Overall survival with warfarin vs. low-molecular-weight heparin in cancer-associated thrombosis

J Thromb Haemost. 2021 Nov;19(11):2825-2834. doi: 10.1111/jth.15519. Epub 2021 Sep 21.


Background: When compared with warfarin, low-molecular-weight heparin (LMWH) reduces the incidence of recurrent venous thromboembolism (VTE) in cancer. However, a survival benefit of LMWH over warfarin for the treatment of cancer-associated VTE has not been established.

Methods: Using the Surveillance, Epidemiology and End Results and Medicare linked database from 2007 through 2016, we identified Medicare beneficiaries (aged ≥66 years) who were: (1) diagnosed with primary gastric, colorectal, pancreatic, lung, ovarian, or brain cancer; (2) diagnosed with cancer-associated VTE; and (3) prescribed LMWH or warfarin within 30 days. The primary outcome was overall survival (OS). Patients were matched 1:1 using exact matching for cancer stage and propensity score matching for cancer diagnosis, age, year of VTE, and time from cancer diagnosis to index VTE. Cox proportional-hazards regression was performed to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).

Results: A total of 9706 patients were included. Warfarin was associated with a significant improvement in OS compared with LMWH (median OS, 9.8 months [95% CI, 9.1-10.4] vs. 7.2 months [95% CI, 6.8-7.8]; HR, 0.86; 95% CI 0.83-0.90; p < .001). The survival advantage was most pronounced in pancreatic (HR 0.82 [95% CI, 0.74-0.90], p < .001) and gastric cancers (HR 0.82 [95% CI, 0.68-0.98], p = .03). The observed differences in survival were consistent across subgroups including cancer stage, age, comorbidity burden, and year of VTE.

Conclusions: In this population-based study, warfarin was associated with improved OS compared with LMWH for the treatment of cancer-associated VTE.

Keywords: anticoagulation; cancer-associated thrombosis; low-molecular-weight heparin; venous thromboembolism; warfarin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Anticoagulants / adverse effects
  • Heparin
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Medicare
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Neoplasms* / epidemiology
  • Thrombosis*
  • United States / epidemiology
  • Venous Thromboembolism* / diagnosis
  • Venous Thromboembolism* / drug therapy
  • Venous Thromboembolism* / epidemiology
  • Warfarin / adverse effects


  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Warfarin
  • Heparin