Patients with active cancer who experienced blood clots, known medically as venous thromboembolism (VTE), showed favorable outcomes with a lower dose of apixaban. This was demonstrated by the recent API-CAT trial, which found that a reduced dose effectively prevented recurrence of VTE while substantially lowering the risk of bleeding, compared to the standard higher dose.
Venous thromboembolism—a significant concern for cancer patients
VTEs are notably common among cancer patients and represent the second leading cause of death in this population, exceeded only by cancer itself. Cancer contributes to VTE risk through multiple mechanisms. Cancer cells release substances that encourage blood clot formation, and various cancer treatments can induce inflammation within blood vessels, further elevating clot risks. Additionally, surgeries and the use of invasive medical devices often reduce patient mobility and compound clot risks.
READ MORE: AI Breakthrough Promises Faster, Cheaper Mosquito Identification
Guidelines internationally recommend treating cancer patients who develop VTE with anticoagulant therapy (blood thinners) for at least six months, continuing treatment as long as the cancer remains active or treatment persists. While the risk of recurrent VTE typically diminishes after six months, the threat remains significant, and extended anticoagulant treatment itself can pose a considerable risk of bleeding.
“The best way to prevent VTE recurrence after six months of anticoagulant treatment has not been clear,” noted Isabelle Mahé, MD, PhD, principal investigator of the API-CAT trial and professor of internal medicine at Université Paris Cité.
Objectives and methods of the API-CAT trial
The API-CAT trial aimed to compare the efficacy of reduced-dose versus full-dose apixaban in preventing VTE recurrence among cancer patients who had already completed at least six months of anticoagulant therapy.
In this randomized, international, double-blinded trial, researchers enrolled 1,766 patients across 11 countries. Participants had an average age of 67, with 57% women. All had active cancer, including breast (22.7%), colorectal (15.3%), prostate (9.3%), and various other cancers (41.4%). Metastatic disease was present in 65.8% of participants, and 81.2% were receiving concurrent cancer treatments. The median time since their initial VTE event was approximately eight months.
Participants were randomly assigned to either a reduced dose of apixaban (2.5 mg twice daily) or the standard full dose (5 mg twice daily) for 12 months. Neither patients nor their physicians knew which dose was being administered during the trial. Independent physicians, blinded to dosage allocation, reviewed all cases of VTE recurrence, bleeding events, and deaths.
The trial’s primary endpoint focused on recurrence of VTE or death from VTE, while the key secondary endpoint assessed major bleeding and any bleeding events requiring medical intervention.
Key findings confirm efficacy and enhanced safety of lower dose
After 12 months, VTE recurrence occurred in 18 patients (2.1%) in the reduced-dose group compared to 24 patients (2.8%) in the full-dose group. This outcome established the reduced dose as non-inferior to the standard dose for preventing recurrent VTE.
Importantly, significant bleeding events requiring medical care were substantially fewer in the reduced-dose group, affecting 102 patients (12.1%), compared with 136 patients (15.6%) in the full-dose group. This marked a statistically significant improvement in safety with the lower dosage. Mortality rates were comparable between groups—17.7% in the reduced-dose group and 19.6% in the full-dose group.
“The lower-dose apixaban is both effective and safer than the full dose,” Dr. Mahé concluded. These compelling results are expected to inform updates in clinical guidelines recommending lower-dose extended anticoagulant therapy for cancer patients.
Limitations and future research directions
Despite the encouraging results, the study acknowledged several limitations. The duration of optimal anticoagulant therapy beyond the trial’s 12-month follow-up remains unclear. Additionally, the trial lacked data on potential differences in treatment efficacy or safety among racial and ethnic groups, as French regulations restrict collection of such demographic information.
Furthermore, patients with brain tumors were excluded from the study, limiting the generalizability of results to this subgroup.
Future analyses planned by Mahé and colleagues will explore outcomes based on cancer types and investigate factors influencing bleeding risks.
Study funding and independence
The API-CAT trial was funded by the BMS-Pfizer Alliance, with Bristol-Myers Squibb providing apixaban free of charge. The study was investigator-sponsored, coordinated by Assistance Publique des Hôpitaux de Paris (AP-HP). Importantly, the funding bodies had no involvement in study design, data collection, data analysis, interpretation, or manuscript preparation.
These groundbreaking findings were presented at the American College of Cardiology’s Annual Scientific Session (ACC.25) and simultaneously published in the New England Journal of Medicine.
