During the 66th American Society of Hematology Annual Meeting and Exposition, Jordan K. Schaefer, MD, MSc, of the University of Michigan in Ann Arbor, presented findings that support the 2021 American College of Chest Physician Guidelines for reduced-dose apixaban or rivaroxaban in secondary prevention of venous thromboembolism (VTE). The registry-based cohort study showed reduced direct oral anticoagulant (DOAC) dosing was associated with a decreased bleeding rate and lower health care utilization compared with prophylactic dosing in a real-world cohort of patients with VTE.
The study included 851 matched patients drawn from the Michigan Anticoagulation Quality Improvement Initiative with a minimum of six months of anticoagulation and nine months of follow-up. Patients were matched based on their propensity scores and factors anticipated to influence anticoagulant treatment including demographics, characteristics of the initial clotting events, comorbidities, medication use, length of follow-up, and baseline hemoglobin and platelet value.
Average follow-up was 21.1 months, and the primary outcome was recurrent VTE. Secondary outcomes included new cases of any thrombosis, including pulmonary embolism (PE) and deep vein thrombosis (DVT), bleeding, visits to emergency departments, hospital stays, and death. Researchers aimed to examine how dose reduction is being implemented in a real-world setting for extended-phase treatment of VTE and if it has any effect on clinical outcomes.
Overall, patients on therapeutic dose (n=662) compared with patients on prophylactic dose (n=189) had similar outcomes of PE (1.8 vs. 0.3 PE/100 patient years; p=0.21), DVT (1.1 vs. 0.3 DVTs/100 patient years; p=0.22), and thrombosis rates (4.1 vs. 1.3 events/100 patient years; p=0.055). Additionally, no significant difference was observed in major bleeding rate (p=0.067) or mortality between the two groups.
“While studies have shown that rates of recurrent VTE were similar with dose reduction, they haven’t definitively established bleeding reduction benefit from dose reduction,” Dr. Schaefer told ASH Clinical News. However, the study showed that therapeutic anticoagulation resulted in a higher bleeding event rate (45.6 vs. 40.0 events; p=0.039), more bleed- or thrombosis-related emergency department visits (17.2 vs. 9.1; p=0.002), and more hospitalizations (9.0 vs. 5.1; p=0.011) than prophylactic dosing.
“The studies on which the guidelines are based had specific criteria for eligibility, and we weren’t sure if people were applying those study findings to patients with a higher clotting risk,” Dr. Schaefer said. After propensity matching, “the only real difference we’re seeing still is bleeding and health care utilization, which raises the question of whether dose reduction is beneficial for at least some of the patients in our real-world study population.”
Dr. Schaefer cited the potential for selection bias as a limitation that could lead to healthier patients receiving dose reductions, resulting in better outcomes. He and his team “recommend larger observational studies and randomized trials to confirm the potential benefits for dose reduction, especially in patients who are at a higher clotting risk, for example, patients with active cancer.”
“DOACs are potentially life-saving drugs, but they increase the risk of bleeding. It’s important to be familiar with randomized control trials — including their eligibility criteria — to see if those findings can be applied to your particular patient. Also, it’s important to individualize the care plan and engage in shared decision-making when it’s not clear when dose reduction is appropriate,” Dr. Schaefer said. “Caution is needed. We still don’t have enough information about patients with a higher clotting risk or patients within certain subgroups.”
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Schaefer J, Errickson J, Kong X, et al. Treatment versus prophylactic apixaban or rivaroxaban for extended venous thromboembolic disease management. Abstract 699. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 8, 2024; San Diego, California.
