Q&A: Lower blood thinner dose can reduce bleeding risk
Key takeaways:
- Reduced dosing of direct oral anticoagulants for VTE conferred comparable efficacy as full dosing.
- Reduced dosing appeared linked to lower bleeding risk and fewer ED visits.
Reduced dosing of direct oral anticoagulants may offer comparable efficacy as full dosing for adults with venous thromboembolism history while decreasing bleeding risk and reducing health care utilization, according to study results.
Researchers at Michigan Medicine conducted a registry-based cohort study of 978 adults undergoing direct oral anticoagulant (DOAC) therapy for blood clots to evaluate whether clinical outcomes differed between those who had doses reduced after initially receiving full therapeutic dosing and those who continued to receive full therapeutic doses.
Patients included in analysis underwent anticoagulation for deep vein thrombosis and/or pulmonary embolism between 2012 and 2023. Overall, 18.8% had provoked VTE, 32.4% had cancer or a history of cancer and 7.9% were undergoing or had received chemotherapy.
Patients received apixaban (Eliquis; Bristol Myers Squibb, Pfizer) or rivaroxaban (Xarelto, Janssen Pharmaceuticals). All patients had minimum follow-up of 9 months.
Researchers used propensity matching to compare outcomes between 662 patients who received the full therapeutic dose and 189 patients who received prophylactic dosing.
Results — presented at ASH Annual Meeting & Exposition in December — showed similar rates of recurrent VTE (PE, 1.8 vs. 0.3 per 100 patient-years; DVT, 1.1 vs. 0.3 per 100 patient-years) and any thrombosis (4.1 events vs. 1.3 events per 100 patient-years) between the therapeutic dose and prophylactic dose groups.
Patients who received the prophylactic dose had a lower rate of bleeding events (40 vs. 45.6 per 100 patient-years; P = .039) as those who received the full therapeutic dose, with no statistically significant difference in rate of major bleeding events (1.8 vs. 3.6 per 100 patient-years).
Patients who received therapeutic anticoagulation also had more bleed- or thrombosis-associated visits to the ED (17.2 vs. 9.1 per 100 patient years; P = .002) and hospitalizations (9 vs. 5.1 per 100 patient-years; P = .011).
Researchers reported comparable mortality rates between groups.
The findings support a 2021 guideline from American College of Chest Physicians that recommended reduced-dose rivaroxaban or apixaban for extended-phase VTE management, Jordan K. Schaefer, MD, MSc, associate professor in the division of hematology/oncology at University of Michigan, and colleagues concluded.
“These results are potentially practice changing, but it’s important that physicians understand which patients are appropriate to offer dose reduction,” Schaefer told Healio.
“Additionally, with all anticoagulation decisions, it is important to engage patients in shared decision-making, where you discuss the known pros and cons of reducing the dose of anticoagulant drugs,” Schaefer added. “We want to help patients make a decision that is appropriate for their particular circumstances.”
Healio spoke with Schaefer about why this study is important, the implications of the findings and the next steps in research.
Healio: What risks are associated with anticoagulation for VTE management?
Schaefer: There is a risk for bleeding associated with all anticoagulant drugs, including direct oral anticoagulants. Bleeding is the most serious risk we worry about. That’s one reason why there has been an interest in studies like these. We want to do anything we can to mitigate or reduce that risk.
Healio: What motivated you to conduct this study?
Schaefer: There were some large, well-done randomized controlled trials done on this topic a while ago. After patients completed 6 months of anticoagulation, these studies showed that the clotting outcomes with the reduced dose seemed to be similar to the full dose. However, they didn’t definitively show that the bleeding outcomes improved with the reduced dose. Also, previous studies had evaluated lower thrombotic risk patients. For patients in these studies, there was clinical equipoise or uncertainty as to whether they needed to continue on an anticoagulant to begin with. In practice, however, we have seen people applying these study results even to very high-risk patients who definitely needed to be on an anticoagulant drug. So, our first goal was to see how this information was being applied to routine, real-world practice. The second was to see whether there was any benefit to reducing anticoagulant dose in terms of avoiding bleeding.
Healio: How did you conduct this study and what did you find?
Schaefer: We worked with the Michigan Anticoagulation Quality Improvement Initiative, which is a collaborative of clinics in the state. We identified patients who were on apixaban or rivaroxaban for the indication of VTE. Then we did propensity matching to compare two similar groups of patients in terms of age, health histories, and risk factors for bleeding and clotting. We compared patients who stayed on full dosing of anticoagulation to patients who reduced their dose of anticoagulation.
Our study showed similar clotting outcomes for patients who stayed on full-dose blood thinners or anticoagulants and those whose doses were reduced. There was slightly less bleeding among patients on the reduced dose of anticoagulation compared with the patients who stayed on the full dose. We also saw reduced emergency room visits and hospitalizations among patients on the reduced dose.
Healio: What is the potential impact of these results?
Schaefer: There is still a need for more randomized studies to confirm these findings, but this study did influence my own practice. Since conducting this study, I’ve been more likely to consider offering dose reduction to appropriate patients. I had been reluctant before. So, yes, the results are potentially practice changing, but it’s important that doctors understand the randomized trials that were done and which patients are appropriate candidates for dose reduction.
Healio: What is next in your research on this?
Schaefer: At least two other groups have been looking at the same question. We are hoping to combine the information from these other centers and create a larger study with more patients.
Reference:
- Schaefer JK, et al. Abstract 669. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.
For more information:
Jordan Schaefer, MD, MSc, can be reached at jschaef@med.umich.edu.
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