Bleeding risk in patients with venous thromboembolic events treated with new oral anticoagulants

Niklas Wallvik,Henrik Renlund,Anders Själander

doi:10.1007/s11239-020-02319-w

Niklas Wallvik, Henrik Renlund + Show 1 more

Open Access

https://doi.org/10.1007/s11239-020-02319-w

Copy DOI

Abstract

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01–2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19–7.06) per 100 treatment years in all patients and 11.27 (CI 9.96–12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27–1.50), earlier major bleeding (HR 1.58, Cl 1.09–2.30), COPD (HR 1.28, CI 1.04–1.60) and previous stroke (HR 1.28, Cl 1.03–1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01–1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58–0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.

Highlights

The incidence of first venous thromboembolic events (VTE) in the general population is about 0.1% per year [1, 2]
Univariate Cox regression analysis indicate that female sex, hypertension, myocardial infarction, atrial fibrillation, heart failure, vascular disease, anemia, renal failure, fall tendency and cancer were associated with a higher risk of major bleeding but these risk factors were not confirmed in multivariate analysis
Significant risk factors associated with major bleeding after multivariate Cox regression analysis were age (HR 1.38, CI 1.27–1.50), previous stroke (HR 1.28, Cl 1.03–1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01–1.76), chronic obstructive pulmonary disease (COPD) (HR 1.28, CI 1.04–1.60) and 318 above 80 years

Summary

Introduction

The incidence of first VTE in the general population is about 0.1% per year [1, 2]. Total mortality associated with the diagnosis of acute pulmonary embolism is 8–17% in three months follow-up time and more than doubles after discharge from hospital [3]. In 1960, a medical breakthrough was made when vitamin K-antagonists (VKAs) was introduced as oral anticoagulant treatment of VTE [4]. A systematic review of patients with VTE on vitamin K antagonist treatment found a risk of recurrence of 3.5% (0.5% lethal) and a risk of major bleeding of 1.6–2.1% (0.2% lethal) during 3–6 months [5]. After 3 months, the risk of major bleeding is estimated to be 0.8% per patient year or 2,6 times more than without anticoagulant treatment [6].

Objectives

Methods

Results

Discussion

Conclusion