Abstract
Introduction Clinical practice guidelines on cancer-associated thrombosis (CAT) recommend extended duration anticoagulation beyond 6 months in patients with active cancer/ongoing treatment. However, data on reduced dose anticoagulation to prevent recurrent VTE in this group are only now emerging. This retrospective, single-centre observational study reports on the efficacy and safety of extended duration therapy with reduced dose anticoagulation in a large real-world cohort of patients with cancer and VTE. Methods Consecutive patients with ongoing review in a dedicated CAT clinic at a large, tertiary centre from January 2017 were included. Inclusion criteria were patients with active cancer and VTE, who were switched to a prophylactic dose of anticoagulation at the discretion of their treating physician after completing at least 6 months of full-dose anticoagulation. Prophylactic dose of anticoagulation was defined as apixaban 2.5mg BD, rivaroxaban 10mg OD or enoxaparin 40mg OD (20mg OD for weight <50kg). Patients on reduced dose therapeutic anticoagulation due to low weight/impaired renal function, or whose index thrombotic events were tumour thrombus, central venous catheter (CVC)-associated DVT, and superficial venous thrombosis were excluded. Recurrent VTE, bleeding events and mortality in the 12-month period after anticoagulant dose reduction were collected. Data were pulled from electronic health records and manually curated. Recurrent VTE was defined as all imaging-proven PE or DVT occurring during the 12-month study period. On-treatment recurrent VTE excluded events occurring in the absence of anticoagulation or if anticoagulation had been held for >48hours. Major bleeding and clinically relevant non-major bleeding were defined as per ISTH criteria. Results A total of 299 patients were included in the cohort with anticoagulant dose reduction occurring at median 6.2 months (IQR 6-7.5) from time of index VTE. The average age was 63y (IQR 53-72), 56% were female. The commonest cancer types were gynaecological (27.1%) & haematological (17.7%). The index VTE was PE +/- DVT in 63.2%; isolated DVT in 30.4% and unusual site thrombosis in 6.4%. Apixaban was the commonest choice of low dose anticoagulant for secondary thromboprophylaxis after at least 6 months of therapeutic anticoagulation (66.6%), followed by rivaroxaban (28.8%) and enoxaparin (4.7%). Recurrent VTE occurred in 12/299 (4%) patients; 83.3% were symptomatic VTE. 5/12 (41.7%) had isolated DVT; 16.7% PE +/-DVT; 33.3% CVC thrombosis; 8.3% unusual site. 33.3% recurrent VTE occurred in the first 3 months of anticoagulant stepdown; 50% at 3-6 months and 16.7% at 6-12 months. 75% patients with recurrence were prescribed apixaban, 16.7% rivaroxaban and 8.3% enoxaparin. On-treatment recurrent VTE occurred in 9/299 (3%) patients; 77.8% were symptomatic. 4/9 (44.4%) had isolated DVT; 22.2% PE +/-DVT; 22.2% CVC thrombosis; 11.1% unusual site. 44.4% on-treatment recurrent VTE occurred in the first 3 months of anticoagulant stepdown; 44.4% at 3-6 months, and 11.1% at 6-12 months. 77.8% patients were on apixaban, 11.1% on rivaroxaban and 11.1% enoxaparin. 4/299 (1.2%) patients had major bleeding and 10/299 (3.3%) had clinically relevant non-major bleeding. All-cause mortality was 26% over the 12-month study period.
Conclusion Our study shows rates of recurrent VTE remain reassuringly low in a large real-world cohort when reduced dose anticoagulation is used for secondary prophylaxis after the initial 6-month treatment period. The VTE recurrence rate in our cohort over a 12-month period was slightly higher than seen in the recent API-CAT study, an RCT which showed that extended anticoagulation with low-dose apixaban was non-inferior to full-dose for prevention of recurrent CAT (Mahé et al 2025). However, our cohort likely had poorer performance status/more advanced disease than the API-CAT cohort, based on the higher all-cause mortality. Rates of all types of bleeding were low, although the nature of retrospective data collection likely led to an underestimation of these figures. Low dose anticoagulation is used in clinical practice for secondary thromboprophylaxis in patients with CAT without a signal for increased VTE recurrence and with low bleeding complications. Further data are required on the longer-term continuation of this thromboprophylactic strategy in an era when patients are living longer with advanced cancer.
