Written by Peter Liu
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For secondary prophylaxis of cancer-associated venous thromboembolism (VTE), reduced-dose apixaban is noninferior in terms of VTE recurrence and superior in terms of bleeding risk.
Reduced-dose apixaban prevents VTE in both cancer and noncancer patients, with lower bleeding risk
First, some context:
- After acute treatment of VTE over 3-6 months, many patients benefit from long-term anticoagulation for secondary prophylaxis of VTE. This is frequently referred to as “extended treatment” of VTE.
- The AMPLIFY-EXT RCT showed reduced-dose apixaban (2.5 mg BID) is effective for extended VTE treatment, though the RENOVE trial did not clearly confirm noninferiority to standard dosing.
- The ONCO PE Trial recently demonstrated that many patients with malignancy-related PE benefit from extending anticoagulation duration.
The API-CAT RCT evaluated reduced-dose (2.5 mg) vs. full-dose (5 mg) apixaban for extended treatment of cancer-associated VTE in 1,766 patients after 6 months of anticoagulation. Over a median of 11.8 months, recurrent VTE occurred in 2.1% (reduced-dose) vs. 2.8% (full-dose), confirming noninferiority (subhazard ratio, SHR 0.76; 95%CI 0.41–1.41; p=0.001). Clinically relevant bleeding was significantly lower with reduced-dose therapy (12.1% vs. 15.6%; SHR 0.75; 95%CI 0.58–0.97; p=0.03). These results establish reduced-dose apixaban as a valid option for extended anticoagulation in malignancy-associated VTE.
Importantly for atrial fibrillation, off-label reduced-dosing of apixaban remains controversial, with evidence associating this practice with increased mortality. The benefits of reduced-dose apixaban found in API-CAT do not easily generalize to atrial fibrillation.
How does this change my practice?
For most patients with active cancer, VTE, and acceptable bleeding risk, I strongly favor extended anticoagulant therapy for secondary prophylaxis of VTE. In cancer patients that would do well with twice-daily dosing, I personally favor reduced-dose apixaban. The results of this trial cannot be generalized to atrial fibrillation patients, as linked above.
Source
Extended Reduced-Dose Apixaban for Cancer-Associated Venous Thromboembolism. N Engl J Med. 2025 Apr 10;392(14):1363-1373. doi: 10.1056/NEJMoa2416112. Epub 2025 Mar 29. PMID: 40162636
