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Presentation Details
| Rethinking Extended Anticoagulation in Cancer: Is Less More? A Systematic Review and Meta-Analysis of Clinical Trials Ursula Medeiros Araujo de Matos1, Eduardo Dan Itaya1, Moana Divina da Silva Santiago1, Patrick Froelich Meldola2, Pedro L Lage Bodour Danielian3, Gustavo J Silva Sanchez1, Swarup Kumar4, Ritika Vankina4. 1Internal Medicine Department, University of Connecticut, Farmington, CT, USA.2Federal University of Santa Catarina, School of Medicine, Santa Catarina, Brazil.3Harvard T.H.Chan School of Public Health, Boston, MA, USA.4Hematology and Oncology Department, University of Connecticut, Farmington, CT, USA |
Abstract
Background:
Cancer-associated thrombosis (CAT) is a major contributor to morbidity and mortality, with high rates of recurrence and clinically relevant bleeding. Extended anticoagulation reduces recurrent venous thromboembolism (VTE) by >80%, yet maintaining full-dose therapy may increase bleeding risk in cancer patients. Reduced-dose direct oral anticoagulants (DOACs) have recently been evaluated as a potential strategy to balance thrombotic and hemorrhagic risks beyond the initial 6-month treatment phase. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of reduced-dose versus standard-dose DOACs in the extended treatment of CAT.
Methods:
A systematic search of PubMed, Embase, and Scopus through June 2025 identified RCTs evaluating reduced-dose versus standard-dose regimens of apixaban rivaroxaban or edoxaban in adults with active cancer and prior VTE who had completed ≥6 months of anticoagulation. Five RCTs met eligibility criteria. Outcomes included recurrent VTE, major bleeding, clinically relevant non-major bleeding (CRNMB), composite bleeding, and all-cause mortality. Additional analyses were performed for VTE subtype and sites of bleeding. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random-effects models. Risk of bias was assessed using the Cochrane RoB 2 tool.
Results:
Five trials comprising 2,709 patients were included: 1,408 received reduced-dose DOACs and 1,301 standard-dose DOACs. We found that recurrent VTE did not differ significantly between reduced and standard-dose groups (OR 0.66, 95% CI 0.40–1.11; I²=19%). When stratified by VTE subtype, results were similar, with no significant differences for pulmonary embolism (OR 0.89, 95% CI 0.42–1.88), upper-extremity DVT (OR 0.35, 95% CI 0.04–3.33), or lower-extremity DVT (OR 1.14, 95% CI 0.48–2.71). All-cause mortality also did not differ between reduced and standard-dose therapy (OR 1.09, 95% CI 0.76–1.55; I²=39%). In terms of safety outcomes, major bleeding was less frequent with reduced-dose DOACs (OR 0.67, 95% CI 0.44–1.01; I²=0%), though not statistically significant. CRNMB was significantly reduced in the reduced-dose group (OR 0.73, 95% CI 0.56–0.95; I²=0%). Composite bleeding (major plus CRNMB) was also significantly lower (OR 0.68, 95% CI 0.54–0.85; I²=0%). Bleeding subtype analyses (gastrointestinal, genitourinary, epistaxis, intracranial) demonstrated consistently lower event rates with reduced-dose therapy, though differences were not statistically significant.
Conclusion:
In cancer patients requiring extended anticoagulation beyond six months, reduced-dose DOACs provide comparable protection against recurrent VTE without increasing mortality and are associated with significantly lower CRNMB and composite bleeding compared with standard-dose therapy. Although major bleeding was numerically lower with reduced dosing, significance was not reached. These findings support reduced-dose DOACs as a safe and effective long-term strategy for secondary prevention of CAT. Future large-scale, prospective trials are essential to confirm these findings and to define patient-specific characteristics, such as tumor type, presence of metastatic disease, treatment regimen, thrombophilia status, renal function, and body mass index, that may guide individualized anticoagulation strategies. Additionally, more studies need to be conducted to evaluate superiority in preventing VTE recurrence among DOAC agents and optimal anticoagulation time.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
Cancer-associated thrombosis (CAT) is a major contributor to morbidity and mortality, with high rates of recurrence and clinically relevant bleeding. Extended anticoagulation reduces recurrent venous thromboembolism (VTE) by >80%, yet maintaining full-dose therapy may increase bleeding risk in cancer patients. Reduced-dose direct oral anticoagulants (DOACs) have recently been evaluated as a potential strategy to balance thrombotic and hemorrhagic risks beyond the initial 6-month treatment phase. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of reduced-dose versus standard-dose DOACs in the extended treatment of CAT.
Methods:
A systematic search of PubMed, Embase, and Scopus through June 2025 identified RCTs evaluating reduced-dose versus standard-dose regimens of apixaban rivaroxaban or edoxaban in adults with active cancer and prior VTE who had completed ≥6 months of anticoagulation. Five RCTs met eligibility criteria. Outcomes included recurrent VTE, major bleeding, clinically relevant non-major bleeding (CRNMB), composite bleeding, and all-cause mortality. Additional analyses were performed for VTE subtype and sites of bleeding. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random-effects models. Risk of bias was assessed using the Cochrane RoB 2 tool.
Results:
Five trials comprising 2,709 patients were included: 1,408 received reduced-dose DOACs and 1,301 standard-dose DOACs. We found that recurrent VTE did not differ significantly between reduced and standard-dose groups (OR 0.66, 95% CI 0.40–1.11; I²=19%). When stratified by VTE subtype, results were similar, with no significant differences for pulmonary embolism (OR 0.89, 95% CI 0.42–1.88), upper-extremity DVT (OR 0.35, 95% CI 0.04–3.33), or lower-extremity DVT (OR 1.14, 95% CI 0.48–2.71). All-cause mortality also did not differ between reduced and standard-dose therapy (OR 1.09, 95% CI 0.76–1.55; I²=39%). In terms of safety outcomes, major bleeding was less frequent with reduced-dose DOACs (OR 0.67, 95% CI 0.44–1.01; I²=0%), though not statistically significant. CRNMB was significantly reduced in the reduced-dose group (OR 0.73, 95% CI 0.56–0.95; I²=0%). Composite bleeding (major plus CRNMB) was also significantly lower (OR 0.68, 95% CI 0.54–0.85; I²=0%). Bleeding subtype analyses (gastrointestinal, genitourinary, epistaxis, intracranial) demonstrated consistently lower event rates with reduced-dose therapy, though differences were not statistically significant.
Conclusion:
In cancer patients requiring extended anticoagulation beyond six months, reduced-dose DOACs provide comparable protection against recurrent VTE without increasing mortality and are associated with significantly lower CRNMB and composite bleeding compared with standard-dose therapy. Although major bleeding was numerically lower with reduced dosing, significance was not reached. These findings support reduced-dose DOACs as a safe and effective long-term strategy for secondary prevention of CAT. Future large-scale, prospective trials are essential to confirm these findings and to define patient-specific characteristics, such as tumor type, presence of metastatic disease, treatment regimen, thrombophilia status, renal function, and body mass index, that may guide individualized anticoagulation strategies. Additionally, more studies need to be conducted to evaluate superiority in preventing VTE recurrence among DOAC agents and optimal anticoagulation time.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.