服用华法林时个体患者处于治疗范围内时间的替代计算方法：ROCKET AF试验结果
Alternative calculations of individual patient time in therapeutic range while taking warfarin: results from the ROCKET AF trial.
作者信息
Singer Daniel E, Hellkamp Anne S, Yuan Zhong, Lokhnygina Yuliya, Patel Manesh R, Piccini Jonathan P, Hankey Graeme J, Breithardt Günter, Halperin Jonathan L, Becker Richard C, Hacke Werner, Nessel Christopher C, Mahaffey Kenneth W, Fox Keith A A, Califf Robert M
机构信息
Division of General Internal Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA (D.E.S.).
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (A.S.H., Y.L., M.R.P., J.P.P.).
出版信息
J Am Heart Assoc. 2015 Mar 3;4(3):e001349. doi: 10.1161/JAHA.114.001349.
BACKGROUND
In the ROCKET AF (Rivaroxaban-Once-daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter-INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow-up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial.
METHODS AND RESULTS
We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change-based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in-range INRs ("corrections") versus INRs that were out of range in the opposite direction ("overshoots"). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change-based approach, depending on assumptions. However, large inter-regional differences in anticoagulation control persisted.
CONCLUSIONS
TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow-up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change-based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter-regional differences previously reported.
CLINICAL TRIAL REGISTRATION
URL: ClinicalTrials.gov. Unique identifier: NCT00403767.
背景
在ROCKET AF（利伐沙班每日一次口服直接Xa因子抑制与维生素K拮抗剂预防房颤患者卒中及栓塞试验）试验中，以国际标准化比值（INR）的治疗范围内平均个体患者时间（iTTR）衡量的华法林抗凝控制存在显著的区域差异，这些差异与更长的INR检测间隔相关。如果随访INR检测间隔延长，标准的罗森达尔方法在适当剂量改变后可能会产生有偏差的低TTR估计值。我们探讨了更直接考虑剂量变化的TTR替代计算方法对ROCKET AF试验中平均iTTR区域差异的影响。
方法与结果
我们使用了一种考虑剂量变化的INR估算方法。我们比较了基于剂量变化的方法与标准罗森达尔方法之间的组平均iTTR值，并确定两种方法之间的差异取决于产生在范围内INR（“校正”）与相反方向超出范围的INR（“超调”）的剂量变化平衡。在ROCKET AF试验中，根据假设，使用基于剂量变化的方法，总体平均iTTR从55.2%（罗森达尔方法）增加了高达3.1%。然而，抗凝控制方面的区域差异仍然很大。
结论
TTR是华法林抗凝控制的标准衡量指标，取决于对绝大多数随访日的每日INR值进行估算。我们的TTR计算方法可能比罗森达尔方法更好地反映华法林剂量变化的影响。在ROCKET AF试验中，这种基于剂量变化的方法使总体平均iTTR略有增加，但并未实质性影响先前报道的较大区域差异。
临床试验注册
网址：ClinicalTrials.gov。唯一标识符：NCT00403767。
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