The research, which combined the results of three randomised trials, encourages clinicians to consider reducing doses in certain patients.
A recent systematic review and meta-analysis suggest reduced-dose direct oral anticoagulants have better safety and similar efficacy to full-dose approaches.
Managing the possibility of venous thromboembolisms in cancer patients can be a fine line to walk. Too little anticoagulant treatment and you run the risk of blood clots, while too much treatment can lead to bleeding events.
Direct oral anticoagulants have become a popular choice for long-term VTE management, but the safety and efficacy of reduced-dose DOACs compared to full-dose DOACs is somewhat unclear.
Now, a new systematic review and meta-analysis, published in the American Journal of Hematology, has pooled safety and efficacy data comparing reduced- and full-dose DOAC use for VTE prophylaxis in cancer patients to provide clarity on the matter. Its findings suggest that reduced-dose DOACs provide similar efficacy to full-dose DOACs – while also potentially reducing the risk of clinically-relevant bleeding – in cancer patients.
“Cancer patients inherently carry a higher anticoagulant-related bleeding risk due to tumour invasion, abnormal angiogenesis, and treatment-related factors such as thrombocytopenia, surgery, and type of systemic therapy,” the researchers wrote.
“Additionally, anticoagulant-related bleeding in patients with cancer is a significant cause of both morbidity and mortality. Given these concerns, strategies that can effectively reduce bleeding risk, such as the use of reduced-dose apoxiban or rivaroxaban regimens, represent a valuable clinical option.”
The research team identified 2178 adult cancer patients from three randomised clinical trials that compared reduced- and full-dose DOACs used for extended secondary anticoagulant prophylaxis purposes (i.e., used more at least six months).
The patients in two of the three trials were predominantly female (57% and 55% versus 45%) and had metastatic disease (66% and 60% across the two studies where this variable was reported). The mean age of patients included in each of the three trials ranged from 58 to 67 years.
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There was no difference in the study’s primary outcome – the risk of recurrent VTE – between the reduced- and full-dose groups (pooled risk ratio and 95% confidence interval 0.87 [0.10-7.83]). There was also no difference in the risk of clinically relevant bleeding, a composite measure that included both major and clinically relevant non-major bleeding events (0.77 [0.55-1.06]).
A subgroup analysis of the two trials that defined “active” cancer in their inclusion criteria again found no difference between treatment approaches when considering the risk of recurrent VTE (0.87 [0.10-7.83]), but found a reduced risk of the composite measure of clinically relevant bleeding in the reduced-dose group compared to the full-dose group (0.77 [0.60-0.99]).
There was no difference between treatments when major bleeding and clinically relevant non-major bleeding were considered separately.
“Although the absolute benefit may vary across cancer patient subgroups, this modest reduction in bleeding risk may be clinically meaningful in select high-risk individuals, particularly considering the absence of significant differences in recurrent VTE rates between the dosing strategies,” the researchers noted.
“Clinicians should carefully consider this strategy, weighing individual patient bleeding risks and VTE recurrence probabilities.”
