The API-CAT trial has demonstrated that reduced-dose apixaban is both effective and safer than standard dosing for extended anticoagulation in cancer patients with venous thromboembolism (VTE), according to results presented at the American College of Cardiology Scientific Session and simultaneously published in The New England Journal of Medicine.
In this randomized, double-blind, noninferiority trial, researchers found that a 2.5mg twice-daily dose of apixaban (Eliquis) was noninferior to the standard 5mg twice-daily regimen for preventing recurrent VTE in cancer patients who had already completed at least six months of anticoagulation therapy.
Study Design and Patient Population
The API-CAT trial enrolled 1,766 patients with active cancer who had experienced proximal deep vein thrombosis (DVT) or pulmonary embolism (PE). Participants were randomly assigned to receive either reduced-dose apixaban (2.5mg twice daily, n=866) or full-dose apixaban (5mg twice daily, n=900) for 12 months.
The study population had a median age of 69 years, with 43% being male. Notably, 18.5% had a history of previous VTE. The most common cancer types among participants were:
- Breast cancer (22.7%)
- Colorectal cancer (15.2%)
- Gynecologic cancers (12.1%)
- Lung cancer (11.3%)
- Prostate cancer (9.3%)
Most patients (65.8%) had metastatic disease, highlighting the advanced cancer status of the study population. The primary index event in approximately 75% of patients was lower-limb proximal DVT with PE, and all patients were randomized at a median of 8 months after their index thrombotic event.
Key Findings on Efficacy and Safety
The primary efficacy outcome—recurrent fatal or nonfatal VTE—occurred in 2.1% of patients in the reduced-dose group compared to 2.8% in the full-dose group (adjusted subhazard ratio = 0.76; 95% CI, 0.41-1.41; P for noninferiority = .001).
More importantly, the reduced-dose strategy demonstrated superior safety outcomes. The cumulative incidence of clinically relevant bleeding was significantly lower in the reduced-dose group at 12.1% versus 15.6% in the full-dose group (adjusted subhazard ratio = 0.75; 95% CI, 0.58-0.97; P for superiority = .03).
The specific bleeding outcomes showed consistent benefits with the reduced dose:
- Major bleeding: 2.9% vs. 4.3% (favoring reduced dose)
- Major gastrointestinal bleeding: 1.4% vs. 2.9% (favoring reduced dose)
All-cause mortality was similar between groups, with 17.7% in the reduced-dose arm and 19.6% in the full-dose arm (adjusted hazard ratio = 0.96; 95% CI, 0.86-1.06; P = .42).
Clinical Implications
"In patients with active cancer who have completed at least 6 months of anticoagulant treatment, extended treatment with reduced-dose apixaban was non-inferior to full-dose apixaban to prevent recurrent venous thromboembolism," said Dr. Isabelle Mahé, the study's lead investigator and professor of internal medicine at Université Paris Cité.
Dr. Mahé emphasized the changing landscape of cancer-associated thrombosis management: "The life expectancy of patients with cancer-associated thrombosis is improving... The risk of recurrent VTE declines over time, whereas the risk of bleeding remains substantial."
Current international guidelines recommend continuing anticoagulant therapy for as long as cancer remains active or cancer treatment is ongoing. However, until now, the optimal apixaban dosing regimen beyond six months was unknown due to lack of randomized controlled trial data.
Expert Commentary
Diego Sadler, MD, FACC, section head of cardio-oncology at Cleveland Clinic Weston Hospital, called the results practice-changing: "This is a very important first large study in this area with low-dose apixaban, so it can be practice-changing. This is excellent news for cardiologists and oncologists."
Dr. Sadler highlighted the widespread impact of these findings: "This impacts a large population just in the United States. There are 2 million active new cancers per year. A lot of these patients have a high incidence of thrombotic events and they struggle with a high risk for bleeding... With this study, now we can show that we can go with a lower dose, [which is] as effective as a higher dose, with much less bleeding."
In an accompanying editorial in NEJM, Simon Noble, MD, from Cardiff University, emphasized the importance of the patient-centered approach in the trial: "In this trial population, in which more than 80% of the patients had an incurable disease, the effect of bleeding on overall quality of life will often take primacy over whether the bleeding is classified as major or nonmajor."
Balancing Efficacy and Safety in Cancer Patients
The API-CAT trial addresses a critical clinical challenge in managing cancer patients who require long-term anticoagulation. As cancer treatments become more effective and patients live longer with their disease, the risk of thrombotic complications remains significant, but so does the risk of bleeding with anticoagulant therapy.
The findings suggest that after an initial period of full-dose anticoagulation (at least 6 months), transitioning to a reduced dose of apixaban provides comparable protection against recurrent VTE while significantly reducing bleeding complications. This approach may be particularly valuable for patients with metastatic disease or those on ongoing cancer treatments that increase bleeding risk.
Dr. Mahé concluded: "We think that our result will result in a change in the guidelines and result in the use of the reduced-dose apixaban for our patients under extended treatment."
