Low-Dose Apixaban Best for Long-Term Use in Cancer

Extended therapy with reduced-dose apixaban is just as effective as the high dose in preventing recurrent venous thromboembolism (VTE) in patients with active cancer who completed at least 6 months of anticoagulant treatment after a clot, and results in a lower rate of clinically relevant bleeding, the API-CAT trial shows.

“Our results indicate that cancer patients should receive a reduced dose of apixaban for extended venous thromboembolism prophylactic treatment,” said lead investigator Isabelle Mahé, MD, PhD, from Université Paris Cité, France.

“We think these findings will result in a change in guidelines and clinical practice,” she explained during her presentation of the API-CAT trial at the American College of Cardiology (ACC) Scientific Session 2025. The results were simultaneously published online in the New England Journal of Medicine.

“This is the first large study to look at the appropriate dose of anticoagulant for long-term VTE prophylaxis in cancer patients, and it has shown a clear result,” said Diego Sadler, MD, head of the cardio oncology section at Cleveland Clinic Florida in Weston, who is chair-elect of the ACC Cardio-Oncology Council, during a news conference.

“We can use a lower dose of anticoagulant and offer safe and effective prophylactic treatment. This is excellent news for cardiologists and oncologists,” he added.

The study findings will have an impact on a large population. “Just in the United States, there are 2 million new cancers per year, giving 20 million cancer survivors. A lot of these patients have a high incidence of thrombotic events, and they struggle with a high risk for bleeding on high doses of anticoagulants,” Sadler pointed out.

VTE: Number 2 Cause of Death in Cancer

VTE is a common complication of cancer and the second-leading cause of death in patients with cancer, after cancer itself. 

“Patients with cancer now have many months and years of life expectancy and the risk of VTE recurrences remains substantial over this time,” Mahé explained.

Although international guidelines suggest that anticoagulant treatment be continued for as long as cancer is active and cancer treatment is ongoing, the optimal dose of anticoagulants beyond 6 months is unknown because of the lack of data from randomized controlled trials, she noted.

The API-CAT trial was conducted to look at this issue.

The trial assessed 1766 patients from 11 countries with active cancer, 65.8% of whom had metastatic cancer and 81.2% of whom were receiving cancer treatment at enrollment. The most frequent sites of the primary cancer were the breast (22.7%), colon or rectum (15.2%), gynecologic system (12.1%), and lung (11.3%). Patients had also experienced a proximal deep vein thrombosis or pulmonary embolism and had completed at least 6 months of initial anticoagulant therapy.

Participants were randomized to oral apixaban at a reduced dose (2.5 mg) or a full dose (5.0 mg) twice daily for 12 months.

The primary outcome was centrally adjudicated fatal or nonfatal recurrent VTE after 12 months of treatment. The aim of the study was to show noninferiority of the lower dose.

Recurrent VTE was experienced by 18 patients (cumulative incidence, 2.1%) in the reduced-dose group and in 24 patients (cumulative incidence, 2.8%) in the full-dose group (adjusted subhazard ratio, 0.76; 95% CI, 0.41 – 1.41). This was significant for noninferiority (P = .001).

Clinically relevant bleeding was significantly lower in the reduced-dose group than in the full-dose group (102 vs 136 patients; cumulative incidence, 12.1% vs 15.6%; adjusted subhazard ratio, 0.75; 95% CI, 0.58 – 0.97; P = .03).

Mortality rate was similar in the reduced-dose and full-dose groups (17.7% vs 19.6%).

“We can say that lower-dose apixaban is both effective and safer than the full dose,” Mahé said.

“A Seminal and Practice-Changing Study”

Bonnie Ky, MD, professor of cardio-oncology at the University of Pennsylvania in Philadelphia, congratulated Mahé for “this truly seminal and, I believe, practice-changing study.”

Cancer significantly increases the risk for VTE, and because there have been substantial advances in cancer treatment and improved survival rates, “cancer is increasingly becoming a chronic disease, and we need to mitigate these comorbid conditions that impact this growing population,” she explained during the late-breaking clinical trial session.

The recurrent VTE rate in the trial was low overall, although the bleeding rate was a little higher than in other studies. However, “I think these findings will inform guidelines and are going to change clinical practice, and I think it will result in improvement in clinical outcomes,” Ky said.

“We have to ask why” the lower dose is better at preventing VTE, said Kim Eagle, MD, from the University of Michigan School of Public Health in Ann Arbor. “I’m wondering if GI bleeding led to discontinuation of the higher dose, so that then the patients weren’t on any anticoagulation.”

The investigators are working to look into this, Mahé reported. “The risk of VTE recurrence was low for this population with advanced cancer, but yes, the low dose of apixaban was very effective at reducing the risk,” she said.

A Chronic Condition

It is important to treat VTE as a chronic condition, said Joshua Beckman, MD, from the University of Texas Southwestern Medical Center in Dallas.

“We are all very used to the chronic treatment of arterial disease. This is another piece of really important evidence showing that when an event occurs in the veins, it is the beginning of a chronic disease that must be treated for a long period of time. We’ve seen this in extended trials in patients without cancer, and now it has been nicely confirmed in patients with cancer. We cannot think of venous thromboembolism as a one and done. It is actually the beginning of long-term therapy and care,” Beckman said.

The API-CAT trial “establishes apixaban, administered at a 2.5-mg twice-daily dose, as an appropriate regimen for anticoagulation beyond the first 6 months in patients with cancer,” writes Simon Noble, MBBS, from Cardiff University, UK, in an editorial accompanying the published study.

The trial set a low bar for reporting clinically relevant nonmajor bleeding, which Noble suggests is a strength because it recognizes that, in this trial population, the effect of bleeding on overall quality of life is particularly important and has a considerable effect on patient distress, activities of daily living, and overall emotional health.

“The additional value of the results of the API-CAT trial lies with the investigators’ decision to report patient-relevant bleeding outcomes. This reporting provides clinicians with much-needed information for them to engage in meaningful dialogue with patients in order to make anticoagulation decisions that are based on patients’ values and preferences,” he adds.

The API-CAT study was funded by the Bristol Myers Squibb (BMS) – Pfizer Alliance. BMS provided apixaban free of charge. Mahé has reported receiving consultancy fees from AstraZeneca and research grants and speakers fees from BMS-Pfizer and Leo Pharma.