Extended Thromboprophylaxis Does Not Reduce VTE Incidence in Hospitalized Patients With Cancer

The use of extended thromboprophylaxis with enoxaparin, betrixaban, or rivaroxaban does not reduce the risk of venous thromboembolic (VTE) events in hospitalized patients with active cancer or a history of cancer, according to findings published in Blood Advances. However, it may increase the risk of bleeding in these patients.

Following hospitalization, patients with cancer remain at “higher risk of both bleeding and thrombosis due to underlying disease, therapies, or interventions,” corresponding study author, Jeffrey Zwicker, MD, of Harvard Medical School, told ASH Clinical News. Patients who develop VTE after hospital discharge despite the use of thromboprophylaxis tend to have a higher risk of death. Previous research suggested extended thromboprophylaxis may reduce VTE incidence in patients hospitalized for medical issues, but this benefit comes at the cost of an increased risk of hemorrhage.

“Based on these research data, which suggest that extended prophylaxis is associated with a stronger signal for increased hemorrhage relative to thrombosis reduction, I would not advocate for routine extended prophylaxis following hospitalization for patients with cancer,” Dr. Zwicker said of the current study.

Dr. Zwicker and colleagues performed a systematic review and meta-analysis of four randomized controlled trials that compared extended prophylaxis with enoxaparin, betrixaban, or rivaroxaban versus standard-duration prophylaxis with enoxaparin in patients with active cancer or a history of cancer who were hospitalized for medical issues (n=3,655). Approximately 80% of the pooled cohort had a history of cancer, while the remaining 20% had active cancer.

Patients received either:

  • extended-duration prophylaxis using enoxaparin, betrixaban, or rivaroxaban (n=1,832)
  • standard-duration prophylaxis using enoxaparin monotherapy (n=1,853)

The pooled analysis found no significant differences between the extended prophylaxis arm and the standard prophylaxis group in terms of the rate of VTE events (odds ratio [OR] = 0.85; 95% CI 0.61-1.18). Participants who received extended-duration thromboprophylaxis had a higher risk of clinically relevant bleeding (OR=2.11; 95% CI 1.33-3.35). There was no significant risk of major bleeding (OR=1.98; 95% CI 0.62-6.35) or clinically relevant nonmajor bleeding (OR=1.85; 95% CI 0.87-3.92).

In a pooled analysis of three studies, which excluded a study without patients with active cancer, the investigators found no differences in total VTEs between the groups (OR=0.86; 95% CI 0.61-1.20). However, extended thromboprophylaxis in this analysis was associated with a significant increase in clinically relevant bleeding (OR=2.21; 95% CI 1.02-4.80).

The use of extended thromboprophylaxis also was associated with significant reduction in the risk of VTE in patients without cancer (OR=0.72; 95% CI 0.61-0.84), but no similar association was found in those with cancer. There was a higher risk of clinically relevant bleeding in patients with and without cancer who received extended thromboprophylaxis.

This meta-analysis is limited by its inclusion of studies that only assessed apixaban, enoxaparin, and rivaroxaban, which the investigators suggest limits the generalizability of the findings to other direct oral anticoagulants.

Another limitation of this research is the studies’ varied definitions of cancer history. “Whether a more targeted approach based on individual assessment of bleeding versus thrombosis risk factors would alter the risk-benefit profile is not yet known,” Dr. Zwicker added.

The authors report no relevant conflicts of interest.


Osataphan S, Patell R, Chiasakul T, Khorana AA, Zwicker JI. Extended thromboprophylaxis for medically ill patients with cancer: a systemic review and meta-analysis. Blood Adv. 2021;5(8):2055-2062.