Benefit-Risk Assessment of Rivaroxaban in Older Patients With Nonvalvular Atrial Fibrillation or Venous Thromboembolism.

IF 3.4 3区 医学 Q2 GERIATRICS & GERONTOLOGY
Paul P Dobesh, Albert A Volkl, Ákos Ferenc Pap, C V Damaraju, Bennett Levitan, Zhong Yuan, Alpesh N Amin
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引用次数: 0

Abstract

Background: Both bleeding and adverse ischemic events increase with age, compounding the benefit-risk balance of anticoagulants in older patients. We present analyses using benefit-risk methods to better understand the age-dependence of the benefit-risk profile of rivaroxaban in patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE).

Methods: Randomized controlled trial data from the ROCKET-AF (NVAF) and EINSTEIN DVT, EINSTEIN PE, EINSTEIN-Extension, and EINSTEIN CHOICE in (VTE) were used. For ROCKET-AF, benefits and risks were assessed with incidence rates for key thrombotic and bleeding endpoints and a net clinical benefit (NCB) measure. Cumulative incidences (estimated by the Kaplan-Meier method) were estimated at day 185 for EINSTEIN and EINSTEIN Extension and 1 year for EINSTEIN CHOICE. Incidence differences were calculated for the overall population and age subgroups of < 65, 65-75, and > 75 years.

Results: In ROCKET-AF, rate differences in the composite NCB outcome (vascular death, stroke, myocardial infarction, fatal bleeding, critical organ bleeding, and non-CNS systemic embolism) favored rivaroxaban overall and by age < 65, 65-75, and > 75 years (-84, -25, -61, and -150 cases per 10,000 patient-years, respectively). In the pooled EINSTEIN DVT and EINSTEIN PE studies, cumulative incidence differences for the composite NCB outcome (recurrent VTE and major bleeding) were -103, 3, -105, and -544 per 10,000 patients, respectively. For extended VTE treatment with rivaroxaban versus placebo in EINSTEIN-Extension, NCB results were -536, -492, -556, and -601 per 10,000 patients, respectively. In the EINSTEIN CHOICE analysis, NCB favored rivaroxaban 20 mg versus aspirin (-284, -255, -339, and -338, respectively) and rivaroxaban 10 mg versus aspirin (-339, -328, -485, and -80, respectively).

Conclusions: This analysis demonstrated a positive benefit-risk profile with rivaroxaban versus trial comparators in older patients with NVAF or VTE, with benefit-risk increasingly favoring rivaroxaban with increasing age.

Clinical trial registration: http://ClinicalTrials.gov , identifiers: NCT00403767 (ROCKET-AF), NCT00440193 (EINSTEIN DVT), NCT00439777 (EINSTEIN PE), NCT00439725 (EINSTEIN Extension), and NCT02064439 (EINSTEIN CHOICE).

利伐沙班治疗老年非瓣膜性房颤或静脉血栓栓塞患者的获益-风险评估
背景:出血和缺血性不良事件都随着年龄的增长而增加,这使得老年患者使用抗凝剂的获益-风险平衡更加复杂。为了更好地了解利伐沙班对非瓣膜性房颤(NVAF)或静脉血栓栓塞(VTE)患者的获益-风险特征的年龄依赖性,我们采用获益-风险方法进行了分析。方法:采用ROCKET-AF (NVAF)与EINSTEIN DVT、EINSTEIN PE、EINSTEIN- extension、EINSTEIN CHOICE in (VTE)的随机对照试验数据。对于ROCKET-AF,通过关键血栓和出血终点的发生率和净临床获益(NCB)指标来评估获益和风险。累积发病率(通过Kaplan-Meier方法估计)在EINSTEIN和EINSTEIN Extension的185天估计,而EINSTEIN CHOICE的1年估计。计算总体人群和年龄亚组< 65岁、65-75岁和75岁以下人群的发病率差异。结果:在ROCKET-AF中,综合NCB结局(血管性死亡、卒中、心肌梗死、致死性出血、危重器官出血和非中枢神经系统系统性栓塞)的比率差异总体上和年龄< 65岁、65-75岁和75岁(分别为-84、-25、-61和-150例/ 10,000患者年)有利于利伐沙班。在汇总的EINSTEIN DVT和EINSTEIN PE研究中,复合NCB结局(复发性静脉血栓栓塞和大出血)的累积发生率差异分别为-103、3、-105和-544 / 10000例患者。在EINSTEIN-Extension中,利伐沙班与安慰剂延长静脉血栓栓塞治疗,NCB结果分别为-536、-492、-556和-601 / 10000例患者。在EINSTEIN CHOICE分析中,NCB倾向于利伐沙班20mg vs阿司匹林(分别为-284、-255、-339和-338),利伐沙班10mg vs阿司匹林(分别为-339、-328、-485和-80)。结论:该分析表明,在老年非瓣膜性房颤或静脉血栓栓塞患者中,利伐沙班与试验比较物的获益-风险比为正,随着年龄的增长,利伐沙班的获益-风险比越来越有利。临床试验注册:http://ClinicalTrials.gov,标识符:NCT00403767 (ROCKET-AF)、NCT00440193 (EINSTEIN DVT)、NCT00439777 (EINSTEIN PE)、NCT00439725 (EINSTEIN Extension)、NCT02064439 (EINSTEIN CHOICE)。
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来源期刊
Drugs & Aging
Drugs & Aging 医学-老年医学
CiteScore
5.50
自引率
7.10%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Drugs & Aging delivers essential information on the most important aspects of drug therapy to professionals involved in the care of the elderly. The journal addresses in a timely way the major issues relating to drug therapy in older adults including: the management of specific diseases, particularly those associated with aging, age-related physiological changes impacting drug therapy, drug utilization and prescribing in the elderly, polypharmacy and drug interactions.
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