Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non‐valvular atrial fibrillation from the RE‐LY trial

Summary. Background: Dabigatran etexilate (DE) is an orally absorbed prodrug of dabigatran, a thrombin inhibitor that exerts potent anticoagulant and antithrombotic activity. Objectives: To characterize the pharmacokinetics of dabigatran in patients with non‐valvular atrial fibrillation (AF) from the Randomized Evaluation of Long‐term Anticoagulant Therapy (RE‐LY) trial and to quantify the effect of selected factors on pharmacokinetic (PK) model parameters. Patients and methods: A total of 27 706 dabigatran plasma concentrations from 9522 patients who received DE 110 or 150 mg twice daily were analyzed with non‐linear mixed‐effects modeling. Results: The pharmacokinetics of dabigatran were best described by a two‐compartment disposition model with first‐order absorption. The covariates creatinine clearance (CRCL), age, sex, heart failure and the ethnic subgroup ‘South Asian’ exhibited statistically significant effects on apparent clearance of dabigatran. Body weight and hemoglobin significantly influenced the apparent volume of distribution of the central compartment. Concomitant medication with proton‐pump inhibitors, amiodarone and verapamil significantly affected the bioavailability. However, all of the statistically significant factors that were identified, except for renal function status, showed only small to moderate effects (< 26% change in exposure at steady state). On the basis of simulations from the final population PK model, a dose of 75 mg twice daily would result in similar exposure for severely renally impaired patients with CRCL of 15–30 mL min^?1 and patients with normal renal function receiving 150 mg twice daily. Conclusions: The analysis provides a thorough PK characterization of dabigatran in the AF patient population from RE‐LY. None of the covariates investigated, with the exception of renal function, warrants dose adjustment.     

达比加群酯在非瓣膜性房颤患者抗凝治疗中的应用效果

目的 探讨达比加群酯在非瓣膜性房颤患者抗凝治疗中的应用效果.方法 选取2017年5月至2019年6月入我院治疗的120例非瓣膜性房颤患者,采用信封法将其分为对照组和研究组,每组60例.对照组给予华法林治疗,研究组给予达比加群酯治疗.比较两组的凝血指标、肝肾功能指标、出血事件、栓塞事件及不良反应发生情况.结果 治疗后,研...     

华法令对心房颤动患者的抗凝效果与安全性研究

目的　评价华法令用于心房颤动患者抗凝治疗的效果与安全性。方法　选择符合研究标准的 2 2 3例心房颤动患者 ,随机分为华法令治疗组 112例与阿司匹林对照组 111例。治疗组给于华法令片 ,每次 2 .5mg ,第 1天每天 3次 ,第 2天每天 2次 ,然后每天 1次 ,治疗开始每两天复查 1次国际标准化比值 (INR)。稳定后每月复查 1次INR ,依据INR调整华法令用量 ,使INR保持在 2 .0～ 3.0之间。对照组给予阿司匹林 5 0mg ,每天 3次 .。每两周进行1次随访 ,随访期为 1年 ,观察血栓栓塞事件及有无出血情况。结果　华法令组的栓塞发生率为 1.8% ,阿司匹林组为4 .5 8% ,两组比较差异具有统计学意义 (P <0 .0 5 ) ,华法令组出血发生率为 3.6 % ,阿司匹林组为 1.83% ,两组比较差异无统计学意义 (P >0 .0 5 )。结论　心房颤动的患者使用华法令抗凝治疗 ,使INR保持在 2 .0～ 3.0之间 ,能有效的预防血栓栓塞事件的发生 ,不良反应轻微 ,临床用药安全。     

Personalizing oral anticoagulant treatment in patients with atrial fibrillation

For decades, warfarin has remained the standard oral anticoagulation for stroke prevention in atrial fibrillation (AF). Three novel oral anticoagulants (NOACs) have been recently approved for stroke prevention in non-valvular AF: dabigatran, rivaroxaban and apixaban. Better pharmacological and clinical profiles make these newcomers a preferable alternative over warfarin. Current AF guidelines do not endorse NOACs over warfarin, or one NOAC over another. Indeed, choice of the anticoagulation regimen should be personalized based on the relative efficacy and safety of different agents across subgroups stratified by thrombotic and bleeding risk, as well as on other clinical factors, including anticoagulation control on warfarin, drug interactions, compliance and need for coagulation monitoring. This review appraises i) the randomized evidence on approved NOACs versus warfarin in AF across subgroups stratified by risk factors of stroke and bleeding and by the anticoagulation level reached on warfarin; and ii) clinical factors impacting on the anticoagulation regimen selection.     

老年非瓣膜病性心房颤动患者华法林钠抗凝疗效及安全性研究

目的探讨老年非瓣膜病性心房颤动（AF）患者华法林钠（华法林）抗凝治疗的安全性和有效性。方法160例老年（≥75岁）非瓣膜病性持续性AF患者,随机分入调整剂量华法林组和阿司匹林（300mg／d）组。观察国际标准化比值（INR）1．80～2．50时华法林剂量、血栓栓塞事件与出血风险。结果INR1．80～2．50时华法林剂量1．43～3．57mg／d,平均（2．373±0．304）mg／d。160例患者中,发生血栓栓塞13例（8．1％）。其中华法林组2例（2．5％）,阿司匹林组11例（13．8％）,两组间差异有统计学意义（P〈0．05）。轻微出血：华法林组7例（8．8％）,阿司匹林组5例（6．3％）,差异无统计学意义（P〉0．05）;两组均无严重出血。结论严密监测INR情况下,老年AF患者应用华法林抗凝治疗是安全有效的。     

Nonsteroidal anti-inflammatory drugs and bleeding risk in anticoagulated patients with atrial fibrillation

Although nonsteroidal anti-inflammatory drugs (NSAIDs) have generally conferred increased gastrointestinal bleeding risk, the data for bleeding risks with these drugs in anticoagulated atrial fibrillation (AF) patients per se were much more limited. Recent evidence shows that concomitant use of NSAIDs in anticoagulated AF patients carries a real risk of serious bleeding, as well as thromboembolism. Thus, physicians should clearly exercise extra caution with NSAIDs in patients with AF, especially if they are anticoagulated. Also, AF patients with NSAIDs should also undergo regular clinical review, and clinicians should regularly reassess the need for NSAID use. Finally, as a part of regular clinical assessment, bleeding risk should be routinely assessed, and the HAS-BLED score is now recommended in many guidelines for this purpose.     

The patterns of anticoagulation control and the risk of stroke,bleeding and mortality in patients with non‐valvular atrial fibrillation

Summary. Background: Anticoagulation control is often summarized using the percentage of time spent in a therapeutic range (TTR). This method does not describe the timing and severity of fluctuations in the International Normalised Ratio (INR).Objective: To evaluate whether the TTR method can be improved by considering the patterns of INR over time.Methods: The cohort included adults aged 40+ years with atrial fibrillation (AF) and laboratory records of INR as recorded in the UK Clinical Practice Research Datalink. Statistical clustering techniques based on simple INR measures were used to describe the patterns of INR. Nested case–control studies calculated the odds ratios (ORs) for the risk of stroke, bleeding and mortality with TTR and different INR patterns. It was also evaluated whether cluster analyses improved the prediction of outcomes over TTR.Results: A number of 27 381 patients were studied with a mean age of 73 years. The OR for mortality was 3.76 (95% confidence interval [CI] 3.03–4.68) in patients with < 30% TTR compared with patients with 100% TTR. INR patterns were found to be best described by six different clusters. The cluster with the most unstable pattern was associated with the largest risk of mortality (OR 10.7, 95% CI 8.27–13.85) and stroke (OR 3.42, 95% CI 2.08–5.63). INR measures that predicted death independent of the TTR‐included absolute difference between two subsequent INR measurements and change relative to the mean over time.Conclusion: Cluster analysis of INR patterns improved the prediction of clinical outcomes over TTR and may help to identify warfarin users who need additional anticoagulation monitoring.     

Value of pacemaker atrial diagnostic data in patients with paroxysmal atrial fibrillation: an opportunity to improve rates of warfarin utilization

Atrial diagnostic data within implantable devices provide an opportunity to assess the frequency and quantity of atrial fibrillation (AF) episodes (AF burden) and its impact on appropriate warfarin anticoagulation. Cardiologists were given clinical scenarios to review with different types of pacemaker diagnostic data in an elderly patient with risk factors for stroke. AF specific data was associated with increased warfarin utilization, but only at intermediate rates. Potential reasons and clinical implications are discussed.