Epistaxis y dabigatrán,nuevo anticoagulante oral no antagonista de la vitamina K

ObjectiveDabigatran is a new non-vitamin K antagonist (VKA) anticoagulant with anti-thrombin action, with supposedly fewer haemorrhagic complications. However, there are actually no established agents to reverse its effect, nor specific coagulation time tests for monitoring it.Materials and methodsAn observational prospective study was developed, noting epidemiological, clinical and therapeutic features among subjects with epistaxis treated with dabigatran. Results were compared with a group of epistaxis cases of individuals under anticoagulant therapy with VKA (acenocoumarol) and a control group without anticoagulation.ResultsSince its inclusion in our health system almost 3 years ago, 19 patients with epistaxis and concomitant use of dabigatran have been attended at the Emergency Unit in our hospital, as against 59 under VKA therapy and 144 without anticoagulation, with a mean admittance rate of 26%, 28% and 14%, respectively. In 3 out of 5 individuals admitted due to dabigatran treatment, previously unobserved renal failure was detected. Blood transfusion was needed in 80% of patients using dabigatran, 58% using VKA and 23% without anticoagulation. Invasive procedures to control nosebleed were required in 80%, 35% and 21%, respectively. Although haemorrhagic risk was lower in dabigatran cases, they showed the longest stay in the hospital when compared to the other groups.ConclusionsWith dabigatran, there are fewer cases of severe epistaxis than with acenocoumarol, but controlling them is more difficult.     

Direct Oral Anticoagulants Versus Vitamin K Antagonists in Real-life Patients With Atrial Fibrillation. A Systematic Review and Meta-analysis

Introduction and objectives

To assess the effectiveness of direct oral anticoagulants vs vitamin K antagonists in real-life patients with atrial fibrillation.

Severity of Gastrointestinal Bleeding in Patients Treated with Direct-Acting Oral Anticoagulants

Background

Direct-acting oral anticoagulants (DOACs), which have gained approval for stroke prevention in nonvalvular atrial fibrillation and treatment of venous thromboembolism, have become increasingly preferred over warfarin given their predictable pharmacodynamics, lack of required monitoring, and superior outcomes. Direct-acting oral anticoagulants have been shown to be associated with an increased frequency of gastrointestinal bleeding compared with warfarin, but the severity and characteristics of gastrointestinal bleeding in these patients is poorly understood.

达比加群酯治疗脑静脉血栓形成的有效性和安全性:与华法林的比较

目的比较达比加群酯与华法林治疗脑静脉血栓形成(cerebral venous thrombosis,CVT)安全性和有效性。方法回顾性分析2017年1月至2018年12月在河南省人民医院神经内科住院治疗的CVT患者的病历资料,根据用药情况分为达比加群酯组和华法林组。主要转归指标为治疗后6个月时的功能转归良好,定义为改良Rankin量表评分0~2分。次要转归指标包括受累静脉窦再通率以及出血发生率。结果共纳入152例CVT患者,其中达比加群酯组34例,华法林组118例。两组人口统计学和基线资料比较均差异无统计学意义。治疗6个月时,达比加群酯组和华法林组功能转归良好率(94.1%对93.2%;χ^2=0.043,P=0.836)以及受累静脉窦再通率(94.1%对93.2%;χ^2=0.043,P=0.836)均差异无统计学意义。达比加群酯组出血发生率显著低于华法林组(8.8%对27.1%;χ^2=4.985,P=0.026),两组轻微出血发生率差异无统计学意义(8.8%对16.1%;χ^2=0.618,P=0.432),但达比加群酯组严重出血发生率有显著低于华法林组的趋势(0%对11.0%;Fisher精确检验P=0.074)。达比加群酯组无死亡病例,华法林组死亡2例,其中1例妊娠期女性患者在治疗4个月时死于CVT复发,1例男性患者在治疗2个月时死于急性心肌梗死。两组病死率差异无统计学意义(0%对1.7%;Fisher精确检验P=1.000)。结论达比加群酯治疗CVT的有效性不逊于华法林,且出血并发症风险更低。     

Dabigatran and Warfarin for Secondary Prevention of Stroke in Atrial Fibrillation Patients: A Nationwide Cohort Study

Background

This register-based observational study compares dabigatran to warfarin for secondary stroke prevention in atrial fibrillation patients among both “new starters” on dabigatran and “switchers” to dabigatran from warfarin.

Methods

We identified, in nationwide Danish registries, 2398 patients with atrial fibrillation and a history of stroke/transient ischemic attack, making a first-time purchase of dabigatran 110 mg twice a day (bid; D110) and 150 mg bid (D150). Patients were categorized as either vitamin K antagonist (VKA) naive or experienced. Warfarin controls were identified using a complete (for VKA-naive dabigatran patients) or matched sampling approach (for VKA-experienced dabigatran patients). Subjects were followed for an average of 12.6 months for stroke and transient ischemic attacks. Confounder-adjusted Cox regression models were used to compare event rates between treatments.

Results

Among patients with a history of stroke/transient ischemic attack and prior VKA experience, switching to dabigatran was associated with an increased stroke/transient ischemic attack rate for both dabigatran doses compared with continuing on warfarin (D110 hazard ratio [HR] 1.99; 95% confidence interval [CI], 1.42-2.78; D150 HR 2.34; 95% CI, 1.60-3.41). Among prior stroke/transient ischemic attack patients who were new starters on dabigatran or warfarin, the rate of stroke/transient ischemic attack for both doses of dabigatran was similar to or lower than warfarin (D110 HR 0.64; 95% CI, 0.50-0.80; D150 HR 0.92l; 95% CI, 0.73-1.15).

Conclusions

In this register-based study, VKA-experienced patients with a history of stroke or transient ischemic attack who switched to dabigatran therapy had an increased rate of stroke compared with patients persisting with warfarin therapy.     

On the monitoring of dabigatran treatment in “real life” patients with atrial fibrillation

Introduction

The oral direct thrombin inhibitor dabigatran is increasingly used to prevent thromboembolic stroke in patients with atrial fibrillation (AF). Routine laboratory monitoring is currently not recommended, but measurements of dabigatran and/or its effect are desirable in certain situations. We studied dabigatran exposure and compared different tests for monitoring of dabigatran in a real-life cohort of AF patients.

Material and methods

Ninety AF patients (68 ± 9 years, 67% men, mean CHADS₂ score 1.5) were treated with dabigatran 150 (n = 73) or 110 mg BID (n = 17). Trough plasma concentrations of total and free dabigatran by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) were compared to indirect measurements by Hemoclot thrombin inhibitors (HTI) and Ecarin clotting assay (ECA), as well as PT-INR and aPTT.

Results

Total plasma dabigatran varied 20-fold (12–237 ng/mL with 150 mg BID) and correlated well with free dabigatran (r² = 0.93). There were strong correlations between LC-MS/MS and HTI or ECA (p < 0.001) but these assays were less accurate with dabigatran below 50 ng/mL. The aPTT assay was not dependable and PT-INR not useful at all. There were weak correlations between creatinine clearance (Cockcroft-Gault) and LC-MS/MS, HTI and ECA (p < 0.001 for all). A high body weight with normal kidney function was associated with low dabigatran levels.

Conclusions

HTI and ECA reflect the intensity of dabigatran anticoagulation, but LC-MS/MS is required to quantify low levels or infer absence of dabigatran. Most real life patients with a normal creatinine clearance had low dabigatran levels suggesting a low risk of bleeding but possibly limited protection against stroke.