Low dose apixaban as secondary prophylaxis of venous thromboembolism in cancer patients – 30 months follow‐up

Abstract

Background There are no data on the effect of low‐dose anticoagulation as secondary prophylaxis for venous thromboembolism (VTE) in cancer patients. We assessed the efficacy and safety of low‐dose apixaban for 30 months, after initial 6 months of full‐dose treatment. Methods We included 298 patients with cancer and any type of VTE in a single arm interventional clinical trial. All patients were treated with full‐dose apixaban (5 mg twice daily) for 6 months. Total 196 patients with active cancer after 6 months treatment continued with apixaban 2.5 mg twice daily for another 30 months. The main endpoints were recurrent VTE, major bleeding and clinically relevant non‐major bleeding. Results During the 30 months of treatment with low‐dose apixaban 14 (7.6%; 95% confidence interval (CI) 4.0%–11.7%) patients experienced recurrent VTE, six (3.1%; 95% CI 1.1%–6.5%) experienced major bleeding and 16 (8.1%, 95% CI: 4.7%–12.8%) experienced clinically relevant non‐major bleeding. The incidence rate per person month of recurrent VTE was 0.8% (95% CI 0.41–1.6) at 2–6 months with full‐dose apixaban, and 1.0% (95% CI 0.5–1.9) at 7–12 months with low‐dose apixaban. The incidence rate of major bleeding was 1.1% (95% CI 0.6–2.0) at 2–6 months, and 0.3% (95% CI 0.1–1.0) at 7–12 months. Between 12 and 36 months the incidence rate of recurrent VTE and major bleedings remained low. Conclusion Dose reduction of apixaban to 2.5 mg twice daily seems safe after 6 months of full‐dose treatment. After 12 months the incidence rate of recurrent VTE and major bleeding remained low.

“Low dose apixaban as secondary prophylaxis of venous thromboembolism in cancer patients ‐ 30 months follow‐up”: Reply

“…We have taken a closer look at the patients with malignant hematological diseases in our recently published study on low-dose apixaban as secondary prophylaxis for venous thromboembolism (VTE). 2 In our cohort of hematological patients (see Table 1), 3/4 recurrent VTE were in patients receiving low-dose apixaban, 2/4 in multiple myeloma. As for bleeding, three of a total of 29 patients experienced major bleed, all on full-dose treatment, one in eight patients with multiple myeloma experienced a major bleed on full-dose.…”

A Review of the Past, Present and Future of Cancer-associated Thrombosis Management

“…A multicentre, single-arm trial in Norway assessed recurrent VTE, major bleeding and CRNMB in patients treated for 6 months with apixaban 5 mg twice daily followed by 2.5 mg twice daily for an additional 30 months. 56 The groups were similar in proportions of gender, metastatic disease and cancer types, but the low-dose cohort was slightly older. Patients receiving full-dose apixaban during the first 6 months had a 4% (95% CI 2.1-6.9) recurrent VTE rate compared with 7.1% (95% CI 4.0-11.7) in the low-dose extended treatment group, which mostly occurred in months 7-12.…”

Unanswered questions in cancer‐associated thrombosis

“…Lastly, ideal dosing of anticoagulation beyond the initial six months remains an unanswered question, with currently available data arising from studies mostly using therapeutic doses. While reduced doses might be appropriate for some patients without cancer, evidence demonstrating efficacy and safety is limited in patients with active cancer 69 . Whether an improved risk/benefit ratio can be achieved with lower doses of DOACs is being addressed in ongoing RCTs (APICAT trial, http://clinicaltrials.gov NCT03692065, EVE trial, http://clinicaltrials.gov NCT03080883).…”