Division of Cardiology, Duke University Medical Center, Durham, North Carolina.
Duke Clinical Research Institute, Durham, North Carolina.
JAMA Cardiol. 2019 Aug 1;4(8):756-764. doi: 10.1001/jamacardio.2019.1960.
Bleeding and thrombotic events (eg, stroke and systemic embolism) are common in patients with atrial fibrillation (AF) taking warfarin sodium despite a well-established therapeutic range.
To evaluate whether history of therapeutic warfarin control in patients with AF is independently associated with subsequent bleeding or thrombotic events.
DESIGN, SETTING, AND PARTICIPANTS: In this multicenter cohort study of 176 primary care, cardiology, and electrophysiology clinics in the United States, data were obtained during 51 830 visits among 10 137 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry; 5545 patients treated with warfarin were included in the bleeding analysis, and 5635 patients were included in the thrombotic event analysis. Patient follow-up was performed from June 29, 2010, to November 30, 2014. Data analysis was performed from August 4, 2016, to February 15, 2019.
Multiple measures of warfarin control within the preceding 6 months were analyzed: time in therapeutic range of 2.0 to 3.0, most recent international normalized ratio (INR), percentage of time that a patient had interpolated INR values less than 2.0 or greater than 3.0, INR variance, INR range, and percentage of INR values in therapeutic range.
Association of INR measures, alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the subsequent 6 months was assessed post hoc using logistic regression models.
A total of 5545 patients (mean [SD] age, 74.5 [9.8] years; 3184 [57.4%] male) with AF were included in the major bleeding analysis and 5635 patients (mean [SD] age, 74.5 [9.8] years; 3236 [57.4%] male) in the thrombotic event analysis. During a median follow-up of 1.5 years (interquartile range, 1.0-2.5 years), there were 339 major bleeds (6.1%) and 51 strokes (0.9%). Multiple metrics of warfarin control were individually associated with subsequent bleeding. After adjustment for clinical bleeding risk, 3 measures-time in therapeutic range (per 1-SD increase ≤55: adjusted odds ratio [aOR], 1.16; 95% CI, 1.02-1.32), variation in INR values (aOR, 1.32; 95% CI, 1.19-1.47), and maximum INR (aOR, 1.20; 95% CI, 1.10-1.31)-remained associated with bleeding risk. Adding INR variance to a clinical risk model slightly increased the C statistic from 0.68 to 0.69 and had a net reclassification improvement index of 0.028 (95% CI, -0.029 to 0.067). No INR measures were associated with subsequent stroke risk.
Three metrics of prior warfarin control were associated with bleeding risk but only marginally more so than traditional clinical factors. This study did not identify any measures of INR control that were significantly associated with stroke risk.
尽管华法林钠（warfarin sodium）在治疗范围内，但患有心房颤动（AF）的患者仍会经常发生出血和血栓事件（例如中风和全身性栓塞）。
评估 AF 患者既往华法林控制史是否与随后的出血或血栓事件独立相关。
设计、地点和参与者：在这项来自美国 176 个初级保健、心脏病学和电生理学诊所的多中心队列研究中，在 Outcomes Registry for Better Informed Treatment of Atrial Fibrillation（ORBIT-AF）登记处的 10137 例 AF 患者的 51830 次就诊中获得了数据；在出血分析中纳入了 5545 例接受华法林治疗的患者，在血栓事件分析中纳入了 5635 例患者。患者随访时间从 2010 年 6 月 29 日至 2014 年 11 月 30 日。数据分析时间为 2016 年 8 月 4 日至 2019 年 2 月 15 日。
分析了过去 6 个月内的多种华法林控制指标：2.0 至 3.0 之间的治疗时间范围、最近的国际标准化比值（INR）、患者的 INR 值小于 2.0 或大于 3.0 的时间百分比、INR 方差、INR 范围和 INR 值在治疗范围内的百分比。
事后使用逻辑回归模型评估 INR 测量值（单独或组合）与随后 6 个月内血栓事件和出血的临床因素和风险之间的关联。
在主要出血分析中纳入了 5545 例（平均[标准差]年龄，74.5[9.8]岁；3184[57.4%]为男性）AF 患者和 5635 例（平均[标准差]年龄，74.5[9.8]岁；3236[57.4%]为男性）血栓事件分析患者。中位随访时间为 1.5 年（四分位距，1.0-2.5 年），共有 339 例大出血（6.1%）和 51 例中风（0.9%）。华法林控制的多个指标与随后的出血独立相关。在调整临床出血风险后，3 项指标-治疗范围内的时间（每增加 1-SD，≤55：调整后的优势比[aOR]，1.16；95%CI，1.02-1.32）、INR 值的变化（aOR，1.32；95%CI，1.19-1.47）和最大 INR 值（aOR，1.20；95%CI，1.10-1.31）-与出血风险相关。在临床风险模型中加入 INR 方差略微提高了 C 统计量从 0.68 到 0.69，净重新分类改善指数为 0.028（95%CI，-0.029 至 0.067）。没有 INR 指标与随后的中风风险相关。
过去华法林控制的三个指标与出血风险相关，但与传统临床因素相关的程度仅略高。这项研究没有发现任何 INR 控制指标与中风风险显著相关。
