Vol.:(0123456789) 1 3 Journal of Thrombosis and Thrombolysis https://doi.org/10.1007/s11239-020-02317-y Thromboprophylaxis for patients with newly diagnosed vs. recurrent cancers: a post‑hoc analysis of the avert trial James Zhang 1,2  · Marina Atalla 2  · Ranjeeta Mallick 3  · Philip S. Wells 2  · Marc Carrier 2 Accepted: 12 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract Venous thromboembolic disease (VTE) is a common complication among patients with cancer. Data reporting risk of VTE among patients receiving chemotherapy for recurrent cancer compared to those with newly diagnosed tumors is scarce. Furthermore, it is unclear if thromboprophylaxis is benefcial and safe in these specifc patient populations. Post-hoc analy- sis of the AVERT trial which was a randomized, placebo-controlled, double-blind trial comparing apixaban therapy to placebo for VTE prophylaxis among cancer patients who were intermediate-to-high risk for VTE and who were initiating chemotherapy. The HRs for recurrent VTE and major bleeding episodes in patients with newly diagnosed and recurrent cancers were calculated using a Cox regression model controlling for age, gender, and center. Of the 563 included patients 469 and 93 patients had newly diagnosed and recurrent cancers, respectively. Patients with recurrent cancer have a higher risk of VTE (Hazard ratio (HR): 1.53 (95% CI 1.0 to 2.33; p = 0.047) and major bleeding episodes (HR 2.89 (95% CI 1.52 to 5.49; p = 0.001) compared to those with newly diagnosed cancer. In patients with newly diagnosed cancers, the use of apixaban was associated with a signifcantly lower risk of VTE (HR 0.45; 95% CI 0.27–0.76; p = 0.002) and a higher rate of major bleeding (HR 2.10; 95% CI 1.09–4.08; p = 0.028). In patients with recurrent cancer, apixaban was associated with a signifcant lower rate of VTE (HR 0.26; 95% CI 0.13–0.53; p < 0.001) without an associated signifcantly increased risk of major bleeding (HR 1.82; 95% CI 0.36–9.15; p = 0.466). Patients with recurrent cancer seem to be at higher risk of recurrent VTE and major bleeding complications compared to those with newly diagnosed tumors. Apixaban appears to be safe and efective in these patient populations. Keywords Venous thrombosis · Venous thromboembolism · Hemorrhage · Neoplasms · Apixaban Highlights • Patients with recurrent cancer are at high risk of venous thromboembolism (VTE). • Thromboprophylaxis with apixaban is safe and efective for the prevention VTE in patients initiating chemother- apy. • Apixaban may signifcantly decrease the risk of VTE without increasing the risk of bleeding among patients with recurrent cancer initiating chemotherapy. Introduction Venous thromboembolic disease (VTE) is a common com- plication among patients with cancer and is associated with signifcant morbidity and mortality [1–4]. This association is thought to be due to various factors such as a hypercoagulable state via the production of procoagulant substances, increased infammation from the tumor, and anatomical compression that can occur with certain tumor locations [5, 6]. These molecular and physiological mechanisms promoting throm- bus generation vary with tumor type as well as disease stage. A population-based cohort study reported a VTE incidence rate of 27.7 (95% confdence interval [CI] 24.0 to 32.0) for * Marc Carrier mcarrier@toh.ca 1 Institut du Savoir Montfort, Montfort Hospital, Ottawa, Canada 2 Department of Medicine, University of Ottawa, the Ottawa Hospital Research Institute, 501 Smyth Road, Box 201 a, Ottawa, ON K1H 8L6, Canada 3 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada