Real-world outcomes of extended reduced-dose apixaban versus full-dose apixaban in cancer-associated venous thromboembolism

Abstract Introduction Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality among patients with active cancer. Current guidelines from the American Society of Clinical Oncology (ASCO) recommend extended anticoagulation to prevent recurrent VTE in patients with active cancer and established VTE. While the recent API-CAT trial demonstrated that reduced-dose apixaban was noninferior to full-dose apixaban for extended anticoagulation beyond at least 6 months of full-dose anticoagulation, real-world evidence guiding optimal dosing strategies in patients with active cancer remains limited. Our study aimed to evaluate the real-world outcomes of reduced- versus full-dose apixaban for extended anticoagulation in patients with active cancer-associated VTE. Method A retrospective cohort study was conducted using TriNetX, a global federated health research network that provides access to electronic medical records from approximately 132 million patients, primarily in the United States. Adult patients (≥18 years) diagnosed with lung cancer, colorectal cancer, breast cancer and prostate cancer who received chemotherapy, radiation therapy, targeted therapy or hormonal therapy between January 1, 2015, and January 1, 2024, were identified using ICD-10-CM codes. Patients were categorized into two cohorts: patients who received apixaban 2.5 mg twice daily (BID) and patients who received apixaban 5 mg BID after an initial 6 months of full-dose anticoagulation. Propensity score matching (1:1) using nearest neighbor matching with a 0.1 pooled standard deviation caliper was performed for demographics, comorbidities including obesity and prior history of VTE, medications and performance status. Study outcomes included 1-year rates of major bleeding, gastrointestinal (GI) bleeding, venous thromboembolism, all-cause hospitalization and mortality. Statistical analyses were conducted on the TriNetX platform, with significance set at P<0.05 (two-sided). TriNetX calculates hazard ratios (HRs) and cumulative incidences (CIs) using R survival package version 3.2-3 with the proportional hazard assumption tested using Schoenfeld residuals. This study did not require Institutional Review Board review or informed consent due to the use of de-identified data. Results Our study identified 54,936 patients, including 1,393 patients who received reduced-dose apixaban and 53,543 who received full-dose apixaban. After propensity score matching (PSM), 1,393 patients remained in the reduced-dose group (mean age 72.9 ± 11.5 years; 53.2% female; 74.6% White, 15.3% African American, 1.4% Asians) and 1,393 patients remained in the full-dose group (mean age 72.7 ± 10.9 years of age; 53.6% female; 74.4% White, 16.2% African American, 1.4% Asians). Patients who received reduced-dose apixaban demonstrated a lower risk of major bleeding (HR 0.80; 95% CI, 0.67–0.94), GI bleeding (HR 0.68; 95% CI, 0.51–0.91), and all-cause hospitalization (HR: 0.75; 95% CI: 0.68–0.82) compared with patients receiving full-dose apixaban. Reduced-dose therapy was not associated with higher risk of recurrent VTE compared to full-dose therapy (HR: 0.42; 95% CI: 0.37–0.47). There was no significant difference observed in all-cause mortality between these two treatment groups (HR: 0.98; 95% CI: 0.84–1.15) between the two treatment groups. ConclusionIn this real-world analysis of patients with active cancer receiving extended anticoagulation, reduced-dose apixaban was associated with a lower risk of major bleeding, GI bleeding and all-cause hospitalization compared to full-dose apixaban, without an increased risk of recurrent VTE. These findings suggest that reduced-dose apixaban may offer a favorable balance of efficacy and safety during the extended treatment phase in this patient population. These findings additionally suggest that dosing strategy may not be the primary determinant of VTE recurrence in patients with cancer receiving apixaban, and that baseline bleeding risk and individualized risk assessments should play a central role in informing anticoagulation strategies. Limitations of our study include its retrospective design, which inherently limits the ability to capture undocumented interruptions in anticoagulation therapy and medication nonadherence.