medwireNews: Patients requiring extended thromboprophylaxis after a first episode of cancer-related venous thromboembolism (VTE) can be given a low dose of the factor X inhibitor apixaban, indicate phase 3 trial findings published in The New England Journal of Medicine.
The API-CAT study authors report noninferiority of apixaban 2.5 mg twice daily versus the standard 5.0 mg twice daily dose for the prevention of recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with active cancer who have already received at least 6 months of anticoagulant therapy.
“Moreover, the reduced dose resulted in a lower incidence of clinically relevant bleeding than the full dose,” say Isabelle Mahé (Université Paris Cité, France) and co-authors.
Discussing the findings in an accompanying editorial, Simon Noble (University of Cardiff, UK) praises the API-CAT investigators for assessing both major and clinically relevant nonmajor bleeding in the trial participants.
“This factor should be regarded as a strength because it recognizes that 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,” he writes.
“Previous research has shown that bleeding that has been classified as nuisance bleeding in clinical trials (and at first glance may appear to be of little relevance) has a considerable effect on patient distress, activities of daily living, and overall emotional health.”
Mahé et al describe their study cohort as being “reflective of patients undergoing extended treatment in routine clinical practice in terms of their age, cancer site, and extent of cancer.”
Specifically, the 1766 participants, who were recruited from 121 centers in 11 countries, were aged a median of 69 years, and 56.6% were women. The most common cancer sites were the breast (22.7%), colon or rectum (15.2%), gynecological system (12.1%), and lung (11.3%).
The patients had experienced PE (75.5%) or proximal lower limb DVT (24.5%) a median of 8.0 months before entering the study and had all received at least 6 months of thromboprophylaxis, most commonly with low molecular weight heparin (54.8%) or a direct oral anticoagulant (43.6%).
Over a median 11.8 months of follow-up, recurrent VTE occurred in 2.1% of the 866 patients who were randomly assigned to receive reduced-dose apixaban and 2.8% of the 900 patients who instead received full-dose apixaban. The adjusted subhazard ratio of 0.76 was within the prespecified noninferiority margin of 2.0 for the upper boundary of the two-sided confidence interval, the researchers report.
Clinically relevant bleeding was reported for 12.1% of patients given reduced-dose apixaban versus 15.6% of those treated with the full dose, giving a significant adjusted subhazard ratio of 0.75 in favor of the 2.5 mg dose.
There was no significant difference between the reduced-dose and full-dose groups in the rates of major bleeding (2.9 vs 4.3%), clinically relevant nonmajor bleeding (10.0 vs 12.3%), or mortality (17.7 vs 19.6%, two fatal bleeding episodes in each group).
Overall, a comparable 19.9% of patients in the reduced-dose group and 22.1% of those in the full-dose group experienced the composite endpoint of recurrent symptomatic VTE, major bleeding, or death from any cause. One or more serious adverse events were reported for 39.8% of patients given the reduced dose and 43.8% of those given the full dose.
Noble summarizes that 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.”
He adds: “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.”
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N Engl J Med 2025; doi:10.1056/NEJMoa2416112
N Engl J Med 2025; doi:10.1056/NEJMe2503460
