People with cancer, especially when starting chemotherapy, are more likely to develop blood clots in their veins. In this study, patients who had a moderate to high risk of clots on a simple score called the Khorana score were randomly given either a low dose of the blood-thinning tablet apixaban (2.5 mg twice a day) or a placebo (dummy pill). Over 180 days of follow-up, a blood clot occurred in about 4 in every 100 patients in the apixaban group and about 10 in every 100 patients in the placebo group. On the other hand, serious bleeding was more common with apixaban (3.5% versus 1.8%). The decision to take a clot-preventing medicine should be made with the doctor, weighing the risk of clots against the risk of bleeding.
Outpatient with Khorana ≥2 starting chemotherapy with a low bleeding risk
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Apixaban | 2.5 mg twice a day | Oral | Continuous |
In AVERT, VTE was 4.2% vs 10.2% and major bleeding 3.5% vs 1.8%. Interactions and kidney considerations as for the therapeutic apixaban regimen.
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Apixaban 2.5 mg orally twice daily for pharmacological thromboprophylaxis, with 180-day follow-up. Exact treatment duration: further details in the full text.
Double-blind placebo, with 180-day follow-up. Further details in the full text.
Source of the regimen details: Abstract of the paper (N Engl J Med 2019)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Ambulatory patients with cancer who were starting chemotherapy and were at intermediate to high risk of venous thromboembolism (VTE): Khorana score ≥2 (score range 0 to 6; higher scores indicate a greater risk of venous thromboembolism). Other inclusion criteria are not given in the abstract.
Primary efficacy outcome: objectively documented venous thromboembolism during the 180-day follow-up period.
Primary safety outcome: major bleeding episode.
In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and 5 patients (1.8%) in the placebo group (hazard ratio 2.00; 95% CI 1.01 to 3.95; P=0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and 3 patients (1.1%) in the placebo group (hazard ratio 1.89; 95% CI 0.39 to 9.24). Other adverse events are not reported in the abstract.
This trial showed that apixaban 2.5 mg twice daily in ambulatory patients with a Khorana score ≥2 starting chemotherapy reduces venous thromboembolism but is associated with increased major bleeding. After publication of this trial and the CASSINI trial (rivaroxaban), the 2020 update of the ASCO guideline allowed prophylaxis with apixaban, rivaroxaban or low-molecular-weight heparin (LMWH) for selected high-risk ambulatory patients (Key NS et al., J Clin Oncol 2020). The 2022 international ITAC guideline also recommends primary prophylaxis with rivaroxaban or apixaban for ambulatory patients with a Khorana score ≥2 who are not at high risk of bleeding (grade 1B; Farge D et al., Lancet Oncol 2022). The 2.5 mg twice-daily dose in this trial was a prophylactic dose and differs from the DVT/PE treatment dose in the FDA label for apixaban (10 mg twice daily for 7 days, then 5 mg twice daily).
According to the abstract: 11 of the 574 randomised patients were not included in the modified intention-to-treat analysis. Event numbers were small and the confidence interval for the hazard ratio of major bleeding during the treatment period is very wide (0.39 to 9.24). The reduction in venous thromboembolism was accompanied by an increase in major bleeding. Only ambulatory patients with a Khorana score ≥2 starting chemotherapy were included; cancer types, exact treatment duration and other inclusion criteria are not given in the abstract.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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