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Mixed results with direct oral anticoagulants for VTE prevention in cancer

By Bianca Nogrady
Direct oral anticoagulants may reduce the risk of venous thromboembolism (VTE) in some ambulatory patients with cancer, two new studies suggest.

The randomised, placebo-controlled studies, published in The New England Journal of Medicine, examined the effect of either rivaroxaban or apixaban in individuals with cancer at higher risk of VTE.

The apixaban (AVERT) study, which involved 563 patients followed for 180 days, showed a significant 59% reduction in the risk of VTE in patients taking apixaban (2.5 mg twice daily) compared with placebo. The incidence was 10.2% in the placebo group and 4.2% in the apixaban group.

The study also saw a significant twofold increase in the incidence of major bleeding in patients taking apixaban – mainly in participants with gastrointestinal or gynaecological cancers.

In contrast, the rivaroxaban (CASSINI) study, with 841 patients, did not show a statistically significant reduction in the risk of VTE with rivaroxaban treatment (10 mg once daily) compared with placebo, although there were fewer cases of thromboembolism in the intervention arm compared with the placebo arm.

Dr Anoop Enjeti, Senior Staff Specialist in Haematology at Calvary Mater Hospital in Newcastle, told Cardiology Today that the different findings of the two trials may relate to differences in the patient populations. For example, about one-third of the patients in the rivaroxaban study had pancreatic cancer, which is associated with a particularly high risk of VTE, compared with 12% to 14% of patients in the apixaban study.

‘If you choose patients with a really high risk of venous thromboembolism, your ability to reduce the number of events that result maybe different than in a group where the risk is not as high,’ said Dr Enjeti, conjoint senior lecturer at the University of Newcastle and Vice-President of the Thrombosis and Haemostasis Society for Australia and New Zealand. He suggested that at least 40 patients would need to be treated with apixaban to prevent this complication in one patient.

Dr Enjeti commented that current risk prediction scores, such as the Khorana score, did not perform uniformly among the various cancers and did not take chemotherapy regimens into account.

He also noted that the apixaban study used a twice-daily dosing regimen, compared with a once-daily regimen in the rivaroxaban study, and suggested there may be a theoretical benefit to twice-daily dosing.
N Engl J Med 2019; 380: 711-719.
N Engl J Med 2019; 380: 720-728.