Highlights
- •Anticancer agents did not influence rates of primary outcomes during anticoagulation.
- •No interaction between apixaban and CYP3A4 or permeability glycoprotein inducers or inhibitors was found.
- •Anticancer agents can be concomitantly administered to apixaban-treated patients with venous thromboembolism.
- •An increased risk of clinically relevant non-major bleeding was observed in apixaban-treated patients with colorectal and lung cancer.
Abstract
Background
Whether concomitant administration of anticancer agents influences the efficacy and
safety of oral anticoagulants in patients treated for cancer-associated venous thromboembolism
(VTE) is undefined. The pharmacological interaction between anticancer agents and
direct oral anticoagulants is perceived as a concern.
Methods
We evaluated the effects of concomitant administration of anticancer agents on recurrent
VTE, major bleeding and death in patients with cancer-associated VTE randomised to
receive apixaban or dalteparin in the Caravaggio study.
Results
Anticancer agents were concomitantly given to 336 patients (58.3%) treated with apixaban
and to 332 patients (57.3%) treated with dalteparin. In patients treated with apixaban,
recurrent VTE occurred in 20 (6.0%) and 12 (5.0%) among patients treated or not treated
with anticancer agents, respectively (hazard ratio [HR] = 1.14; 0.55–2.38); major
bleeding occurred in 12 (3.6%) and 10 (4.2%) patients , respectively (HR = 0.79; 0.34–1.82),
and death occurred in 74 (22.0%) and 61 (25.4%) patients , respectively (HR = 0.71;
0.51–1.00). In patients treated with dalteparin, recurrent VTE occurred in 24 (7.2%)
and 22 (8.9%) among patients treated or not treated with anticancer agents, respectively
(HR = 0.71; 0.40–1.28); major bleeding occurred in 16 (4.8%) and 7 (2.8%) patients,
respectively (HR = 1.78; 0.66–4.79), and death occurred in 87 (26.2%) and 66 (26.7%)
patients, respectively (HR = 0.85; 0.62–1.18). The comparative efficacy and safety
of apixaban and dalteparin was not different in patients treated or not treated with
anticancer agents. No effect on recurrent VTE, major bleeding or death was observed
with inhibitors or inducers of P-glycoprotein and/or CYP3A4.
Conclusion
In our study, concomitant administration of anticancer agents had no effect on the
risk of VTE recurrence or major bleeding in patients treated with apixaban or dalteparin
for cancer-associated VTE.
Keywords
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Article info
Publication history
Published online: March 27, 2021
Accepted:
February 22,
2021
Received in revised form:
February 14,
2021
Received:
January 11,
2021
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
