Thromboprophylaxis with apixaban prevents VTE in high-risk cancer patients (AVERT); jury still out on rivaroxaban (CASSINI)

Reference

Carrier M, Abou-Nassar K, Mallick R, et al, for the AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2019;380(8):711-719.

Synopsis

Patients with active cancer have a higher risk of VTE. The Khorana score is a validated measure (range 0 – 6), with higher scores indicating a greater risk of VTE. The score is based on type of cancer; body mass index; and baseline hemoglobin, white cell, and platelet counts. In this study, investigators enrolled patients with cancer who were initiating a course of chemotherapy and had a Khorana score of 2 or more. Patients with coagulopathy, severe thrombocytopenia, and renal insufficiency were excluded, among others. Using concealed allocation, patients were randomized to receive apixaban 2.5 mg twice daily (n = 288) or placebo (n = 275) for a treatment period of 180 days. All patients who received at least one dose of the study medication were included in the modified intention-to-treat analysis. The 2 groups were balanced at baseline: mean age was 61 years, 58% were women, and the most common cancers were gynecologic cancers (25%) and lymphomas (25%). Approximately 3% of patients in each group had a previous episode of VTE. The incidence of major VTE (symptomatic or incidentally found proximal deep vein thrombosis or pulmonary embolism) during the 6-month follow-up period was 4.2% in the apixaban group and 10.2% in the placebo group (hazard ratio [HR] 0.41; 95% CI 0.26 - 0.65; P < .001; number needed to treat =17). Patients taking apixaban had more major bleeding events (3.5% vs 1.8%; HR 2.00; 1.01 - 3.95; P = .0046; number needed to treat to harm = 59). In a similar trial comparing rivaroxaban with placebo (CASSINI trial), no significant difference was found in rates of VTE in the 2 groups in the intention-to-treat analysis. However, almost half the patients enrolled in CASSINI prematurely discontinued taking the trial drug. In the per-protocol analysis of this trial, the rate of VTE decreased from 6.4% to 2.6% (HR 0.40; 0.20 - 0.80) and there was no significant difference detected in the rate of major bleeding.