Low-dose apixaban for extended anticoagulation may be option for preventing cancer-related VTE
Key takeaways:
- Continued anticoagulation is recommended for patients with active cancer and/or ongoing cancer treatment.
- Extended treatment with low-dose apixaban was noninferior to a full dose for preventing cancer-related VTE.
CHICAGO — For patients with cancer requiring extended anticoagulant therapy, a strategy of reduced-dose apixaban was noninferior to full-dose apixaban for prevention of cancer-associated recurrent venous thromboembolism.
Reduced-dose apixaban also resulted in a lower incidence of clinically relevant bleeding.
Results of the randomized, double-blind, noninferiority API-CAT trial evaluating regular vs. low-dose apixaban (Eliquis, Bristol Myers Squibb/Pfizer) in patients with cancer and proximal deep vein thrombosis or pulmonary embolism were presented at the American College of Cardiology Scientific Session and simultaneously published in The New England Journal of Medicine.“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,” Isabelle Mahé, MD, PhD, cardiologist and professor of internal medicine at Université Paris Cité and head of internal medicine at Louis Mourier, Assistance Publique Hôpitaux de Paris in Paris, said during a press conference. “International guidelines suggest continuing anticoagulant therapy for as long as the cancer remains active or cancer treatment is ongoing. ... The optimal apixaban dose regimen to take beyond 6 months is unknown due to the lack of randomized control trial to date.”
Mahé and colleagues randomly assigned 1,766 consecutive patients who previously underwent 6 months of anticoagulation to twice-daily apixaban 2.5 mg or 5 mg for 12 months (median age, 69 years; 43% men; 18.5% with history of VTE). The primary outcome was fatal or nonfatal recurrent VTE. The key secondary outcome was clinically relevant bleeding, which was defined as a composite of major or clinically relevant nonmajor bleeding during 12 months of follow-up.
The most common cancer type was breast cancer (22.7%), followed by colon or rectal cancer (15.2%), gynecologic cancers (12.1%) and lung cancer (11.3%).
The primary index event in three-quarters of patients was lower-limb proximal DVT with PE. All patients were randomly assigned to either treatment strategy at a median of 8 months after the index event. Median duration of the study drug was 11.8 months.
the cumulative incidence of recurrent VTE was 2.1% in the reduced-dose group compared with 2.8% in the full-dose group (adjusted subhazard ratio = 0.76; 95% CI, 0.41-1.41; P for noninferiority = .001).
The cumulative incidence of clinically relevant bleeding was 12.1% in the reduced-dose group compared with 15.6% in the full-dose group (adjusted subhazard ratio = 0.75; 95% CI, 0.58-0.97; P for superiority = .03), according to the presentation.
Moreover, the cumulative incidence of all-cause death in the reduced-dose apixaban group was 17.7% compared with 19.6% in the full-dose group (aHR = 0.96; 95% CI, 0.86-1.06; P = .42).
“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,” Mahé said during the press conference. “In addition, the reduced dose resulted in a lower incidence of clinically relevant bleeding. 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.”
During a discussion after the press conference, Diego Sadler, MD, FACC, section head of cardio-oncology at Cleveland Clinic Weston Hospital, discussed the API-CAT trial results and its potential impact on current cardio-oncology practice.
“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. This impacts a large population just in the United States. There are 2 million active new cancers per year,” Sadler said. “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 a related editorial published in NEJM, Simon Noble, MD, the Marie Curie Chair in Supportive and Palliative Medicine and co-director of the Marie Curie Palliative Care Research Centre in the division of population medicine at Cardiff University, U.K., highlighted the importance of targeting patient-relevant outcomes in trials such as API-CAT.
“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,” Noble wrote. “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.”
References:
- Mahé I, et al. N Engl J Med. 2025;doi:10.1056/NEJMoa2416112.
- Noble S. N Engl J Med. 2025;doi:10.1056/NEJMe2503460.
Perspective
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This was an important study that is likely to have immediate practice-changing implications.
First, it is interesting that it shows us we can use a low-dose apixaban strategy, or you could more generally say a "half-dose" direct oral anticoagulant (DOAC) strategy for secondary prevention of VTE. Doing so has some benefits of lower bleeding risk compared with the full-dose strategy. This is the first time we've seen that. If you go back to the initial studies that looked at that half-dose strategy, you didn't see any bleeding difference between the full- and half-dose DOAC strategies. API-CAT provides for us that evidence and helps us tell patients why we're thinking about using this strategy.
Second, it confirms that we can use this strategy in patients in whom we already knew we wanted to continue long-term anticoagulation. If you go back to the EINSTEIN-CHOICE and AMPLIFY extension (AMPLIFY-EXT) trials, those were done in patients in whom there was equipoise as to whether you needed to continue beyond the initial 6-month period. Now, we have the data to tell us, yes, you should continue using these drugs even in those you knew you were going to use this therapy long term. Now you can use a half-dose approach.
Third, we were all concerned about half-dose strategies in a cancer VTE population, because that's a very high-risk group for recurrence. This provides us reassurance to say, “Nope, these drugs are efficacious.”
API-CAT can teach us things that are going to help us in our clinical practice.
One remaining question is: Can we extrapolate the results of API-CAT, which used a half-dose apixaban strategy, to the other DOACs, such as rivaroxaban, which is commonly used. We also need to look closer into some of those cancer subtypes. Cancers at highest risk for VTE include pancreatic cancers. That still is a question that needs to be explored. Then, for how long do we need to treat these patients? Most of us think that after that initial 6 months, you continue to treat. If they're on any sort of a cancer therapy, does that mean a minimum of another 6 months? Is it 12 months? How long do you go? These are questions we are going to need to keep exploring.
Vascular Medicine Specialist
University of Michigan Health
President
Anticoagulation Forum
Co-Director
Michigan Anticoagulation Quality Improvement Initiative
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Mahé I, et al. Joint American College of Cardiology/Journal of American College of Cardiology late-breaking clinical trials. Presented at: American College of Cardiology Scientific Session; March 29-31, 2025; Chicago (hybrid meeting).
