The use of dabigatran immediately after atrial fibrillation ablation

Dabigatran After AF Ablation. Introduction: Atrial fibrillation (AF) ablation requires postprocedural anticoagulation to prevent thromboembolic events because of the ablation procedure itself or due to recurrent AF postprocedure. Dabigatran is a new anticoagulant and may be useful after AF ablation to prevent thromboembolic events. Methods and Results: We evaluated 123 consecutive patients who were started on dabigatran after AF ablation. Patients were given enoxaparin 0.5 mg/kg at the end of the procedure, which was repeated 12 hours later and then discontinued. Dabigatran was started 22 hours postablation with drug dose based on renal function. Primary outcomes were thromboembolic events, bleeding complications, and side effects over a 30‐day follow‐up period. The preablation anticoagulant was warfarin in 56 (45.5%) patients, dabigatran in 34 (27.6%), and aspirin in 26 (21.1%). Seven (5.7%) patients were on no anticoagulant before ablation. The patients on dabigatran before ablation with normal renal function had the drug stopped 36 hours preablation. There were no preprocedural or intraprocedural thromboembolic episodes or bleeding. Three patients received dabigatran 75 mg bid and the rest 150 mg bid. There were no postablation strokes, transient ischemic attacks, or systemic thromboemboli in any patient. Three patients discontinued dabigatran and were changed to warfarin, 2 because of gastrointestinal side effects and 1 because of a diffuse rash. Conclusions: Dabigatran is safe and well tolerated after AF ablation. It did not cause bleeding complications and there were no thromboembolic events. Dabigatran appears to be an alternative to warfarin after AF ablation . (J Cardiovasc Electrophysiol, Vol. 23 p. 264‐268, March 2012.)     

达比加群酯对患者凝血功能的影响及相关影响因素分析

目的：调查患者使用达比加群酯治疗后凝血状况的变化,以及肝肾功能变化对凝血指标和出血情况的影响,为临床更好地使用达比加群酯提供参考依据。方法：收集中日友好医院2017年4月1日至2018年3月31日住院期间使用达比加群的患者信息,进行回顾性分析。通过分析患者的凝血指标、肝肾情况、出血情况,分析达比加群酯对这些指标的影响。结果：共收集患者247例,男性139例（56.28%）,女性108例（43.72%）,平均（72.11±29.26）岁。共有189例患者测定了便潜血,其中免疫法检测阳性或弱阳性患者32例（16.93%）,化学法检测阳性或弱阳性患者30例（15.87%）。共有220例患者测定了尿红细胞（高倍镜）,其中阳性患者30例（13.64%）。患者服用达比加群前后TT、APTT值变化十分明显。肾功能对APTT的影响无显著性差异。CrCL>50 mL·min^-1的患者免疫法、化学法便潜血阳性的患者比例分别为16.77%,15.48%,尿红细胞阳性患者比例为1.08%;30 ≤ CrCL ≤ 50 mL·min^-1的患者免疫法、化学法便潜血阳性的患者比例均为25.00%,尿红细胞阳性患者比例为9.52%;CrCL<30 mL·min^-1的患者免疫法、化学法便潜血阳性的患者比例均为22.00%,尿红细胞阳性患者比例为25.00%。肾功能损伤的患者出血风险增加,应注意应密切监测。ALT或AST一项或两项均升高组的患者服用达比加群后,免疫法、化学法便潜血阳性的患者比例均为29.17%,尿红细胞阳性患者比例为26.93%。相比于正常组患者分别升高了2倍和2.03倍,而尿红细胞阳性患者比例升高了2.22倍。结论：高龄、有出血史等高危患者使用达比加群时注意凝血功能监测,当APTT升高2倍以上时,注意是否有隐匿性出血。肾功能对APTT无明显影响,肝酶异常时APTT延长。肝肾异常患者使用达比加群时出血风险增大,注意监测。     

高效液相色谱法检测甲磺酸达比加群酯及有关物质

为了研究甲磺酸达比加群酯的有关物质,本研究合成了7个有关化合物,建立了相关的HPLC检测方法(以XBridge C₁₈为色谱柱,甲醇-0.01 mol/L磷酸二氢钾为流动相梯度洗脱,检测波长为310 nm),并对样品的溶解溶剂和进样体积进行了筛选。结果显示,所建立的HPLC分析方法能使达比加群酯和7个化合物达到完全分离,且重复性好,准确度高,适用于甲磺酸达比加群酯有关物质的检测。     

Dabigatran and rivaroxaban for prevention of venous thromboembolism--systematic review and adjusted indirect comparison

What is known and objective: Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta‐analysis, and adjusted indirect comparison. Methods: We searched PubMed, EMBASE, trial registries and regulatory documents through May 2009 for randomized controlled trials (RCTs) of dabigatran (150 and 220 mg daily) and rivaroxaban (10 mg daily) compared with enoxaparin (40–60 mg daily) in elective orthopaedic surgery. We used random effects meta‐analysis to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI) for the outcomes of total venous thromboembolism, VTE (deep venous thrombosis, non‐fatal pulmonary embolism and all‐cause mortality), and haemorrhagic adverse events (major and clinically relevant non‐major bleeds). Adjusted indirect comparison was used for the pooled RRs of dabigatran and rivaroxaban with enoxaparin as the common control. Results: Rivaroxaban was superior to enoxaparin for the prevention of venous thromoboembolism (RR 0·56, 95% CI 0·43–0·73, P < 0·0001), with a trend for increased haemorrhage (RR 1·26, 95% CI 0·94–1·69, P = 0·13). Dabigatran was not superior to enoxaparin for prevention of VTE (RR 1·12, 95% 0·97–1·29, P = 0·12), and did not reduce haemorrhage risk (RR 1·10, 95% 0·90–1·35, P = 0·32). Adjusted indirect comparison showed that rivaroxaban was superior to dabigatran in preventing VTE, RR 0·50 (95% CI 0·37–0·68), but with a slight trend towards increased haemorrhage RR 1·14 (95% CI 0·80–1·64). What is new and conclusion: Rivaroxaban may be more effective than dabigatran for prevention of VTE after elective orthopaedic surgery but might also slightly increase the risk of haemorrhage.     

Idarucizumab for dabigatran reversal: the first 6 months in a tertiary centre

This retrospective audit reviews patients on dabigatran presenting with bleeding or requiring urgent surgery in the Wellington region, whether they received idarucizumab appropriately and the outcome of episodes. Eighty patients were identified with bleeding or need for urgent surgery, 14 of which received idarucizumab. In patients who received idarucizumab, use was safe, effective and overall appropriate. Idarucizumab was underutilised with patients who could have benefited not receiving it; however, some patients who were treated may not have required it. Increased awareness and use may improve outcomes.     

新型口服抗凝药达比加群酯研究进展

达比加群酯是一种新型合成的直接凝血酶抑制剂,口服经胃肠吸收后,在体内转化为具有直接抗凝血活性的达比加群。现主要对达比加群酯的药理学、相关临床研究、临床应用前景进行综述。     

房颤危险分层及抗凝治疗研究进展

房颤(AF)是临床常见的心律失常,脑卒中是其主要并发症。临床治疗的重要环节是栓塞预防,而AF患者的栓塞危险分层有助于临床个体化治疗。本文分析权威指南的AF栓塞危险分层标准,综述达比加群酯、利伐沙班和阿哌沙班等新型抗凝药的临床应用研究进展。     

Evaluation of Dabigatran- and Warfarin-Associated Hemorrhagic Events Using the FDA-Adverse Event Reporting System Database Stratified by Age

Dabigatran and warfarin are oral anticoagulant drugs widely used for the prevention of stroke in patients with atrial fibrillation. The objective of this study was to evaluate the interaction between aging and dabigatran- and warfarin-induced gastrointestinal (GI) and nervous system hemorrhage using data available in the FDA Adverse Event Reporting System (FAERS) database.We analyzed reports of hemorrhagic events in the GI and nervous system recorded in the FAERS database between 2004 and 2014 using an adjusted reporting odds ratio (ROR).We demonstrated that dabigatran-associated GI hemorrhage was significantly increased in patients over the age of 80 years. The RORs of dabigatran increased with increasing age, although aging had little effect on warfarin-associated GI hemorrhage. The ROR for anticoagulant-associated nervous system hemorrhage was not significantly affected by aging, as compared to GI hemorrhage.Our results indicate that the excretion of dabigatran may be affected by aging, as compared to warfarin, likely due to renal function decline. Our results emphasize the need for physicians to closely monitor GI bleeding in aging patients, because it is closely related to renal function deterioration.     

Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin,but not in that induced by dabigatran etexilate

Summary. Background: Both established oral anticoagulants such as warfarin and newer agents such as dabigatran etexilate (DE) effectively prevent thromboembolic disease, but may provoke bleeding. Limited clinical data exist linking oral anticoagulant reversal and bleeding tendency, as opposed to surrogate laboratory markers. Objective: To quantify bleeding in warfarin‐anticoagulated and DE‐anticoagulated mice by tail transection with or without pretreatment with potential reversal agents: prothrombin complex concentrate (PCC); activated PCC (APCC); recombinant factor VIIa (rFVIIa); or murine fresh‐frozen plasma (FFP). Methods: CD1 mice were given warfarin or DE by gavage, and the effects on in vitro coagulation assays, volume of blood loss and the bleeding time following tail transection injury were evaluated with different reversal agents. Results: PCC (14.3 IU kg^?1), but not rFVIIa (3 mg kg^?1) or FFP (12 mL kg^?1), normalized blood loss and bleeding time in mice with warfarin‐induced elevations of mean prothrombin time at two intensities (prothrombin time ratios of either 4.3 or 24). Neither separate nor combined PCC and/or rFVIIa treatment nor APCC (100 U kg^?1) treatment significantly reduced blood loss in mice anticoagulated with 60 mg kg^?1 DE 75 min prior to tail transection. Both combined PCC plus rFVIIa treatment and APCC treatment significantly reduced bleeding time in the DE‐treated mice. Conclusions: Our data suggest that PCC treatment prevents excess bleeding much more effectively in warfarin‐induced coagulopathy than in DE‐induced coagulopathy.