaban vs 3 of 43 patients (7.0%) treated with dalteparin, which is a nonsigni fi cant difference, although the trial was not powered for the analysis of this subgroup. Therefore, we are also reliant on retrospective studies