达比加群酯用于非瓣膜性房颤抗凝治疗的不良反应分析

目的:了解我院达比加群酯致药品不良反应发生的规律和特点,为临床安全合理使用达比加群酯提供参考依据.方法:采用回顾性分析方法,对我院2015年2月-2019年12月上报国家ADR监测中心的19例达比加群酯ADR报告进行统计分析.结果:19例达比加群酯ADR报告中,男女比例为1:1.7;61～70岁患者最多(42.11％)...     

华法林治疗非瓣膜性房颤的效果及安全性分析

目的探讨华法林治疗非瓣膜性房颤的临床效果及安全性。方法选择患者80例,分为两组,每组各40例,观察组给予华法林口服,对照组则给予阿司匹林,比较两组患者治疗后心脏彩超的检查结果,并统计发生缺血性脑卒中、全身性栓塞、大出血的情况。结果观察组患者的左室射血分数显著高于对照组（P〈0．05）,发生缺血性脑卒中、全身性栓塞、大出血的比例显著低于对照组（P〈0．05）。结论华法林抗凝可预防老年非瓣膜性房颤发生脑卒中、血管栓塞及大出血。提高心脏射血分数。     

Risk of stroke/systemic embolism,major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban,dabigatran or rivaroxaban compared with warfarin in the United States Medicare population

Objective: To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients.

Methods: Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts.

Results: Of the 186,132 eligible patients, 20,803 apixaban–warfarin pairs, 52,476 rivaroxaban–warfarin pairs, and 16,731 dabigatran–warfarin pairs were matched. Apixaban (hazard ratio [HR]?=?0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR?=?0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR?=?0.51; 95% CI 0.44, 0.58) and dabigatran (HR?=?0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR?=?1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs.

Conclusions: Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.     

华法林用于各卒中风险非瓣膜性房颤患者对其血栓栓塞与出血风险的影响

目的分析非瓣膜性房颤住院患者使用华法林进行抗凝治疗和国际标准化比值(INR)监测状况,以期更好地指导临床抗凝治疗,减少抗凝治疗中血栓栓塞和出血事件发生。方法收集2017年6-12月汕头大学医学院第一附属医院住院治疗的非瓣膜性房颤患者的临床资料、用药情况,监测患者住院期间INR值。采用CHA2DS2-VASc评分对所有患者进行卒中风险评估。随访2年,观察患者因血栓栓塞事件、出血事件再入院情况。结果本研究共纳入病例662例,其中144例使用华法林。在CHA2DS2-VASc评分分层中,中、高危卒中风险患者服用华法林组的INR处于1.5~2.5区间的比例高于无服用组(P<0.05)。在140例服用华法林且INR数据完整患者中,63例(45.0%)INR处于1.0~1.5区间,仅29例(20.7%)INR处于2.0~3.0区间;高危卒中风险患者INR在1.5~2.0组发生血栓栓塞、出血事件再次住院的比例低于INR非1.5~2.0组(P<0.05)。结论临床上华法林使用率低,抗凝强度低。对于中、高危卒中风险患者来说,正确服用华法林有助于将INR控制在1.5~2.5区间。当高危卒中患者的INR处于1.5~2.0区间时可减少血栓栓塞、出血风险的发生。     

基因分型指导非瓣膜性房颤患者华法林抗凝治疗的研究

目的:评价基因分型指导非瓣膜性房颤(NVAF)患者华法林抗凝治疗的有效性及安全性,探讨基因检测技术在华法林个体化治疗中的意义。方法:纳入符合条件的CHA₂DS₂-VASc≥2分(即卒中高危者)、无用药禁忌且初次使用华法林抗凝的NVAF患者,随机分为常规治疗组和个体化治疗组。常规治疗组给予华法林3 mg·d^-1起始治疗;个体化治疗组检测CYP2C9*2、CYP2C9*3和VKORC1(G-1639A)基因多态性,依据国际华法林遗传药理学联盟的权威公式计算的初始剂量进行治疗;两组常规监测INR,使INR维持在2.0~3.0之间;随访3个月,比较两组INR达标所需时间、主要出血/血栓栓塞事件的差异。结果:两组基线特征比较差异无统计学意义(P>0.05);个体化治疗组INR达标所需时间短(P<0.05);常规治疗组有1例发生脑卒中,6例发生轻微出血(牙龈/鼻腔出血、皮肤淤斑和血尿),两组比较差异有统计学意义(P<0.05)。结论:基于基因多态性的华法林初始剂量预测模型对实现华法林个体化治疗具有一定指导意义,INR达标时间更早且临床疗效更高。     

心房颤动合并冠心病冠状动脉介入治疗术后达比加群酯 抗凝治疗的有效性及安全性研究

目的 研究达比加群酯(dabigatran etexilate)在心房颤动(房颤)合并冠心病冠状动脉介入治疗(PCI)术后抗凝治疗中的有效性及安全性。方法 选取2015年3月至2016年3月安徽医科大学第二附属医院收治的房颤合并冠心病冠状动脉介入治疗病人90例,采用随机数字表法分为观察组和对照组,每组45例。观察组每天两次口服达比加群酯110 mg;对照组予以华法林治疗,调节国际标准化比值(INR)至2.0~3.0之间;同时两组均予以阿司匹林100 mg/d。观察随访12个月,比较两组病人实验室指标变化、新发急性心肌梗死、急性脑梗死、非中枢神经系统栓塞、出血事件及不良反应的发生率。结果 观察组中栓塞事件发生率(8.9%)与对照组(17.8%)相比差异无统计学意义(χ²=1.538,P=0.215);达比加群酯在降低与血栓形成有关的实验室指标上较华法林更优,同时观察组出血事件发生率低于对照组(χ²=4.406,P=0.036);两组在不良反应事件发生率上均差异无统计学意义(P>0.05)。结论 达比加群酯在房颤合并冠心病PCI术后病人抗凝治疗中与华法林的疗效相似,且达比加群酯的安全性更高,是此类病人抗凝治疗的理想选择。     

利伐沙班与华法林治疗非瓣膜性房颤的效果对比分析

目的 分析对比利伐沙班、华法林治疗非瓣膜性房颤(NVAF)的效果.方法 120例NVAF患者,依据随机法分为对照组和观察组,每组60例.对照组采用华法林治疗,观察组采用利伐沙班治疗.比较两组治疗效果、并发症发生情况以及治疗后血浆血小板微粒(PMP)、D-二聚体(D-D)、C反应蛋白(CRP)、N末端B型利钠肽前体(NT...     

住院心房颤动患者华法林的使用分析

目的分析比较瓣膜性心房颤动和非瓣膜性心房颤动住院患者华法林使用情况及国际标准化比值（INR）达标状况。方法收集969例住院心房颤动患者的病历资料进行回顾性分析。将患者分为瓣膜性心房颤动和非瓣膜性整体的心房颤动2组,分析2组华法林使用率和达标率的差异及应用华法林患者的INR达标水平。结果瓣膜性心房颤动患者161例中使用华法林者93例,占57.8%;非瓣膜性心房颤动患者808例中使用华法林者214例,占26.5%。93例使用华法林的瓣膜性心房颤动患者中,INR值在2.0～3.0者21例,占22.6%;214例使用华法林的非瓣膜性心房颤动患者中,INR值在2～3者38例,占17.8%。2组患者华法林的使用率比较差异有统计学意义（P＜0.05）,INR达标率比较差异无统计学意义（P＞0.05）。使用华法林的307例心房颤动患者的达标率INR在2.0～3.0者59例,占19.2%;INR＜2.0者230例,占74.9%;INR＞3.0者为18例,占5.9%。结论华法林在心房颤动患者中的使用率低且使用华法林后INR的达标率低。     

Strategies for improving dabigatran adherence for stroke prevention in patients with non-valvular atrial fibrillation: education and drug intake reminders (FACILITA study)

Objective To assess the efficacy of a mixed intervention, educational, and reminder calendar of the intake, as a strategy to improve therapeutic adherence with dabigatran in patients with non-valvular atrial fibrillation (NVAF).

Methods This was a prospective, longitudinal, multi-center study, carried out in 110 specialized healthcare centers in Spain. Seven hundred and twenty-six patients treated with dabigatran prescribed for stroke prevention were included. A cluster randomization was performed based on two groups: (1) Control Group (CG) as usual clinical practice, and (2) Intervention Group (IG) with a mixed strategy: (a) Healthcare education, and (b) Use of a reminder calendar for taking the anticoagulant medication. Three visits took place: baseline and follow-up at 6 and 12 months. Compliance was measured by using electronic monitors (MEMS). Average adherence percentage (%; Average AP) and daily compliance (%; Daily AP) was calculated. A patient was considered adherent when AP was 80–100%.

Results Six hundred and twenty-five patients completed the study (315 in the IG and 310 in the CG). Daily AP was 91.97% at 6 months and 91.05% after 12 months in the IG and 82.26% and 82.63% in the CG. Average adherence was 90.79% and 89.20% in the IG and 64.51% and 63.22% in the CG at 6 and 12 months, respectively. Significant differences were observed in the Daily AP and Average AP, with higher percentages in the IG. In the non-adherents group, the number of concomitant drugs, baseline, and 6 months SBP values, 6 and 12 months DBP values, and weight, total cholesterol, and LDL cholesterol were significantly higher. The number needed to treat (NNT) was 3.84 patients to prevent one non-adherence.

Conclusions A mixed intervention, consisting of patient education and a simple calendar reminder of drug intake, is an effective strategy to improve dabigatran therapeutic adherence in patients with NVAF. The percentage of adherence with dabigatran was high.     

Cost-effectiveness analysis of dabigatran versus rivaroxaban for stroke prevention in patients with non-valvular atrial fibrillation using real-world evidence in elderly US Medicare beneficiaries

Objective: Dabigatran and rivaroxaban have been approved by the US FDA to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients. Newly published real-world evidence based on the US population found that elderly Medicare patients with NVAF treated with rivaroxaban experienced statistically significant increases in intracranial hemorrhage (ICH) and major extracranial bleeding, and statistically nonsignificant decreases in thromboembolic stroke and acute myocardial infarction (AMI) compared with dabigatran. This study assessed the cost-effectiveness of dabigatran vs. rivaroxaban for the treatment of US Medicare NVAF patients.

Methods: A previously published Markov model was adapted to compare dabigatran and rivaroxaban. The model considered thromboembolic stroke, bleeding events, and AMI based on the published real-world event risks. Model outputs included clinical event rates, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).

Results: Dabigatran patients experienced fewer ICH and major extracranial bleeding events than rivaroxaban patients, but more stroke and AMI events. Dabigatran was found to yield lower costs and higher QALYs than rivaroxaban, with incremental costs of ?$3534 and incremental QALYs of 0.004. Results remained consistent in sensitivity analyses, with a positive net monetary benefit (willingness-to-pay thresholds of $50,000 and $100,000 per QALY) for dabigatran over rivaroxaban for all model inputs tested.

Conclusions: In this study using US Medicare real-world data, dabigatran was found to dominate rivaroxaban. The analyses were limited by the short follow-up period of the real-world data and results may not be generalizable to other patient populations.     

Long-term outcome in patients with non-valvular atrial fibrillation on dabigatran: a prospective cohort study

ABSTRACT

Introduction: Most studies on thromboembolic and bleeding risk in patients with non-valvular atrial fibrillation (NVAF) exposed to non-vitamin K oral anticoagulants stem from interrogation of insurance databases.

Areas covered: We studied 742 consecutive patients with NVAF who started treatment with dabigatran in three hospitals in Italy. Average follow-up was 1.80 years.

Mean age was 76.2 years. CHA₂DS₂VASc score was 0–1 in 37 (5%), 2 in 97 (13%) and ≥ 3 in 604 (82%) patients. NVAF was permanent in 349 (48%). Overall, 76% of patients remained on treatment over the entire follow-up period. Among 180 patients who discontinued permanently, the most frequent reasons were dyspepsia (33.9%), bleeding (17.8%), and renal worsening (12.1%). About 48% and 74% of permanent discontinuations occurred during the first 6 and 12 months of treatment, respectively. Rates of major events (per 100 patient-years) were 0.75 for stroke, 0.31 for myocardial infarction, 1.50 for all-cause death, and 1.80 for major bleedings. The rate of intracranial bleedings was 0.45 and that of major gastrointestinal bleedings was 0.75.

Expert opinion: This prospective cohort study confirms the low incidence of stroke, major bleeding and intracranial bleeding, and a 76% persistence with treatment, in patients with NVAF treated with dabigatran over about 2 years.     

Anticoagulation in patients with non-valvular atrial fibrillation: an evaluation of stability and early factors that predict longer-term stability on warfarin in a large UK population

ABSTRACT

Objective: To determine the proportion of patients with non-valvular atrial fibrillation (NVAF) treated with warfarin that achieved a 6‐month period within the target INR range (stability). To then evaluate any associations between stability and outcome and to determine whether stability can be predicted by clinical factors at an early stage in warfarin treatment.

Methods: This study was a record linkage study in 1513 patients with NVAF treated with warfarin for a minimum of 6‐months, carried out in a large UK population. The main outcome measures were stability (defined as six months within the target INR range [2.0–3.0]), thromboembolic and bleeding event rates and mortality. Secondary outcome measures were the predictive value of baseline characteristics and other treatment variables.

Results: Stability was achieved in 52% of the study group. Standardised mean survival was significantly higher in the group who achieved stability (? = 16.91 months, p < 0.001) with a hazard ratio of 4.36 (?p < 0.001). The stable group had a lower rate of both thromboembolic events (0.8% vs. 2.3% per patient year) and bleeds recorded on inpatient diagnoses (0.4% vs. 1.2% per patient year). Failure to achieve stable control was associated with age (Odds Ratio [OR] 1.011 (95% Confidence Interval [CI] 1.001–1.021)) and morbidity at baseline (OR 1.015; 95% CI 1.007–1.022). An increase in mean time between visits (OR 0.939; 95% CI 0.926–0.952) and the percentage time in range (OR 0.889; 95% CI 0.879–0.900) was associated with a decrease in the chance of instability. Greater variability in INR was also associated with a failure to achieve stability (OR 1.518; 95% CI 1.427–1.615). Receiver Operator Characteristic (ROC) analysis using data from the first three months of treatment demonstrated good discrimination of stability using age and morbidity at baseline and percentage time in range and frequency of visits during the first three months of treatment (area under curve [AUC] 0.780; standard error [SE] 0.012; 95% CI 0.757–0.803).

Conclusions: Many patients never achieved a period of 6‐months stability and were at increased risk of thromboembolic events and bleeds. Age, morbidity at baseline and variability of INR control in the first three months could be used to predict instability using warfarin. This study infers that patients should be treated more intensively in the early stages of warfarinisation in order to improve outcome.     

达比加群酯联合替格瑞洛对老年心房颤动合并不稳定型心绞痛患者的治疗效果

目的 探讨在治疗老年心房颤动合并不稳定型心绞痛时使用达比加群酯联合替格瑞洛对其凝血功能及临床疗效的影响.方法 120例老年心房颤动合并不稳定型心绞痛患者,按照入院的先后顺序分成观察组和对照组,每组60例.对照组在常规治疗的基础上口服华法林、替格瑞洛进行治疗,观察组在常规治疗的基础上加用达比加群酯联合替格瑞洛进行治疗.比...     

Insights from the dabigatran versus warfarin in patients with atrial fibrillation (RE-LY) trial

Oral anticoagulants such as warfarin have been used widely for the treatment of venous thromboembolism and stroke prevention in atrial fibrillation (AF) patients. Warfarin has significant limitations and also requires frequent monitoring. Thus, there is an unmet need, with the quest for alternative oral anticoagulants with stable pharmacokinetics and pharmacodynamics that do not need monitoring. The paper under evaluation provides us with up-to-date information on the safety and efficacy of a new oral anticoagulant, dabigatran, compared with warfarin for stroke prevention in AF patients.     

达比加群酯联合阿司匹林在非瓣膜性房颤治疗中的 应用效果及安全性评价

目的分析非瓣膜性心房颤动(房颤)患者使用达比加群酯联合阿司匹林进行治疗的临床疗效及安全性。方法120例非瓣膜性房颤患者,根据随机数字表法分为对照组和实验组,各60例。对照组患者采用常规抗凝治疗,实验组患者采用达比加群酯联合阿司匹林治疗。对比两组患者的治疗效果及不良反应发生情况。结果实验组患者的治疗总有效率为93.33%(56/60),高于对照组的73.33%(44/60),差异具有统计学意义(P<0.05)。实验组患者的不良反应发生率为23.33%(14/60),低于对照组的51.67%(31/60),差异具有统计学意义(P<0.05)。结论应用达比加群酯联合阿司匹林治疗非瓣膜性房颤可取得显著的疗效且安全性高,值得在临床上推广和应用。