高龄非瓣膜性房颤的华法林治疗11例体会

目的:探讨华法林治疗高龄非瓣膜性房颤患者安全有效的抗凝强度。方法:对11例高龄非瓣膜房颤有抗凝适应证者予华法林治疗,将抗凝强度控制在INR为1.5~2.0,观察疗效和出血并发症。结果:观察期间11例患者无致命性出血,仅1例皮肤出血且未停药。7例患者反复发作的短暂性脑缺血发作和脑梗塞症状得到控制。3例有2种以上危险因素的患者未出现栓塞并发症。结论:低抗凝强度(INR1.5~2.0)抗凝对高龄非瓣膜性房颤患者安全有效。     

Pharmacology,benefits, unaddressed questions,and pragmatic issues of the newer oral anticoagulants for stroke prophylaxis in non-valvular atrial fibrillation and proposal of a management algorithm

This systematic review aims to provide an update on pharmacology, efficacy and safety of the newer oral direct thrombin and factor Xa inhibitors, which have emerged for the first time in ~ 60 years as cogent alternatives to warfarin for stroke prophylaxis in non-valvular atrial fibrillation. We also discuss on four of the most common clinical scenarios with several unsolved questions and areas of uncertainty that may play a role in physicians' reluctance to prescribe the newer oral anticoagulants such as 1) patients with renal failure; 2) the elderly; 3) patients presenting with atrial fibrillation and acute coronary syndromes and/or undergoing coronary stenting; and 4) patients planning to receive AF ablation with the use of pulmonary vein isolation. New aspects presented in current guidelines are covered and we also propose an evidence-based anticoagulation management algorithm.     

Efficacy and safety of rivaroxaban compared with warfarin in patients with carotid artery disease and nonvalvular atrial fibrillation: Insights from the ROCKET AF trial

Background

Atrial fibrillation (AF) increases risk of stroke 5‐fold. Carotid artery disease (CD) also augments the risk of stroke, yet there are limited data about the interplay of these 2 diseases and clinical outcomes in patients with comorbid AF and CD.

Hypothesis

Among patients with both AF and CD, use of rivaroxaban when compared with warfarin is associated with a lower risk of stroke.

Methods

This post hoc analysis from ROCKET AF aimed to determine absolute rates of stroke/systemic embolism (SE) and bleeding, and the efficacy and safety of rivaroxaban compared with warfarin in patients with AF and CD (defined as history of carotid occlusive disease or carotid revascularization [endarterectomy and/or stenting]).

Results

A total of 593 (4.2%) patients had CD at enrollment. Patients with and without CD had similar rates of stroke or SE (adjusted hazard ratio [HR]: 0.99, 95% confidence interval [CI]: 0.66‐1.48, P = 0.96), and there was no difference in major or nonmajor clinically relevant bleeding (adjusted HR: 1.04, 95% CI: 0.88‐1.24, P = 0.62). The efficacy of rivaroxaban compared with warfarin for the prevention of stroke/SE was not statistically significant in patients with vs those without CD (interaction P = 0.25). The safety of rivaroxaban vs warfarin for major or nonmajor clinically relevant bleeding was similar in patients with and without CD (interaction P = 0.64).

Conclusions

Patients with CD in ROCKET AF had similar risk of stroke/SE compared with patients without CD. Additionally, there was no interaction between CD and the treatment effect of rivaroxaban or warfarin for stroke prevention or safety endpoints.     

阿哌沙班在心房颤动患者卒中预防中的应用

心房颤动(atrial fibrillation,AF)是卒中的独立危险因素.AF患者的卒中转归较差,致死率和致残率也较高.对于卒中风险较高的AF患者,需要应用抗凝药.阿哌沙班是近年来新出现的一种口服直接Xa因子抑制药.与华法林等传统抗凝药相比,阿哌沙班在预防AF患者卒中和全身性栓塞方面展现出一定的优势.     

Non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis

Background: Elderly population is known to be associated with polymedication, comorbidities and altered drug pharmacokinetics. However, the most adequate oral anticoagulant, attending to its relative efficacy and safety, remains unclear.Methods: We searched for phase III randomized controlled trials (MEDLINE, Cochrane Library, SciELO collection and Web of Science) comparing novel non-vitamin K antagonist oral anticoagulants (NOACs) with Vitamin K antagonists (VKA) in the elderly population (≥75 years-old) in atrial fibrillation (AF). Risk ratios (RR) were calculated using a random effects model. Trial sequential analysis (TSA) was performed in statistically significant results to evaluate whether cumulative sample size was powered.Results: Four trials rendered data about elderly (≥75 years-old) and younger patients (<75 years-old) with AF. NOACs demonstrated a 30% significant risk reduction (RR 0.70, 95% CI: 0.61 to 0.80) in elderly patients compared to VKA, without heterogeneity across studies (I² = 0%). The TSA showed that cumulative evidence of this subgroup exceeded the minimum information size required for the risk reduction. In younger patients, VKA and NOACs shared a similar risk of stroke and systemic embolism (RR 0.97, 95% CI: 0.79 to 1.18). Regarding major bleeding risk in the elderly, the overall comparative risk of NOACs was not different from VKA (RR 0.91, 95% CI: 0.72 to 1.16; I² = 86%).Conclusions: NOACs reduce significantly the risk of stroke and systemic embolism in elderly patients without increasing major bleeding events. The dimension of stroke risk reduction was significantly higher in the elderly than in younger adults.     

华法林在慢性心房颤动抗凝治疗中的应用

目的:探讨华法林在慢性心房颤动(CAf)抗凝治疗中的合理应用。方法:共入选234例具有血栓栓塞高风险的CAf患者,给予华法林抗疑治疗,监测国际标准化比值(INR)以调整华法林用量,随访观察华法林的不同起始剂量、不同的抗凝强度以及高龄(≥65岁)等因素对INR达标时间、INR稳定值、华法林维持量、出血率及栓塞率的影响。结果:分别采用开始剂量为普通剂量(2．5mg／d)与小剂量(1．25 mg／d)2种方式,两者最终获得稳定的INR、华法林维持量及出血率均差异无统计学意义,但前者能明显缩短INR首次达标时间及获得INR 稳定值的时间(均P<0．01),并有降低栓塞率的趋势;与低强度抗凝相比,中强度抗凝能显著降低栓塞率(P< 0．05),虽然伴出血率明显升高(P<0．05),但无严重出血发生;在相同的目标INR内,高龄患者出血率并不增加,但所需的华法林维持量有所降低(P<0．01)。结论:以普通量的华法林开始CAf抗凝治疗是安全的,抗栓塞效果优于小剂量;对具有栓塞高风险的CAf需保持中强度抗凝水平;华法林抗凝治疗并不增加高龄患者的出血风险。     

华法林对老年持续性房颤患者的疗效

目的:探讨华法林对老年房颤(AF)患者的疗效和安全性。方法:选择2014年1月至2016年12月于我院治疗的老年AF患者100例。按照随机对照原则,患者被分为华法林组(51例)和阿司匹林组(49例),两组均随访治疗1年。观察比较两组终点事件发生率和不良反应发生率。结果:阿司匹林组失访1例。终点事件:华法林组:脑梗死2例;阿司匹林组:脑梗死7例、外周血管栓塞2例、死亡1例。华法林组终点事件总发生率显著低于阿司匹林组(3.92%比20.83%,P=0.010)。不良反应:华法林组:皮肤瘀斑3例、牙龈出血1例;阿司匹林组:黑便3例,两组总不良反应发生率无显著差异(P=0.934)。结论:华法林能显著降低老年AF患者终点事件的发生率,值得推广应用。     

Initial apixaban dosing in patients with atrial fibrillation

Background

Apixaban is a non–vitamin K oral anticoagulant approved for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). Current labeling recommends dose reduction based on patient age, weight, and renal function.

Hypothesis

The aim of this study was to analyze adherence to current labeling instructions concerning initial apixaban dosing in clinical practice and identify factors associated with inappropriate dose reduction.

Methods

Patients with AF initiated on apixaban in 2016 were identified in the Heart Center Leipzig database. Records were screened to identify patient characteristics, prescribed apixaban dose, renal function, and further dosing‐relevant secondary diagnoses and co‐medication.

Results

We identified 569 consecutive patients with AF initiated on apixaban. In 301 (52.9%) patients, apixaban was prescribed in standard dose (5 mg b.i.d.) and in 268 (47.1%) in a reduced dose (2.5 mg b.i.d.). Of 268 patients receiving a reduced dose, 163 (60.8%) did not meet labeling criteria for dose reduction. In univariate and multivariate regression analysis, age (OR: 0.736, 95% CI: 0.664–0.816, P < 0.0001), patient weight (OR: 1.120, 95% CI: 1.076–1.166, P < 0.0001), and serum creatinine level (OR: 0.910, 95% CI: 0.881–0.940, P < 0.0001) were independent predictors for apixaban underdosage.

Conclusions

In clinical practice, apixaban dosing is frequently inconsistent with labeling. Factors associated with inappropriate dose reduction are age, patient weight, and serum creatinine level, the same factors used as criteria for dose adjustment. However, in underdosed patients, the 3 factors did not meet the criteria for dose reduction.     

Apixaban in patients with atrial fibrillation and prior coronary artery disease: Insights from the ARISTOTLE trial

Background

A substantial portion of patients with atrial fibrillation (AF) also have coronary artery disease (CAD) and are at risk for coronary events. Warfarin is known to reduce these events, but increase the risk of bleeding. We assessed the effects of apixaban compared with warfarin in AF patients with and without prior CAD.

Methods and results

In ARISTOTLE, 18,201 patients with AF were randomized to apixaban or warfarin. History of CAD was defined as documented CAD, prior myocardial infarction, and/or history of coronary revascularization. We analyzed baseline characteristics and clinical outcomes of patients with and without prior CAD and compared outcomes by randomized treatment using Cox models. A total of 6639 (36.5%) patients had prior CAD. These patients were more often male, more likely to have prior stroke, diabetes, and hypertension, and more often received aspirin at baseline (42.2% vs. 24.5%). The effects of apixaban were similar among patients with and without prior CAD on reducing stroke or systemic embolism and death from any cause (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.71–1.27, P for interaction = 0.12; HR 0.96, 95% CI 0.81–1.13, P for interaction = 0.28). Rates of myocardial infarction were numerically lower with apixaban than warfarin among patients with and without prior CAD. The effect of apixaban on reducing major bleeding and intracranial hemorrhage was consistent in patients with and without CAD.

Conclusions

In patients with AF, apixaban more often prevented stroke or systemic embolism and death and caused less bleeding than warfarin, regardless of the presence of prior CAD. Given the common occurrence of AF and CAD and the higher rates of cardiovascular events and death, our results indicate that apixaban may be a better treatment option than warfarin for these high-risk patients.     

Perioperative venous thromboembolic disease and the emerging role of the novel oral anticoagulants: An analysis of the implications for perioperative management

Venous thromboembolism includes 2 inter-related conditions: Deep venous thrombosis and pulmonary embolism. Heparin and low-molecular-weight heparin followed by oral anticoagulation with vitamin K agonists is the first line and current accepted standard therapy with good efficacy. However, this therapeutic strategy has many limitations including the significant risk of bleeding and drug, food and disease interactions that require frequent monitoring. Dabigatran, rivaroxaban, apixaban, and edoxaban are the novel oral anticoagulants that are available for use in stroke prevention in atrial fibrillation and for the treatment and prevention of venous thromboembolism (HYPERLINK\l ”1). Recent prospective randomized trials comparing the NOACs with warfarin have shown similar efficacy between the treatment strategies but fewer bleeding episodes with the NOACs. This paper presents an evidence-based review describing the efficacy and safety of the new anticoagulants compared to warfarin.     

城郊高龄老年房颤患者华法林治疗的安全性

目的：探讨城郊高龄老年房颤患者应用华法林的安全性.方法：选择100例资料完整的老年房颤患者,按照数字表法,被随机分为华法林组（51例）：华法林起始剂量1.25 mg,1次/d.每隔3d测定血浆凝血酶原时间国际标准化比值（INR）1次.2～4周达到目标范围,如INR未达标,每隔1周增加华法林0.625 mg,直到INR控制在2.0～3.0.INR稳定前门诊随访每周监测1次,INR稳定后每4周监测1次;阿司匹林组（49例）：阿司匹林,100 mg,1次/d.结果：与阿司匹林组比较,华法林组血栓栓塞等终点事件发生率明显降低（19.15％比3.92％,P=0.017）,出血等不良反应发生率无显著差异（4.25％比5.88％,P＞0.05）.结论：高龄老年房颤患者应用华法林,能显著降低栓塞发生率,而且是安全的.