Efficacy and Safety of Different Doses of Rivaroxaban and Risk Factors for Bleeding in Elderly Patients with Venous Thromboembolism: A Real-World, Multicenter, Observational, Cohort Study.

INTRODUCTION: Venous thromboembolism (VTE) consists of deep vein thrombosis (DVT) and pulmonary embolism (PE). Rivaroxaban is a direct oral anticoagulant (DOAC) inhibiting activated coagulation factor X (FXa), and exerts several advantages in the treatment of VTE compared to conventional therapy. However, the efficacy and safety of rivaroxaban in elderly patients with VTE was still poorly understood. METHODS: The study was carried out using an observational and non-interventional approach. A total of 576 patients aged ≥ 60 years with newly diagnosed VTE were included in the study. All patients received rivaroxaban with recommended treatment duration of ≥ 3 months for secondary prevention. In addition, 535 elderly patients with various diseases except VTE were included in the study in a retrospective and randomized way. RESULTS: The total bleeding rate was 12.2% (70/576). Major bleeding and non-major clinically relevant (NMCR) bleeding occurred in 4 (0.69%) patients and 5 (0.87%) patients, respectively. The rate of recurrent VTE was 5.4%. The mean level of D-dimers was increased by 467.2% in the elderly patients with VTE compared with the elderly patients without VTE. The elderly patients with VTE receiving rivaroxaban at a dose of 10 mg once daily (n = 134) had lower risk for bleeding (3.7% vs 14.7%; P = 0.001) and a similar rate of recurrent VTE (4.5% vs 5.7%; P = 0.596) as compared to the elderly patients with VTE receiving rivaroxaban at higher doses including 15 mg once daily and 20 mg once daily (n = 442). In addition, age, concomitant aspirin, hemoglobin, activated partial thromboplastin time (APTT), and rivaroxaban doses were independent predictive factors for bleeding events. CONCLUSIONS: The study suggested that a dose of 10 mg once daily should be the priority in elderly patients with VTE receiving long-term rivaroxaban anticoagulation therapy in view of reduced bleeding risk.

Association of CYP3A4*1B genotype with Cyclosporin A pharmacokinetics in renal transplant recipients: A meta-analysis.

OBJECTIVE: Cyclosporine (CsA) is a substrate of cytochrome P450 (CYP) 3A4 with a narrow therapeutic index and large individual difference. CYP3A4*1B is reported to be associated with CsA pharmacokinetics parameters, but the relevance is still in dispute. Therefore, a meta-analysis was employed to evaluate the influence of CYP3A4*1B on CsA pharmacokinetics at different post-transplantation times in adult renal transplant recipients. METHODS: Studies on evaluating the CYP3A4*1B genotype and CsA pharmacokinetics were retrieved through a systematical search of relevant database including PubMed, Emabase, Web of science, the Cochrane Library, Clinical Trials.gov and three Chinese literature databases (up to 15 October 2017). The pharmacokinetic parameters: weight-adjusted CsA daily dose (Dose), cyclosporine trough concentration (C0) and trough concentration/weight-adjusted CsA daily dose ratio (C0/Dose ratio) were extracted, and all statistical analysis were performed by using Review Manager 5.1.0. RESULTS: Four studies (involving 452 adult renal transplant recipients) were included in this meta-analysis. For the C0/Dose ratio, in all included renal transplant recipients, CYP3A4*1B carriers exhibited higher C0/Dose ratio than CYP3A4*1 (WMD 7.38, 95% CI 1.26-13.51; P = 0.02). The differences between CYP3A4*1B carriers and CYP3A4*1 in Dose (WMD 0.36, 95% CI 0.85-0.12; P = 0.14), C0 (WMD 10.81, 95% CI 77.72-99.34; P = 0.81) were not statistically significant. According to post-transplantation time, subgroup analysis also showed no significant statistical significance between CYP3A4*1B carriers and CYP3A4*1 carriers in Dose or C0. However, this result should be further explored because only four studies were included. CONCLUSIONS: CYP3A4*1B is associated with CsA C0/Dose ratio in renal transplant recipients which indicates patients with CYP3A4*1B allele require lower dose of CsA to reach target blood concentration compared with the CYP3A4*1 carriers.