What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Cancer-associated thrombosis (n=49824). Intervention: Direct oral anticoagulants vs. Low-molecular-weight heparin. Primary outcome: Recurrent venous thromboembolism (RCTs) (RR 0.66, 95% CI 0.49-0.87).

What question did this study set out to answer?

This research compares the safety and effectiveness of direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) in cancer-associated thrombosis patients.

June 16, 2026Drug Safety0 citationsOpen Access

Safety and Effectiveness of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin for Cancer-Associated Thrombosis: A Systematic Review and Meta-analysis

WKWei KangTianjin University of Finance and Economics BLBowie P. Y. LamUniversity of Hong Kong RLRinko Tsz Lam LauWestern University

Key Result

In patients with cancer-associated thrombosis, direct oral anticoagulants significantly reduced the risk of recurrent venous thromboembolism compared to low-molecular-weight heparin (RR 0.66 in randomized controlled trials).

Key Points

This research compares the safety and effectiveness of direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) in cancer-associated thrombosis patients.
Systematic search of PubMed, Embase, and Cochrane Library databases until June 30, 2025.
Inclusion of seven randomized controlled trials and 28 cohort studies in the systematic review.
Meta-analysis of five randomized trials and 16 cohort studies, 49,824 patients analyzed with a fixed follow-up period of six months.
DOACs reduce recurrent venous thromboembolism compared to LMWH (RR 0.66; 95% CI 0.49-0.87).
No significant difference in all-cause mortality between DOACs and LMWH (RR 1.00; 95% CI 0.86-1.18).
Cohort studies show DOACs have a lower risk of all-cause mortality (RR 0.47; 95% CI 0.31-0.72).

Study Design

Type

Meta-Analysis (n=49,824)

Structured PICO

Do direct oral anticoagulants (DOACs) reduce recurrent venous thromboembolism and all-cause mortality without increasing major bleeding in patients with cancer-associated thrombosis compared to low-molecular-weight heparin?

Population

49,824 patients with cancer-associated thrombosis from 5 randomized controlled trials and 16 cohort studies, followed for 6 months to compare direct oral anticoagulants versus low-molecular-weight heparin.

Intervention

Direct oral anticoagulants (DOACs) as a class (including apixaban, edoxaban, rivaroxaban, dabigatran)

Comparator

Low-molecular-weight heparin (LMWH) (including dalteparin, enoxaparin, nadroparin)

Outcome

Recurrent venous thromboembolism, major bleeding, and all-cause mortality over a 6-month follow-up periodhard clinical

In patients with cancer-associated thrombosis, DOACs significantly reduce recurrent VTE and all-cause mortality compared to LMWH at 6 months, with comparable overall major bleeding risk.

Main Result

Relative Risk: 0.66 (95% CI 0.49–0.87)

Absolute Event Rate: 5.2% vs 8.2%

Limitations

RCTs referenced in the guidelines may have been underpowered to detect certain clinical outcomes such as bleeding events
Observational cohort studies are inherently more prone to methodological bias, residual confounding, and selection bias
Potential for immortal time bias in observational studies

Abstract

BACKGROUND: Cancer-associated thrombosis is a condition associated with high mortality rates, yet limited evidence exists regarding the safety and effectiveness of low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs), focusing on a fixed follow-up period based on clinical practice guideline recommendations. OBJECTIVE: This study aimed to compare the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated thrombosis over a 6-month follow-up period. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched up to 30 June, 2025. Recurrent venous thromboembolism, major bleeding, and all-cause mortality were pooled using a random-effects meta-analysis. RESULTS: Seven randomized controlled trials and 28 cohort studies were included in our systematic review. After applying the criteria for a 6-month follow-up period, five randomized controlled trials and 16 cohort studies with 49,824 patients were analyzed in the meta-analysis. In randomized controlled trials, DOACs showed a lower incidence of venous thromboembolism recurrence (relative risk RR 0.66, 95% confidence interval CI 0.49-0.87) compared with LMWH, with a non-significant increase in major bleeding (RR 1.28, 95% CI 0.87-1.88) and no significant difference in all-cause mortality (RR 1.00, 95% CI 0.86-1.18). Cohort studies demonstrated a lower incidence of venous thromboembolism recurrence (RR 0.69, 95% CI 0.62-0.76) with DOACs, a non-significant reduction in major bleeding (RR 0.85, 95% CI 0.68-1.07), and a lower risk of all-cause mortality (RR 0.47, 95% CI 0.31-0.72). CONCLUSIONS: In patients with cancer-associated thrombosis, DOACs demonstrated a decrease in recurrent venous thromboembolism without increasing the risk of all-cause mortality. A non-significant increase in the risk of major bleeding was recorded in randomized controlled trials, but not in cohort studies. DOACs may provide greater effectiveness for cancer-associated thrombosis compared with LMWH.

Ask AI

Helpful

Bookmark

View Full Paper