Skip to content
evident
Original paper
2020NEJMHematology/Oncology

Caravaggio

Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer

RCTCancer-associated VTE

On this page

Overview

Oral apixaban was noninferior to dalteparin for recurrent cancer-associated VTE and did not increase major bleeding.

Clinical takeaway

Apixaban is an oral alternative to dalteparin for cancer-associated VTE. The result is noninferiority, not fewer recurrences. Major bleeding was not higher.

Key result

Recurrent VTE occurred in 32 of 576 patients (5.6%) on apixaban versus 46 of 579 (7.9%) on dalteparin (HR 0.63; 95% CI 0.37-1.07; P<0.001 for noninferiority).

Practice impact

Apixaban is a reasonable oral substitute for dalteparin in cancer-associated VTE when you need noninferiority without more major bleeding.

Evidence

Study design

Multinational, investigator-initiated, open-label, noninferiority randomized trial with blinded central outcome adjudication.

Enrollment

1,155

Follow-up

Treatments were administered for 6 months.

Geography

Multinational

Clinical question

Is oral apixaban noninferior to dalteparin for recurrent VTE in patients with cancer, without more major bleeding?

Population

  • Patients with cancer and symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism.

Intervention

Oral apixaban 10 mg twice daily for the first 7 days, then 5 mg twice daily, for 6 months.

Comparator

Subcutaneous dalteparin 200 IU per kilogram once daily for the first month, then 150 IU per kilogram once daily, for 6 months.

Primary outcome

Objectively confirmed recurrent venous thromboembolism during the trial period.

Apixaban was noninferior to dalteparin for recurrent VTE. The interval included 1.0, so this is not superiority.

Hazard ratio / 0.63 / 95% CI 0.37-1.07 / p<0.001

Key results

  • Recurrent VTE: 32 of 576 patients (5.6%) with apixaban versus 46 of 579 (7.9%) with dalteparin; HR 0.63 (95% CI 0.37-1.07; P<0.001 for noninferiority).
  • The recurrent-VTE confidence interval included 1.0, so this is not a superiority result.
  • Major bleeding, the principal safety outcome: 22 patients (3.8%) versus 23 patients (4.0%); HR 0.82 (95% CI 0.40-1.69; P=0.60).

Harms

  • Major bleeding was 3.8% with apixaban versus 4.0% with dalteparin (HR 0.82; 95% CI 0.40-1.69; P=0.60).

Clinical Use

Practice impact

  • Apixaban can replace dalteparin for many patients with cancer-associated proximal DVT or PE who can take oral therapy for 6 months.
  • Do not describe this as fewer recurrences; it met noninferiority.

Applicability

  • Most applicable to patients with cancer and symptomatic or incidental acute proximal DVT or PE.

Limitations

  • Open-label assignment with blinded central outcome adjudication.
  • The primary interval included no difference; the claim is noninferiority, not fewer events.
  • The abstract reports 576 and 579 patients in the outcome denominators and does not state a separate randomized N.

Common misinterpretations

  • Noninferiority is not superiority. The recurrent-VTE HR interval was 0.37 to 1.07.
  • This trial does not show that apixaban prevents more recurrences than dalteparin.
  • Major bleeding was not lower with apixaban; it was similar.

Related evidence

CLOT - Earlier TrialHokusai VTE Cancer - Earlier TrialAMPLIFY - Same Drug Class

Citation

Agnelli G, Becattini C, Meyer G, et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med. 2020;382(17):1599-1607. doi:10.1056/NEJMoa1915103

Oral apixaban was noninferior to subcutaneous dalteparin for the treatment of cancer-associated venous thromboembolism without an increased risk of major bleeding.