Patients with active cancer who developed a blood clot, or venous thromboembolism (VTE), and were treated with blood-thinning medication for at least six 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).
VTEs are a common complication of cancer and the second leading cause of death in cancer patients after cancer itself. Cancer cells release substances that make it easier for blood clots to form. Cancer treatment can also cause inflammation in blood vessels and elevate risk for blood clots. Additionally, surgery limits patients' mobility and the use of invasive devices also helps to explain the risk of VTE.
For patients with cancer who develop a VTE, international guidelines recommend treatment with anticoagulants, or blood-thinning medication, for at least six 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 six 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 six months of anticoagulant treatment has not been clear."
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
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 six 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 (cancer that had spread from the site where it started to other parts of the body), and 81.2% were receiving concurrent cancer treatment at inclusion. The median time since the patients' VTE was eight months. At enrollment all patients had completed at least six months of anticoagulant treatment.
Patients were randomly assigned to be treated with either 5 mg (2.5mg twice daily; the reduced-dose group) or 10 mg (5 mg twice daily; the full-dose group) of apixaban for an additional 12 months. Neither patients nor their doctors knew which dose patients were receiving until the end of the trial. All deaths, suspected VTE recurrences and suspected bleeding episodes during the trial were reviewed by an independent group of physicians who also were unaware of which treatment patients were receiving. 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.
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 non-inferiority 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," 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, 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.
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.
The study was funded by the BMS-Pfizer Alliance. Bristol-Myers Squibb provided the apixaban free of charge. It was an investigator- sponsored study coordinated by Assistance Publique des Hôpitaux de Paris (AP-HP). The funder of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report.
This study was simultaneously published online in the New England Journal of Medicine at the time of presentation.
Micro-ultrasound proves as effective as MRI in prostate cancer diagnosis