Direct oral anticoagulants versus low-molecular-weight heparin in Asian patients with cancer-associated venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly used as an alternative to low-molecular-weight heparin (LMWH) for cancer-associated venous thromboembolism (VTE), but evidence in Asian patients remains limited. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for randomized or comparative observational studies comparing DOACs with LMWH for cancer-associated VTE in Asian patients. Primary outcomes were recurrent VTE and major bleeding. Weighted hazard ratios (wHR) were pooled as the primary analysis; subdistribution hazard ratios (sHRs) from competing-risk models were pooled as a sensitivity analysis. RESULTS: Seven observational studies comprising 13,387 patients were included; one early-terminated randomized trial was included in sensitivity analyses. In the primary analysis, DOACs were associated with lower recurrent VTE than LMWH (wHR 0.71, 95% CI 0.54-0.93), with similar major bleeding (wHR 0.85, 95% CI 0.70-1.04). All-cause mortality was lower with DOAC (wHR 0.66, 95% CI 0.60-0.71). After accounting for competing mortality, associations were attenuated for recurrent VTE (sHR 0.95, 95% CI 0.67-1.33) and shifted upward for major bleeding (sHR 1.09, 95% CI 0.95-1.26). In subgroup analyses, major bleeding was higher with a DOAC switching strategy (sHR 1.19, 95% CI 1.01-1.41); and in an exploratory competing-risk analysis, gastrointestinal bleeding was higher among patients with gastrointestinal cancer (p for subgroup difference = 0.041). CONCLUSIONS: In Asian patients with cancer-associated VTE, DOACs showed favorable associations in weighted analyses, but these were attenuated after accounting for competing mortality. Given the observational nature of the available evidence and marked mortality imbalance between treatment groups, these findings should be considered hypothesis-generating.