Risk Factors for Major Bleeding and Clinically Relevant Non-major Bleeding in Japanese Patients Treated with Edoxaban

Abstract

Edoxaban is used to prevent and treat stroke or systemic embolism such as venous thromboembolism. Although bleeding is the most common complication of anticoagulants, only a few studies have addressed the safety of direct oral anticoagulants in East Asian patients. In this study, we investigated the risk factors for bleeding in Japanese patients receiving edoxaban. A retrospective review of the records of 198 patients who received 30 mg/d edoxaban in our hospital between April 2015 and March 2017 was performed. Subsequently, these patients were followed up to 1 year. Seven (3.5%) and 22 (11.1%) patients developed major bleeding and clinically relevant bleeding, respectively. In the univariate Cox regression analyses, low baseline hemoglobin levels (p 0.002) and low baseline creatinine clearance (p 0.020) were significantly associated with major bleeding. Multivariate Cox regression analysis revealed that a low baseline hemoglobin level was a significant risk factor for major bleeding and clinically relevant bleeding [hazard ratio 1.67 per 1 g/dL decrease (95% confidence interval 1.14-2.56, p 0.008) and hazard ratio 1.31 per 1 g/dL decrease (95% confidence interval 1.06-1.62, p 0.013), respectively]. Baseline hemoglobin level in quartiles also showed a quartile-dependent decrease in major bleeding and clinically relevant bleeding event. These results suggest that low baseline hemoglobin level is a significant risk factor for both major bleeding and clinically relevant bleeding in Japanese patients receiving edoxaban. Thus, these patients should be carefully monitored.

Clinical Features and Follow-up Outcomes of Individualized Low-dose DOAC Therapy in Chinese Patients Aged 60 Years and Older: A Single-center Study

“…Studies have shown that DOAC dose can be reduced in patients with the following clinical characteristics: elderly (≥ 75 years old), female, low weight (≤ 60kg), renal insu ciency (CrCl ≤ 50ml/min), previous bleeding history, combined history of hypertension, combined use of dronedarone or antiplatelet drugs, etc. [11] Studies have shown that Asian patients with low body weight, cancer, low baseline hemoglobin levels, prolonged prothrombin time, and low creatinine clearance are at increased risk of edoxaban related bleeding [12][13][14] . This study found that the clinical characteristics of patients taking low-dose DOAC regimen included: age ≥ 80 years old, weight ≤ 60kg, ADL score ≤ 60 points, HAS-BLED score ≥ 3.0 points, eGFR < 60ml/min/1.73m², and baseline hemoglobin < 120g/L.…”

The importance of renal function in anemic patients treated with edoxaban after orthopedic surgery in a real-world clinical setting: A retrospective study

“…A lower baseline Hgb level was also a significant risk factor for bleeding in Japanese patients receiving Edx. [ 21 ] The implications of this association between the baseline Hgb levels and renal function for Edx treatment are interesting and should be investigated further.…”

Delayed lumbar plexus palsy due to giant psoas hematoma associated with vertebral compression fracture and direct oral anticoagulants: a case report

“…The frequency of major or clinically relevant nonmajor bleeding events related to edoxaban was reported to range from 3.8 to 19.2% [ 15 – 19 ]. Studies indicated that the risk factors of DOAC-related bleeding events include heavy alcohol use, uncontrolled hypertension, increasing age, heart failure, vascular disease, antiplatelet use, chronic renal failure, and diabetes mellitus [ 17 , 20 ]. In our case, the patient’s age and comorbidities, including excess alcohol use, carotid artery stenosis, arteriosclerosis obliterans, and diabetes mellitus, possibly increased the risk of DOAC-related hematoma.…”