Safety profile of rivaroxaban in first-time users treated for venous thromboembolism (deep vein thrombosis and pulmonary embolism) in four European countries

Background: The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and secondary prevention of venous thromboembolism in routine clinical practice. Methods: Cohorts were created using healthcare databases from the UK, the Netherlands, Germany and Sweden. Patients given a first prescription of rivaroxaban or vitamin K antagonist during the period from December 2011 (in the UK, January 2012) to December 2017 (in Germany, December 2016) for venous thromboembolism indication, with no record of atrial fibrillation or recent cancer history, were observed until the occurrence of each safety outcome that led to hospitalization (intracranial, gastrointestinal, urogenital or other bleeding), or death or until study end (December 2018; in Germany, December 2017). Crude incidence rates of each outcome per 100 person-years were computed, and adjusted odds ratios for risk factors were generated from nested case-control analyses. Results: Overall, 44 737 rivaroxaban and 45 842 vitamin K antagonist patients were enrolled. Incidence rates were similar between rivaroxaban and vitamin K antagonist users with some exceptions, including higher numerical incidence rates for gastrointestinal bleeding in rivaroxaban users than for vitamin K antagonist users. Rivaroxaban and vitamin K antagonist use was associated with increased bleeding risk compared with non-use. Gastrointestinal bleeding exhibited the most consistent odds ratios (95% confidence interval) across countries, ranging from 2.24 (1.79–2.82) to 4.10 (1.90–8.87) and from 2.24 (1.76–2.84) to 6.76 (2.20–20.80) for rivaroxaban use and vitamin K antagonist use, respectively. Bleeding risks decreased with increasing treatment duration. Among rivaroxaban users, mortality and bleeding risk generally increased with age, renal impairment and diabetes. Conclusions: These data broadly support safety findings from randomized clinical trials; no unexpected safety concerns related to bleeding risks were found.