基于生理药代动力学模型的老年人群利伐沙班临床剂量研究

目的:建立老年人利伐沙班生理药代动力学模型(PBPK),为临床用药剂量调整提供参考。方法:查阅相关文献,获得利伐沙班理化参数、药代动力学及临床研究数据。利用GastroPlus^TM软件建立健康成人模型并外推至老年人,采用视觉检验及折叠误差法对模型进行评估。PBPK模型模拟不同年龄分层的药代动力学特征,通过评估大出血风险,对老年人用药剂量提出调整建议。结果:75~85岁老年人群在服用单剂量20 mg利伐沙班片剂时的血浆药物暴露量是20~44岁年轻人的1.82倍, 大出血风险为4.71%,建议服用剂量调整为15 mg qd;45~59岁、60~74岁人群无需调整剂量。结论:该研究建立的利伐沙班PBPK模型可用于预测老年人群PK特征,并为临床用药调整剂量提供依据。     

不同剂量利伐沙班与DAPT联合治疗ACS支架植入术后合并高危血栓栓塞风险的NVAF患者的效果比较

目的 比较不同剂量利伐沙班与双联抗血小板治疗(DAPT)联合治疗急性冠脉综合征(ACS)支架植入术后合并高危血栓栓塞风险的非瓣膜性心房颤动(NVAF)患者的效果。方法 回顾性选取2017年1月—2022年6月乐山市人民医院收治的ACS支架植入术后合并高危血栓栓塞风险的NVAF患者370例作为研究对象。将采用利伐沙班20 mg/d+DAPT的123例患者作为高剂量组,利伐沙班15 mg/d+DAPT的137例患者作为中剂量组,利伐沙班10 mg/d+DAPT的110例患者作为低剂量组。统计比较3组患者在治疗期间发生主要不良心血管事件、出血事件、出血事件严重程度。结果 3组主要不良心血管事件发生率及总发生率比较,差异无统计学意义(P>0.05)。3组各项出血事件发生率比较,差异无统计学意义(P>0.05)。中剂量组、低剂量组出血事件总发生率低于高剂量组(P<0.016 7)。3组大出血、小出血发生率比较,差异无统计学意义(P>0.05)。中剂量组、低剂量组轻微出血发生率低于高剂量组(P<0.016 7)。结论 ACS支架植入术后合并高危血栓栓塞风险的NVAF患...     

利伐沙班在缺血性脑卒中合并小腿肌间静脉血栓形成患者中的疗效与安全性影响因素分析

目的：探讨利伐沙班在缺血性脑卒中（IS）合并小腿肌间静脉血栓（CMVT）患者中疗效与安全性的影响因素。方法：将134例IS合并CMVT患者根据利伐沙班剂量分为低剂量（10 mg·d^-1和15 mg·d^-1）组（n=80）和标准剂量（20 mg·d^-1）组（n=54）,收集并比较2组患者临床基线资料。随访记录治疗后的无效事件和出血事件,采用单因素和多因素Logistic回归分析危险因素,并建立风险预测模型。结果：低剂量组患者肌酐清除率（CrCl）<50 mL·min^-1、合用阿司匹林比例显著高于标准剂量组（P<0.05）,低密度脂蛋白胆固醇（LDL-C）>2.6 mmol·L^-1比例显著低于标准剂量组（P<0.05）。低剂量组患者治疗无效事件发生率明显高于标准剂量组、出血事件发生率明显低于标准剂量组（P<0.05）。多因素分析显示,标准剂量（20 mg·d^-1）是影响无效事件和出血事件的独立危险因素（P<0.05）,美国国立卫生研究院卒中量表（NIHSS）评分、合并冠心病是影响出血事件的独立危险因素（P<0.05）。出血事件联合预测因子Z=-3.642+1.341X_剂量+0.153X_NIHSS+1.334X_{合并冠心病},ROC曲线的AUC值为0.833,表明有良好的预测性能。结论：低剂量利伐沙班（10 mg·d^-1和15 mg·d^-1）可能更适合IS合并CMVT患者,临床应结合剂量、NIHSS评分、合并冠心病3种危险因素综合评估出血风险。     

利伐沙班导致出血事件的群体药动学模型建立及影响因素分析

目的：建立利伐沙班出血患者群体药动学模型并对出血事件的影响因素进行分析。方法：回顾性选取93例服用利伐沙班抗凝治疗发生出血事件的患者为研究对象,收集192例次利伐沙班稳态峰谷浓度数据,以非线性混合效应模型法建立群体药动学模型并以Bayesian反馈法计算药时曲线下面积（AUC）,同时分析该群体PK模型协变量与预估药物暴露量的相关性。结果：建立的群体药动学模型可对数据进行较好拟合,协变量肾小球滤过率（e-GFR）对清除率（CL）有显著影响,最终模型为CL=77.2×EGFR/71.56^θCLcr。协变量e-GFR和年龄影响利伐沙班的估算AUC和峰浓度（C_max）数值。结论：利伐沙班出血患者群体药动学模型稳定、有效。患者肾功能和年龄影响利伐沙班出血人群体内药物暴露量。     

利伐沙班在非瓣膜性房颤患者中的临床应用分析及建议

目的：制定利伐沙班在临床非瓣膜性房颤患者中应用的合理性评价标准和用药建议,为规范其临床合理应用提供依据。方法：汇总国内外利伐沙班相关指南、专家共识和文献,形成利伐沙班在非瓣膜性房颤患者中应用的合理性评价标准,回顾性调查某院2018年下半年非瓣膜性房颤住院患者中使用利伐沙班病例,通过纳入标准,将符合要求的病例按照评价标准进行合理性分析;通过发放调查问卷汇总医生和患者在使用利伐沙班过程中的关注点,针对性制定合理化用药建议。结果：2018年下半年,利伐沙班在非瓣膜性房颤住院患者中使用例数共计217例,实际统计分析病例106例,利伐沙班使用不合理率为19.81%（21/106）,以低剂量人群和特殊病理状态患者给药剂量和围手术期用药时机错误为主要原因,不良反应发生率为6.60%（7/106）,均为出血性不良反应;医生和患者在使用利伐沙班中的关注点多集中在监护指标、出血事件处理和用药注意事项等方面。结论：利伐沙班在临床非瓣膜性房颤患者中应用较广泛,其疗效良好,但仍然存在不合理用药情况,特别是在给药剂量和围手术期用药方面,临床药师应密切关注利伐沙班临床应用指南等的更新,制定合理性评价标准和用药建议,积极与医生和患者沟通,促进利伐沙班合理使用。     

低于说明书推荐剂量利伐沙班在亚洲NVAF患者中的研究进展

利伐沙班用于预防非瓣膜性房颤(non-valvular atrial fibrillation, NVAF)患者卒中已有明确的推荐剂量,但亚洲不同国家/地区批准用于NVAF患者卒中预防的利伐沙班推荐剂量存在差异。而且由于缺乏高证据级别的研究数据支持,目前亚洲相关研究对NVAF患者使用低于说明书推荐的利伐沙班剂量抗凝的有效性和安全性的评价存在不一致。本文对亚洲NVAF患者使用利伐沙班在各指南/共识中的应用剂量推荐、亚洲人群抗凝特点和临床研究现状等方面进行分析总结,为临床合理使用利伐沙班提供参考。     

高龄非瓣膜性房颤合并高血压冠心病患者长期应用利伐沙班治疗的有效性及安全性分析

目的:探究高龄非瓣膜性房颤合并高血压冠心病患者长期应用利伐沙班治疗的有效性及安全性.方法:选择采用利伐沙班治疗(设为观察组)及华法林治疗(设为对照组)的≥60岁非瓣膜性房颤合并高血压冠心病患者各30例,分析两组应用效果.结果:观察组治疗后小出血事件总发生率低于对照组(P<0.05);观察组非大出血事件、大出血事件总发生率、栓塞事件、消化道反应发生情况与对照组间比较(P>0.05);治疗后观察组PT、APTT水平与对照组比较(P<0.05),TT、FIB水平与对照组比较(P>0.05);观察组治疗前、后ALT、AST及TBIL与对照组比较(P>0.05).结论:高龄非瓣膜性房颤合并高血压冠心病患者长期应用利伐沙班治疗效果及安全性均较好.     

利伐沙班致出血风险因素分析及预测

目的： 分析服用利伐沙班后的出血不良反应与凝血指标和出血风险因素的相关性,以提高其临床用药的安全性。方法： 回顾性分析2018年12月至2019年12月复旦大学附属华东医院服用利伐沙班的176例住院患者资料,对可能引起出血不良反应的危险因素进行单因素及Logistic回归分析,并在此基础上建立出血风险预测模型。结果： 85例（48.30%）存在出血不良反应,其中实际观察到的出血不良反应39例,隐匿性出血不良反应46例。Logistic回归分析结果显示,凝血酶原时间（prothombin time,PT）、性别、联用非甾体抗炎药（NSAIDs）/抗血小板药物等4个影响因素对利伐沙班致出血不良反应有显著性影响（P<0.05）。进一步得到出血风险联合预测因子Y=-15.087+1.115×X_PT-1.468×X_性别+1.645×X_联合NSAIDs+1.395×X_{联合抗血小板药物},其ROC曲线的AUC值为0.880,表明具有较好的预测能力。约登指数计算结果显示PT值超过12.75 s （灵敏度为0.762,特异度为0.725）易出现出血不良反应事件。结论： 在服用利伐沙班时应加强患者出血风险因素的评估,以保证临床用药的安全性。     

利伐沙班与达比加群低剂量治疗非瓣膜性房颤患者有效性和安全性的Meta分析

目的:系统评价低剂量利伐沙班与达比加群在治疗非瓣膜性房颤患者中的有效性和安全性.方法:计算机检索中、英文数据库PubMed、EMBASE、Cochrane Library、MEDLINE、中国知网、万方、维普,收集低剂量利伐沙班与达比加群治疗非瓣膜性房颤有效性和安全性的队列研究,检索期限从建库至2021年8月.对符合纳入标准的研究进行资料提取和质量评价,采用Revman5.3软件进行统计学分析.结果:最终纳入了17篇研究.Meta分析结果显示:在有效性方面,利伐沙班与达比加群低剂量给药后卒中/全身性栓塞、心肌梗死发生率均无显著差异(P>0.05).在安全性方面,利伐沙班大出血、颅内出血、全因死亡风险均显著高于达比加群(P<0.05),而两组消化道出血风险无显著差异(P>0.05).亚组分析结果表明:欧洲和北美洲地区,两组卒中/全身性栓塞发生率无显著差异,利伐沙班大出血风险高于达比加群;亚洲地区,利伐沙班卒中/全身性栓塞发生率低于达比加群,但中国人群中两药无差异;两组大出血风险无显著差异.无论随访时间是否>1年,利伐沙班大出血风险均高于达比加群,且差异有统计学意义.结论:房颤患者超说明书低剂量给予达比加群的有效性与利伐沙班相似,而达比加群的安全性更高、死亡率更低;由于中国人群纳入的研究数过少,故该结论需谨慎对待.     

不同剂量利伐沙班对非瓣膜性房颤抗凝效果的影响

目的分析不同剂量利伐沙班对非瓣膜性房颤(NVAF)抗凝效果的影响。方法采用回顾性队列研究方法。收集医院心内科病区2017年3月至6月收治的201例接受利伐沙班抗凝治疗并拟行射频消融术的NVAF住院患者临床资料,采用单因素方差分析和多因素回归分析法评估不同剂量利伐沙班对NVAF患者的抗凝效果。结果患者的平均年龄[OR=5.573,95%CI(2.621,8.525),P<0.001],年龄≥65岁比例[OR=0.310,95%CI(0.162,0.594),P<0.001],预测肾小球滤过率(eGFR)水平(P=0.002),肾功能不全患者比例[OR=0.273,95%CI(0.126,0.593),P=0.001],房颤血栓危险度(CHA₂DS₂-VASc)评分(P=0.025)与利伐沙班用量显著相关;合并冠心病[OR=0.512,95%CI(0.280,0.937),P=0.029],联用阿司匹林[OR=0.102,95%CI(0.029,0.356),P<0.001]、氯吡格雷[OR=0.153,95%CI(0.055,0.423),P<0.001]、他汀类药物[OR=0.467,95%CI(0.265,0.823),P=0.008]、胺碘酮[OR=5.729,95%CI(2.106,15.586),P<0.001]、质子泵抑制剂[OR=1.909,95%CI(1.088,3.351),P=0.024]等药物的低剂量组和高剂量组有显著差异。使用不同剂量利伐沙班后患者凝血功能指标均在正常范围内,无须监测。患者住院期间共23例(11.44%)发生出血,研究后发现,利伐沙班引起的出血风险与其日剂量显著相关[OR=0.786,95%CI(0.637,0.970),P=0.025];此外,联用阿司匹林[OR=7.700,95%CI(1.150,51.556),P=0.035]和出血风险评分升高[OR=2.305,95%CI(1.044,5.091),P=0.039]可显著增加使用利伐沙班相关出血风险。结论利伐沙班日剂量、联用抗血小板药物和出血风险评分是导致NVAF患者出血的危险因素。     

Effectiveness and safety of rivaroxaban in nonvalvular atrial fibrillation: data from a contemporary Spanish registry

Objective: To ascertain the clinical profile, management and rates of thromboembolic and bleeding complications in a contemporary cohort of patients with nonvalvular atrial fibrillation (NVAF) on rivaroxaban treatment, with a particular focus on some subgroups of patients.

Methods: Retrospective study that included all NVAF patients who started treatment with rivaroxaban for the prevention of stroke or systemic embolism between December 2012 and December 2015. Rates of outcomes (stroke, nonfatal myocardial infarction, major bleeding, intracranial bleeding and death) during follow-up were calculated.

Results: A total of 732 patients (mean age 76.4?±?9.2?years; 54.5% women) were included. Comorbidities were common (hypertension 87.5%; diabetes 26.5%; renal insufficiency 24.6%; prior stroke/transient ischemic attack 16.8%). Mean CHA₂DS₂-VASc was 3.9?±?1.5 and HAS-BLED 2.3?±?0.9; 61.9% of patients were rivaroxaban naïve users. After a mean treatment period of 22.7?±?7.4?months, rates of stroke, nonfatal myocardial infarction, major bleeding, intracranial bleeding and death were 1.8, 1.0, 3.2, 0.4 and 5.5 events per 100 patient-years, respectively. Rates of stroke and death were higher in patients >75?years (vs. ≤75?years) and in patients with prior stroke/transient ischemic attack or renal insufficiency. Rates of major bleeding were higher among patients >75?years and in patients with prior stroke/transient ischemic attack.

Conclusions: In this contemporary Spanish cohort of NVAF patients on rivaroxaban, patients had many comorbidities, a high thromboembolic risk and a moderate bleeding risk. Overall, rates of stroke and bleeding complications were low and similar to other previous studies. These data suggest that rivaroxaban is effective and safe in routine practice.     

Impact of renal function on ischemic stroke and major bleeding rates in nonvalvular atrial fibrillation patients treated with warfarin or rivaroxaban: a retrospective cohort study using real-world evidence

Objectives: Renal dysfunction is associated with increased risk of cardiovascular disease and is an independent predictor of stroke and systemic embolism. Nonvalvular atrial fibrillation (NVAF) patients with renal dysfunction may face a particularly high risk of thromboembolism and bleeding. The current retrospective cohort study was designed to assess the impact of renal function on ischemic stroke and major bleeding rates in NVAF patients in the real-world setting (outside a clinical trial).

Methods: Medical claims and Electronic Health Records were retrieved retrospectively from Optum’s Integrated Claims–Clinical de-identified dataset from May 2011 to August 2014. Patients with NVAF treated with warfarin (2468) or rivaroxaban (1290) were selected. Each treatment cohort was stratified by baseline estimated creatinine clearance (eCrCl) levels. Confounding adjustments were made using inverse probability of treatment weights (IPTWs). Incidence rates and hazard ratios of ischemic stroke and major bleeding events were calculated for both cohorts.

Results: Overall, patients treated with rivaroxaban had an ischemic stroke incidence rate of 1.9 per 100 person-years (PY) while patients treated with warfarin had a rate of 4.2 per 100 PY (HR?=?0.41 [0.21–0.80], p?=?.009). Rivaroxaban patients with an eCrCl below 50?mL/min (N?=?229) had an ischemic stroke rate of 0.8 per 100 PY, while the rate for the warfarin cohort (N?=?647) was 6.0 per 100 PY (HR?=?0.09 [0.01–0.72], p?=?.02). For the other renal function levels (i.e. eCrCl 50–80 and ≥80?mL/min) HRs indicated no statistically significant differences in ischemic stroke risks. Bleeding events did not differ significantly between cohorts stratified by renal function.

Conclusions: Ischemic stroke rates were significantly lower in the overall NVAF population for rivaroxaban vs. warfarin users, including patients with eCrCl below 50?mL/min. For all renal function groups, major bleeding risks were not statistically different between treatment groups.     

Secondary prevention of stroke in patients with nonvalvular atrial fibrillation: optimal intensity of anticoagulation

Nonvalvular atrial fibrillation (NVAF) is frequently seen in elderly people and has become a main cause of cardioembolic stroke. The efficacy of anticoagulation for primary prevention of stroke or transient ischaemic attacks (TIAs) in patients with NVAF has been established by prospective, randomised and controlled trials. Warfarin decreased the frequency of all strokes by 68% and the rate of the combined outcome of stroke, systemic embolism or death by 48%. Anticoagulation with warfarin using international normalised ratios (INRs) ranging from 2.0 to 3.0 is recommended for patients with NVAF, who have any of the risk factors identified by the Atrial Fibrillation Investigators (AFI) [previous stroke or TIA, history of hypertension, diabetes mellitus, advanced age (> or = 65 years old), congestive heart failure and coronary artery disease], the American College of Chest Physicians (ACCP) [increased age (> 75 years old), prior stroke, hypertension and heart failure], or the Stroke Prevention in Atrial Fibrillation (SPAF) investigators [women > 75 years old, prior stroke, systolic blood pressure > 160mm Hg, recent heart failure, and fractional shortening < 25% on echocardiography]. For the secondary prevention of stroke, the efficacy of adjusted-dose warfarin therapy has been demonstrated by 2 major randomised trials. SPAF III (INR 2.0 to 3.0) demonstrated a lower incidence of ischaemic stroke or systemic embolism (3.4 %/year) compared with low fixed-dose warfarin plus aspirin (acetylsalicylic acid) [11.9%]. The European Atrial Fibrillation Trial [EAFT] (INR 2.5 to 4.0) showed a lower incidence of all stroke (4.0 %/year) with adjusted-dose warfarin compared with placebo (12.0 %/year). The incidence of major bleeding in the adjusted-dose warfarin group in SPAF III and EAFT was 2.4 and 2.8 %/year, respectively. EAFT incidence rates for the occurrence of a first ischaemic or haemorrhagic complication analysed by INR range indicated that the rate was lowest at INRs of 2.0 to 2.9, and higher with INRs of 3.0 to 3.9. Therefore, the optimal intensity of anticoagulation for prevention of recurrent stroke seems to be an INR of between 2.0 and 3.0, as for primary prevention. Retrospective and prospective studies from Japan reported that in the elderly, haemorrhagic complications occur frequently with INRs above 2.6 and major ischaemic events cannot be prevented at INRs below 1.6. Therefore, an INR target between 1.6 and 2.6 may be an alternative for secondary prevention of stroke in elderly patients with NVAF who have a potential risk of bleeding, to avoid both major ischaemic and haemorrhagic events. Antiplatelets may be administered in patients who are unable to manage taking warfarin properly or who have a high risk of falling and subsequently sustaining a head injury, although the efficacy of antiplatelets for secondary prevention of stroke in NVAF has not yet been established.     

介入治疗与利伐沙班抗凝治疗对伴卵圆孔未闭的隐源性卒中患者长期疗效的比较

摘要：目的 探讨介入治疗与利伐沙班抗凝治疗对伴卵圆孔未闭（PFO）的隐源性卒中患者预后的影响。方法 入选49例伴PFO的隐源性卒中患者随机分为介入治疗组（24例）和利伐沙班组（25例）,前者接受经皮PFO封堵术;后者接受利伐沙班抗凝治疗（10 mg/d）。观察主要终点事件为再发非致死性的缺血性脑卒中（包括短暂性缺血发作）或致死性的脑卒中、早期死亡（放置器械后30 d或随机分组后45 d内）及次要终点事件为全因死亡、周围血管栓塞、新发生的心律失常（如房颤）、心肌梗死及出血等。结果 2组患者平均随访时间（3.5±0.5）年,随访期间利伐沙班组和介入治疗组的失访率分别为8.3%（2/25）和16.6%（4/24）,差异无统计学意义（P＞0.05）。介入治疗组再发非致死性的缺血性脑卒中（短暂性缺血发作）1例,利伐沙班组3例,2组均未出现致死性脑卒中及早期死亡。介入治疗组和利伐沙班组无主要疗效终点事件累积生存率差异无统计学意义（P＞0.05）。介入治疗组新发房颤1例,房性早搏合并短阵房速者2例,但手术后24 h内均自发恢复为窦性心律;未出现心血管原因死亡、周围血管栓塞、心肌梗死及出血等事件。介入治疗组与利伐沙班组联合终点事件发生率分别为16.7%（4/24）、44%（11/25）,累积生存率差异有统计学意义（P＜0.05）。2组随访各时点NIHSS评分和mRS评分差异均无统计学意义。结论介入封堵治疗较利伐沙班治疗可更有效改善伴PFO的隐源性卒中患者的预后。     

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.     

利伐沙班治疗老年非瓣膜性心房颤动患者的有效性及安全性分析

目的探讨老年非瓣膜性心房颤动患者采用利伐沙班治疗的有效性及安全性。方法60例老年非瓣膜性心房颤动患者,依据抗凝治疗方法不同分为利伐沙班组和华法林组,各30例。利伐沙班组患者接受利伐沙班抗凝治疗,华法林组患者接受华法林抗凝治疗。比较两组患者的栓塞事件、出血事件、不良反应发生情况。结果利伐沙班组患者的栓塞事件发生率为10.0%(3/30),华法林组患者的栓塞事件发生率为13.3%(4/30),两组比较差异无统计学意义(P>0.05)。利伐沙班组患者的出血事件发生率为3.3%,低于华法林组的20.0%,差异具有统计学意义(P<0.05)。利伐沙班组患者的不良反应发生率为16.7%,低于华法林组的40.0%,差异具有统计学意义(P<0.05)。结论老年非瓣膜性心房颤动患者采用利伐沙班抗凝治疗的有效性及安全性较华法林高,更能有效降低患者的出血事件、不良反应发生率,值得推广。     

An early evaluation of bleeding-related hospital readmissions among hospitalized patients with nonvalvular atrial fibrillation treated with direct oral anticoagulants

Objective:

Clinical trials have demonstrated that direct oral anticoagulants (DOACs) are efficacious in reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF) with differences in the reduction of bleeding risks vs. warfarin. The objective of this study was to assess bleeding-related hospital readmissions among hospitalized NVAF patients treated with dabigatran, rivaroxaban, and apixaban in the US.

Research design and methods:

Patients (≥18 years) with a discharge diagnosis of NVAF who received apixaban, dabigatran, or rivaroxaban during hospitalization were identified from the Premier Hospital database (1 January 2012–31 March 2014) and the Cerner Health Facts hospital database (1 January 2012–31 August 2014). Patients identified from each database were analyzed separately and grouped into three cohorts depending on which DOAC was received. Patient characteristics, hospital resource use and costs, and frequency of readmissions within 1 month were evaluated.

Results:

Among study populations identified from the Premier database (N?=?74,730) and the Cerner database (N?=?14,201), patients who received apixaban were older, had greater comorbidity, and had higher stroke and bleeding risks. After controlling for patient characteristics, including comorbidity and stroke and bleeding risks, compared with patients who received apixaban during their index hospitalizations, the odds of bleeding-related hospital readmissions were significantly greater by 1.4-fold (p?<?0.01) for patients who received rivaroxaban and 1.2-fold (p?=?0.16) numerically greater for patients who received dabigatran among patients identified from the Premier Hospital database. Among patients in the Cerner Health Facts hospital database, bleeding-related hospital readmissions were significantly greater by 1.6-fold (p?=?0.04) for patients who received rivaroxaban and 1.3-fold (p?=?0.30) numerically greater for patients who received dabigatran compared to patients who received apixaban.

Limitations:

No causal relationship between treatment and outcomes can be concluded.

Conclusions:

NVAF patients using different DOACs had different characteristics, including stroke and bleeding risks. Use of rivaroxaban, compared to apixaban was associated with significantly greater risk of bleeding-related readmissions across two database claims analyses.     

Use of oral anticoagulants in older patients

Recently published American and British guidelines have comprehensively reviewed the indications for long term anticoagulation. The best evidence currently available supports the use of long term oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF), venous thromboembolic disease, ischaemic heart disease, mural thrombi, and mechanical heart valves. Selected patients with valvular heart disease, cerebral vascular disease, and peripheral arterial disease may also benefit from the use of these drugs. When no specific contraindications are present, elderly patients with either paroxysmal or persistent NVAF should be considered candidates for treatment with anticoagulants. Pooled analyses of the results from 9 randomised trials demonstrate that warfarin significantly reduces the risk of ischaemic stroke in patients with NVAF, particularly those in a 'high risk' category defined by the presence of additional clinical or echocardiographic risk factors. Long term anticoagulation does not appear to be justified in patients with NVAF considered to be at 'low risk' for stroke. Because the prevalence of NVAF and most other cardiovascular conditions increases with advancing age, many elderly patients will be candidates for thromboprophylaxis. The potential benefit of long term anticoagulation must be carefully weighed against the risk of serious haemorrhage in such patients. Bleeding complications with anticoagulant drugs appear to occur more frequently in older patients than in younger individuals. Advanced age (>75 years), intensity of anticoagulation [International Normalised Ratio (INR) >4.0], history of cerebral vascular disease (recent or remote), and concomitant use of drugs that interfere with haemostasis [aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory drugs] are among the most important variables in determining an individual's risk for major bleeding with anticoagulants. Older patients often display increased sensitivity to the effects of warfarin, both in the early induction phase and during the long term maintenance phase of therapy. Conditions such as congestive heart failure, malignancy, malnutrition, diarrhoea and unsuspected vitamin K deficiency, enhance the prothrombin time response. The decision to interrupt anticoagulant therapy before elective surgery in elderly patients should evaluate the thrombotic risk of such a manoeuvre versus the risk of bleeding if anticoagulants are continued. In non-surgical patients, excessively elevated INRs without associated haemorrhage can usually be managed by simply witholding one or several doses of warfarin. If more rapid reversal is needed, small doses of phytomenadione (vitamin K1) can be administered safely without overcorrection or the development of vitamin K-induced warfarin resistance.