# Comparing survival with vitamin K antagonists, low-molecular-weight heparin, and direct oral anticoagulants in patients with cancer—a systematic review and meta-analysis

## TL;DR

This study compares survival rates of cancer patients using vitamin K antagonists versus newer anticoagulants, finding lower mortality with vitamin K antagonists in observational studies but not in randomized trials.

## Contribution

The study provides new insights into the survival benefits of vitamin K antagonists in cancer patients with venous thromboembolism compared to newer anticoagulants.

## Key findings

- Vitamin K antagonists were associated with lower mortality in observational studies compared to non-VKA anticoagulants.
- The survival benefit was most evident in patients with solid tumors and longer follow-up periods.
- Bleeding risk was similar across all anticoagulant types.

## Abstract

Venous thromboembolism (VTE) is a frequent complication in malignancy. Low-molecular-weight heparins and direct oral anticoagulants have replaced vitamin K antagonists (VKAs) as the standard of care for cancer-associated VTE. Nonetheless, clinical trials have not established a survival benefit of these agents compared with VKA.

We conducted a systematic review and meta-analysis to compare survival in cancer patients receiving VKA vs other anticoagulants.

We searched Embase, Web of Science, PubMed, ClinicalTrials.gov, and Cochrane from inception until April 10, 2025, focusing on the use of VKA and non-VKA in cancer patients. Primary outcome was mortality and secondary outcomes included thromboembolism and bleeding.

Of 11,198 studies screened, 14 studies (70,025 patients) were included. VKA were associated with lower mortality than non-VKA in observational studies (odds ratio [OR], 0.84; 95% CI, 0.78-0.91; I2 = 81%; n = 6 studies) but not in randomized controlled trials (OR, 0.99; 95% CI, 0.86-1.13; I2 = 0%; n = 8 studies). In subgroup analysis, follow-up period of >6 months (OR, 0.85; 95% CI, 0.79-0.92; I2 = 75%), solid malignancies (OR, 0.81; 95% CI, 0.75-0.88; I2 = 78%), and indication of VTE only (OR, 0.89; 95% CI, 0.83-0.96; I2 = 42%) demonstrated improved survival with VKA.

The use of VKA was associated with lower mortality than non-VKA anticoagulation in patients with cancer in observational studies but not in randomized trials. The analysis was limited by high heterogeneity, which must be considered when interpreting results.

•Venous thromboembolism is a frequent complication of malignancy, and although low-molecular-weight heparin and direct oral anticoagulants have replaced vitamin K antagonists as standard therapy, their effect on overall survival remains uncertain.•We conducted a systematic review and random-effects meta-analysis comparing vitamin K antagonists with low-molecular-weight heparin and direct oral anticoagulants in patients with cancer, with all-cause mortality as the primary outcome.•Vitamin K antagonist use was associated with lower mortality in observational studies but not in randomized controlled trials, with substantial statistical heterogeneity across studies.•The survival signal was most evident with longer follow-up, in solid tumors, and when anticoagulation was indicated for venous thromboembolism alone; however, heterogeneity limits causal inference and bleeding risk was similar across treatments.

Venous thromboembolism is a frequent complication of malignancy, and although low-molecular-weight heparin and direct oral anticoagulants have replaced vitamin K antagonists as standard therapy, their effect on overall survival remains uncertain.

We conducted a systematic review and random-effects meta-analysis comparing vitamin K antagonists with low-molecular-weight heparin and direct oral anticoagulants in patients with cancer, with all-cause mortality as the primary outcome.

Vitamin K antagonist use was associated with lower mortality in observational studies but not in randomized controlled trials, with substantial statistical heterogeneity across studies.

The survival signal was most evident with longer follow-up, in solid tumors, and when anticoagulation was indicated for venous thromboembolism alone; however, heterogeneity limits causal inference and bleeding risk was similar across treatments.