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

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.

Safety of Non-Vitamin K Antagonist Oral Anticoagulant Treatment in Patients with Chronic Kidney Disease and Kidney Transplant Recipients

“…Among the 18,219 patients, 938 had a major bleeding and the rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years. Renal failure was associated with a higher risk of major bleeding in this study, but the finding was not confirmed in multivariate analysis [46]. Another study, conducted by Bixby,Shaikh et al,compared 197 adult KTRs who received either warfarin or NOACs due to VTE or AF.…”

Safety profile of rivaroxaban in first-time users treated for venous thromboembolism in four European countries

“…Consistent with known risk factors and clinical trials [ 3 , 9 ], our data showed that IRs of intracranial, gastrointestinal and other bleeding events were higher in patients aged 75 years or older. Older age was also found to be an independent risk factor for major bleeding in a study of Swedish national registries (normalized hazard ratio [95% CI]: 1.38 [1.27–1.50]) [ 28 ].…”

The Risk of Major Bleeding With Apixaban Administration in Patients With Acute Kidney Injury

“…In addition, other risk factors for bleeding were collected including drug interactions increasing apixaban exposure/area under the curve (amiodarone, diltiazem, verapamil, cyclosporine, azole antifungals, dronedarone, clarithromycin, erythromycin), alcohol use, thrombocytopenia (<150/µL), increased bilirubin (>1.2 mg/dL) or liver function tests (>3 times upper limit of normal), uncontrolled blood pressure (>160 mmHg systolic blood pressure), active cancer undergoing treatment, history of cirrhosis, ischemic stroke, chronic obstructive pulmonary disease (COPD), peptic ulcer bleeding (PUD), or prior bleeding event. 17,18 Baseline serum creatinine was defined as the most recent documented lab value in the chart within the prior year or as documented by physician progress notes, and the cause of AKI was also determined by physician documentation. Patients were followed from the time of admission through hospital discharge for outcome evaluation.…”