Self-assembly processes of three octahedron-shaped [Pd6L12]12+ cages were investigated by an NMR-based quantitative approach (QASAP).

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.

What is known and objective Edoxaban has three dose adjustment factors (creatinine clearance, 15‐50 mL/min; body weight, 60 kg or less; and concomitant medication with potent P‐glycoprotein inhibitors) to prevent bleeding that results from elevated blood concentrations of the drug. A dose reduction (from 60 to 30 mg/day of edoxaban) is recommended for patients with even one of those. However, it is not clear whether 30 mg/day of edoxaban is adequate for patients with multiple dose adjustment factors. We thus investigated the association between the number of the dose adjustment factors and bleeding risk in patients receiving edoxaban. Methods We retrospectively analysed 198 patients who received 30 mg/day of edoxaban between April 2015 and March 2017 with follow‐up for 1 year. Results The incidences of major bleeding were 1.4%, 7.3% and 20.0% in patients with 0‐1, 2 and 3 dose adjustment factors, respectively. The Cox proportional hazards regression model revealed that the risk of major bleeding was higher in patients with 2 (hazard ratio [HR]: 5.80, 95% confidence interval [CI]: 0.96‐44.05, P = .055) or 3 (HR: 17.70, 95% CI: 2.12‐147.70, P = .012) dose adjustment factors than in those with 0‐1 dose adjustment factor. What is new and conclusion This is the first study to evaluate the risk of bleeding in patients administered 30 mg/day of edoxaban based on the number of dose adjustment factors in clinical practice. For patients receiving edoxaban, as the number of the dose adjustment factors increases, the risk of major bleeding is elevated. In patients with multiple dose adjustment factors, not only one level of dose reduction, but further dose reductions may be considered. Further studies with a larger sample size are needed to confirm these findings.