Spanish Centre for Pharmacoepidemiologic Research (CEIFE), Madrid, Spain.
Department of Neurology, Odense University Hospital, Odense, Denmark.
Thromb Haemost. 2019 Jan;119(1):66-76. doi: 10.1055/s-0038-1676519. Epub 2018 Dec 31.
Many patients on warfarin therapy often present with supratherapeutic international normalized ratio (INR) levels, resulting from the influence of several patient-specific factors, which have been associated with adverse outcomes.
This article aims to identify risk factors for over-anticoagulation (INR levels ≥4) in a cohort of patients taking warfarin.
A cohort of warfarin users aged 18 to 85 years from January 2005 to April 2013 was identified in The Health Improvement Network U.K. primary care database ( = 12,506). A random date was assigned to all patients within their eligible person-time (index date), and a nested case-control analysis was performed with individuals presenting a first episode of INR level ≥4 after the index date used as cases ( = 699) and patients with non-supratherapeutic INR values (≤3) as controls ( = 9,798). Using unconditional logistic regression models, odds ratios with 95% confidence intervals were calculated adjusted for potential confounders. Two sensitivity analyses were performed with alternative definitions of over-anticoagulation (INR levels ≥5 or > 3).
Among the factors examined, the strongest predictors of over-anticoagulation were warfarin indication (in particular, valvular atrial fibrillation and valve replacement), renal failure (with the risk increasing steeply with decreasing estimated glomerular filtration rate), cancer, anaemia, respiratory infections treated with antibiotics, chronic obstructive pulmonary disease treated with β2-agonists, polypharmacy (≥10 medications), low socio-economic status and residency in rural areas. Similar results were obtained when supratherapeutic levels were defined as INR ≥5 or, alternatively, as INR > 3.
Predictors of supratherapeutic INR levels found in this study might help physicians identify patients where closer INR monitoring is warranted.
许多华法林治疗患者的国际标准化比值（INR）常常高于治疗范围，这是由多种患者特定因素的影响所致，这些因素与不良结局相关。
本研究旨在确定华法林使用者中出现过度抗凝（INR 水平≥4）的危险因素。
我们在英国初级保健数据库（The Health Improvement Network，THIN）中确定了 2005 年 1 月至 2013 年 4 月期间年龄为 18 至 85 岁的华法林使用者队列（ = 12506）。对所有患者在合格的个人时间内（索引日期）随机分配一个日期，并对在索引日期后首次出现 INR 水平≥4 的患者进行了嵌套病例对照分析（ = 699），并以 INR 值非超治疗范围（≤3）的患者作为对照（ = 9798）。使用非条件逻辑回归模型，调整潜在混杂因素后计算了比值比及其 95%置信区间。我们还进行了两项敏感性分析，分别使用替代的超治疗范围定义（INR 水平≥5 或 > 3）。
在所检查的因素中，过度抗凝的最强预测因素是华法林的适应证（尤其是心房颤动伴瓣膜病和瓣膜置换）、肾衰竭（随着估计肾小球滤过率的降低，风险急剧增加）、癌症、贫血、用抗生素治疗的呼吸道感染、用β2-激动剂治疗的慢性阻塞性肺疾病、多种药物合用（≥10 种药物）、社会经济地位低和居住在农村地区。当将超治疗范围定义为 INR≥5 或替代定义为 INR > 3 时，也得到了类似的结果。
本研究中发现的 INR 超治疗水平的预测因素可能有助于医生识别需要更密切监测 INR 的患者。
