Complication comparison in intermediate-to-high risk venous thromboembolism patients, treated with high vs standard dose apixaban and rivaroxaban after low molecular weight heparin

Abstract Background In patients with intermediate-to-high risk venous thromboembolism (VTE), current guidelines recommend initial treatment with low molecular weight heparin (LMWH), followed by an oral anticoagulant. However, the studies supporting these guidelines have only focused on the use of Edoxaban and Dabigatran after 5 days of LMWH treatment. To date there are no studies supporting similarly implemented guidelines for Apixaban and Rivaroxaban. Purpose To investigate the incidence of bleeding complications and thrombosis in intermediate-to-high risk VTE patients, when treated with either lead-in high or standard dose Rivaroxaban or Apixaban, following initial LMWH treatment. Methods Through a real-life retrospective study of 844 intermediate-to-high risk VTE patients, 584 were initially treated with LMWH and subsequently Apixaban or Rivaroxaban and divided into two groups. The first group of 514 patients, received high dose Apixaban or Rivaroxaban (10mg x 2 for 7 days and 15mg x 2 for 21 days respectively) before being reduced to their standard doses. The remaining 70 patients, instead transitioned directly to the standard doses (5mg x 2 and 20mg x 1 respectively) from LMWH. All patients started treatment between 2018 and 2023, and all complications were recorded until one year following initiation of treatment. Treatment complications include recurrent VTE, separated into deep vein thrombosis and pulmonary embolism, and bleeding complications in the form of fatal, non-fatal, minor and a drop in haemoglobin. The recurrence of VTE and incidence of bleeding complications were evaluated as the primary efficacy outcome and safety outcome respectively. Results Overall, 4.7% of patients treated with initial high dose Apixaban or Rivaroxaban suffered major bleeding complications as opposed to 2.9% treated with the standard dose (p=<0.05). Out of all complications, 5 were fatal, all of which were part of the high dose group and included 3 cerebral and 2 gastrointestinal bleeds. However, minor bleeding complications were more frequent in the standard dose group, presenting in 26.1% of patients, while, paradoxically, the high dose group had similar complications in only 15.8% of patients (p=<0.05). Although treated with a higher dose, 6/478 (1,26%) incurred a recurrent thrombus within a year of treatment, while the standard dose group had no cases of recurrence, though this was not a statistically significant result. Conclusion Directly transitioning from LMWH to standard dose Apixaban/Rivaroxaban in intermediate-to-high risk VTE, leads to a statistically significant reduced incidence of major bleeding complications, without an increased risk of recurrent thrombosis.