Content area
Abstract
Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis. We conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate-to-high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow-up period of 180 days. The main safety outcome was a major bleeding episode. Of the 574 patients who underwent randomization, 563 were included in the modified intention-to-treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P<0.001). In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 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 in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24). Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo. (Funded by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance; AVERT ClinicalTrials.gov number, NCT02048865.)
Details
1 From the Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa (M.C., R.M., G.G., G.L.G., D.S., T.R., M.R., D.W., P.S.W.), Centre Intégré de Santé et des Services Sociaux de l’Outaouais, Gatineau, QC (K.A.-N.), Jewish General Hospital, Lady Davis Institute for Medical Research, McGill University, Montreal (V.T.), Nova Scotia Health Authority, Halifax (S. Shivakumar), Lakeridge Health, Oshawa, ON (A.S.), William Osler Health Centre, Brampton, ON (P.K.), Sault Area Hospital, Sault Ste. Marie, ON (D.H., S. Spadafora), Hôpital Régional de Rimouski, Rimouski, QC (K.M.), Markham Stouffville Hospital, Markham, ON (M.T.), Kingston General Hospital, Kingston, ON (A.T.), University of British Columbia, British Columbia Cancer Agency, Vancouver (A.Y.Y.L.), Hamilton Health Sciences, Hamilton, ON (P.L.G.), London Health Sciences Centre, London, ON (A.L.-L.), and Royal Victoria Regional Health Centre, Barrie, ON (R.E.-M.) — all in Canada.