The CASSINI trial previously showed that thromboprophylaxis with rivaroxaban did not decrease venous thromboembolism (VTE) events at 180 days in ambulatory cancer patients who were at a high risk for developing VTE. The trial results, originally published in the New England Journal of Medicine earlier this year, were the topic of a recent article in the ACP Journal Club of Annals of Internal Medicine.1,2

In the ACP Journal Club article, Andrea Cervi, MD, and James Douketis, MD, McMaster University, Hamilton, Canada, pointed out the results of the primary intention-to-treat analysis, which found that rivaroxaban was not superior to placebo, did not align with those of the more conventional on-treatment analysis, which concluded that rivaroxaban was superior to placebo. They reasoned that the high discontinuation rates for the 2 groups — 44% for the rivaroxaban arm and 50% for the placebo arm — “probably” explained this disagreement.

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As for safety outcomes, rivaroxaban was not found to be associated with a higher rate of bleeding compared with placebo. Drs. Cervi and Douketis described this as “reassuring given that direct oral anticoagulants (DOACs) increase bleeding in patients with gastrointestinal cancer.”

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Drs. Cervi and Douketis also discussed the CASSINI trial results in the context of the AVERT trial, which reported that thromboprophylaxis with apixaban in at-risk cancer patients in the outpatient setting reduced VTE events.

“Although CASSINI showed a benefit only if patients stayed on treatment, the totality of evidence from the CASSINI and AVERT trials suggests a role for DOAC prophylaxis in select patients at high risk for VTE, such as those with pancreatic cancer,” Drs. Cervi and Douketis wrote. They cautioned that “further evidence is needed for common cancers” before DOAC prophylaxis can be recommended.


  1. Cervi A, Douketis J. In high-risk patients with cancer, thromboprophylaxis with rivaroxaban did not reduce VTE events at 180 days. Ann Intern Med. 2019;170(12):JC67.
  2. Khorana AA, Soff GA, Kakkar AK, et al; CASSINI Investigators. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med. 2019;380(8):720-728.