Patients with active cancer who developed venous thromboembolism (VTE) and were treated with anticoagulants for at least 6 months, followed by an additional 12 months of low-dose apixaban, experienced similar VTE recurrences and less bleeding as similar patients who received a full dose of the oral blood-thinning medication over the same extended period. These findings from the API-CAT trial were presented at the American College of Cardiology’s Annual Scientific Session (ACC.25) and published in The New England Journal of Medicine.
VTEs are a common complication of cancer and the second leading cause of death in cancer patients after cancer itself. For patients with cancer who develop a VTE, international guidelines recommend treatment with anticoagulants for at least 6 months and for as long as the cancer remains active or cancer treatment continues. Studies have shown that, although the risk of a recurrent VTE diminishes somewhat after 6 months of anticoagulant treatment, patients remain at considerable risk. However, studies also show that anticoagulant treatment may increase patients’ risk for bleeding.
“The best way to prevent a VTE recurrence after 6 months of anticoagulant treatment has not been clear,” said Isabelle Mahé, MD, PhD, Professor of Internal Medicine at the Université Paris Cité, Head of Internal Medicine at Public Assistance Hospitals of Paris, and principal investigator for the study.
Study Details
The aim of the API-CAT trial was to assess whether the lower dose of apixaban was comparable to the full dose in preventing VTE recurrence in patients with active cancer who had completed at least 6 months of treatment with a blood-thinning medication for a VTE. Study investigators also assessed whether the low dose resulted in a decreased risk of bleeding compared with a full dose.
In this randomized, international, double-blinded study, a total of 1,766 patients were prospectively enrolled in 11 countries. Their average age was 67 years and 57% were women. All had active cancer (breast cancer, 22.7%; colorectal cancer, 15.3%; prostate cancer, 9.3%; other cancers, 41.4%); 65.8% had metastatic cancer, and 81.2% were receiving concurrent cancer treatment at inclusion. The median time since the patients’ VTE was 8 months. At enrollment all patients had completed at least 6 months of anticoagulant treatment.
Patients were randomly assigned to be treated with apixaban at either 5 mg (2.5 mg twice daily; the reduced-dose group) or 10 mg (5 mg twice daily; the full-dose group) for an additional 12 months. The study’s primary endpoint was any recurrence of VTE or death from VTE during the treatment period. The key secondary endpoint was a composite of major bleeding and any bleeding that required medical care.
Results
At 12 months, 18 patients in the reduced-dose group and 24 in the full-dose group had had a recurrent VTE (12-months cumulative incidence of 2.1% and 2.8% respectively), a difference that was statistically significant for the noninferiority of the reduced dose compared with the full dose. Clinically relevant bleeding requiring medical care occurred in 102 patients in the reduced-dose group compared with 136 patients in the full-dose group (12-months cumulative incidence of 12.1% and 15.6% respectively), a statistically significant reduction in favor of the reduced dose. Death rates were similar in the two groups (17.7% in the reduced-dose group, 19.6% in the full-dose group).
“We can say that the lower-dose apixaban is both effective and safer than the full dose,” Dr. Mahé said, adding that the results should lead to a guideline update recommending extended treatment with a reduced-dose anticoagulant in this patient group.
Limitations of the study include a lack of guidance on how long anticoagulant treatment should continue beyond the study’s 12-month follow-up period. Secondly, Dr. Mahé said, the study provides no information about possible differences in effectiveness or safety between racial and ethnic groups because France does not permit the collection of data on patients’ race and ethnicity. In addition, patients with brain tumors were excluded from the study, so the results do not apply to them.
Dr. Mahé and her colleagues plan to publish a follow-up analysis of the findings according to the type of cancer patients had and investigate the determinants of bleeding.
Disclosure: The study was funded by the BMS-Pfizer Alliance. For full disclosures of the study authors, visit www.nejm.org.
