Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients With Cancer - CASSINI

Contribution To Literature:

The CASSINI trial failed to show that rivaroxaban was superior to placebo at preventing thromboembolic events.


The goal of the trial was to evaluate rivaroxaban compared with placebo among high-risk ambulatory patients with cancer.

Study Design

  • Randomized
  • Parallel
  • Placebo
  • Double-blind

High-risk ambulatory patients with cancer were randomized to rivaroxaban 10 mg daily (n = 420) versus placebo (n = 421) for up to 180 days. Patients were screened for venous thromboembolism prior to beginning study medication.

  • Total number of enrollees: 841
  • Duration of follow-up: 180 days
  • Mean patient age: 62 years
  • Percentage female: 51%

Inclusion criteria:

  • Patients ≥18 years of age with cancer (solid tumor or lymphoma)

Exclusion criteria:

  • Venous thromboembolism
  • Primary brain tumor or brain metastases
  • Eastern Cooperative Oncology Group performance-status score of ≥3
  • Active bleeding or risk for bleeding

Other salient features/characteristics:

  • Mean intervention period: 4.3 months
  • In the rivaroxaban group, 43.7% discontinued study medication prematurely vs. 50.2% in the placebo group

Principal Findings:

The primary outcome, proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deep vein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, or death from venous thromboembolism at 180 days, occurred in 6.0% of the rivaroxaban group compared with 8.8% of the placebo group (p = 0.10). Thirty-nine percent of primary endpoint events occurred after discontinuation of study medication.

Secondary outcomes:

  • Primary outcome during intervention period: 2.6% for rivaroxaban vs. 6.4% for placebo (p < 0.05)
  • Major bleeding: 2.0% for rivaroxaban vs. 1.0% for placebo (p = not significant [NS])
  • Serious adverse events: 43.3% for rivaroxaban vs. 41.5% for placebo (p = NS)


Among high-risk patients with cancer, rivaroxaban was not superior to placebo at preventing venous thromboembolic events. Bleeding events were low and similar between treatment groups. A large proportion of patients discontinued study medication prematurely, which accounts for the lack of treatment benefit for rivaroxaban.


Khorana AA, Soff GA, Kakkar AK, et al. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients With Cancer. N Engl J Med 2019;380:720-8.

Editorial: Agnelli G. Direct Oral Anticoagulants for Thromboprophylaxis in Ambulatory Patients With Cancer. N Engl J Med 2019;380:781-3.

Clinical Topics: Anticoagulation Management, Cardio-Oncology, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Anticoagulants, Cardiotoxicity, Hemorrhage, Lymphoma, Neoplasms, Primary Prevention, Pulmonary Embolism, Vascular Diseases, Venous Thromboembolism, Venous Thrombosis

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