Low-dose apixaban safe, effective as secondary prophylaxis for VTE in patients with cancer
Apixaban dose reduction to 2.5 mg twice daily appeared safe after 6 months of full-dose treatment for venous thromboembolism among patients with cancer, according to a study published in Journal of Thrombosis and Haemostasis.
Incidence rates of recurrent VTE and major bleeding both remained low after 12 months, results of the 30-month follow-up from the single-arm, interventional clinical trial showed.
“Reducing the dose of apixaban (Eliquis; Bristol Myers Squibb, Pfizer) to 2.5 mg twice daily after 6 months of 5 mg twice daily is not dangerous in [patients with cancer and VTE]. We cannot say if it is better or worse than to continue with 5 mg twice daily,” Anders Erik Astrup Dahm, MD, PhD, associate professor at Institute of Clinical Medicine at University of Oslo and senior consultant in hematology in the department of hematology at Akershus University Hospital in Norway, told Healio.
When Dahm and colleagues began planning the study in 2013, no data existed on the effect of low-dose anticoagulation as secondary prophylaxis for VTE in patients with cancer, according to Dahm. At that time, a study had just been published on patients with VTE without cancer that showed reduced-dose apixaban at 2.5 mg twice daily conferred very good protection against VTE after 6 months of full-dose treatment, without any increase in bleeding, he said.
"This dose was, and is, the dosing in the secondary prevention of cancer. So, we considered whether risk for recurrent VTE among patients with cancer would be increased to such a degree that we should keep them on 5 mg twice daily, or go for the reduced dose," he said.
The analysis included 298 patients (median age, 68.5 years; range, 19-91; 44% women) with cancer and any type of VTE. All patients received full-dose apixaban twice daily for 6 months. After 6 months, 196 patients (median age, 75 range, 19-86; 40% women) with active cancer remained on trial; researchers continued with 2.5 mg of apixaban (twice daily) for another 30 months.
Recurrent VTE, major bleeding and clinically relevant nonmajor bleeding served as key endpoints.
During the 30 months of treatment with low-dose apixaban, 14 patients experienced recurrent VTE (7.1%; 95% CI, 4-11.7), six patients experienced major bleeding (3.1%; 95% CI, 1.1-6.5), and 16 patients experienced clinically relevant nonmajor bleeding (8.1%; 95% CI, 4.7-12.8). Researchers observed the highest incidence rate of recurrent VTE during the first month of anticoagulation at the full dose (1.4%; 95% CI, 0.5-3.6), with a reduction to 0.8% (95% CI, 0.41-1.6) at 2 to 6 months with full-dose apixaban and a slight increase to 1% (95% CI, 0.5-1.9) at 7 to 12 months with low-dose apixaban. Additionally, results showed a 1.1% (95% CI, 0.6-2) incidence rate of major bleeding at 2 to 6 months and a 0.3% (95% CI, 0.1-1) rate at 7 to 12 months. Recurrent VTE and major bleeding remained low after 12 months.
“The most surprising result was the number of arterial thrombotic events — mainly strokes — that occurred during the first 6 months,” Dahm said. “We published this in our first article from the study in Thrombosis Research. I was also a little surprised by the low number of both recurrent VTE and major bleeding from 6 to 36 months.”
Dahm and colleagues concluded that reducing apixaban to 2.5 mg after 6 months of full-dose treatment demonstrated a “reasonably safe” response and effectiveness in the study cohort, with the slight increase in recurrent VTE after dose reduction outweighed by the reduction in major bleeding.
Dahm told Healio he would like to explore other ways in which the direct oral anticoagulant could help improve care.
“It would be interesting to see if one could prevent both venous and arterial thrombosis in patients with cancer by, for example, combining low-dose apixaban with a platelet inhibitor, without too many bleeding side effects,” he said.
For more information:
Anders Erik Astrup Dahm, MD, PhD, can be reached at Department of Hematology, Akershus University Hospital, Sykehusveien 25, 1478, Lørenskog, Norway; email: email@example.com.