Department of Cardiology Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark.
Department of Cardiology Copenhagen University Hospital, Herlev and Gentofte Hospital Gentofte Denmark.
J Am Heart Assoc. 2022 Mar 15;11(6):e024402. doi: 10.1161/JAHA.121.024402. Epub 2022 Mar 1.
Background Oral anticoagulation (OAC) is effective for stroke prevention in patients with atrial fibrillation. However, some patients experience stroke despite OAC therapy, and knowledge about the impact of prior treatment quality is lacking. Methods and Results Patients with atrial fibrillation on OAC therapy who had a first-time ischemic stroke were identified in the Danish Stroke Registry (2005-2018). Patients treated with vitamin K antagonist (VKA) therapy were compared according to the international normalized ratio just before stroke (international normalized ratio <2 [subtherapeutic], international normalized ratio 2-3 [therapeutic], international normalized ratio >3 [supratherapeutic]), and patients on underdosed, appropriately dosed, and overdosed direct OAC (DOAC) therapy were compared. Stroke severity was determined using the Scandinavia Stroke Scale (0-58 points), and the risk of very severe stroke (0-14 points) was analyzed by multivariable logistic regression. One-year mortality was determined using multivariable Cox regression. A total of 2319 patients with atrial fibrillation and stroke were included; 1196 were taking a VKA (subtherapeutic [46%], therapeutic [43%], supratherapeutic [11%]), and 1123 were taking DOAC (underdosed [23%], appropriately dosed [60%], and overdosed [17%]). Subtherapeutic and supratherapeutic VKA therapy (compared with therapeutic) and underdosed DOAC therapy (compared with appropriate and underdosed DOAC) patients were older, more often women, and more comorbid. Subtherapeutic VKA therapy was associated with very severe stroke (odds ratio [OR], 2.06 [95% CI, 1.28-3.31]), whereas supratherapeutic VKA therapy was not (OR, 1.24 [95% CI, 0.60-2.57]) compared with therapeutic VKA therapy. Patients on subtherapeutic and supratherapeutic VKA therapy had a higher 1-year mortality (hazard ratio [HR], 1.66 [95% CI, 1.29-2.13]); HR, 1.55 [95% CI, 1.08-2.22], respectively) than those on therapeutic VKA therapy. Treatment with underdosed or overdosed DOAC therapy was not associated with very severe stroke (OR, 1.27 [95% CI, 0.76-2.15]; OR, 0.73 [95% CI, 0.37-1.43], respectively) and was not associated with 1-year mortality (HR, 1.09 [95% CI, 0.83-1.44]; HR, 0.82 [95% CI, 0.57-1.18], respectively) than appropriate DOAC. Conclusions Half of the patients with atrial fibrillation with stroke were on inappropriate OAC therapy. Subtherapeutic VKA was associated with worse stroke severity and higher mortality rate than therapeutic VKA therapy. Neither underdosed nor overdosed DOAC was associated with worse outcomes in adjusted models compared with appropriately dosed DOAC. This study supports DOAC as a first-line therapy over VKA.
背景 口服抗凝剂（OAC）可有效预防房颤患者的中风。然而，尽管接受了 OAC 治疗，一些患者仍会发生中风，并且缺乏关于先前治疗质量影响的知识。
方法和结果 在丹麦中风登记处（2005-2018 年）中确定了正在接受 OAC 治疗且首次发生缺血性中风的房颤患者。根据中风前的国际标准化比值（INR）（INR<2[低于治疗范围]、INR2-3[治疗范围]、INR>3[高于治疗范围]）比较接受维生素 K 拮抗剂（VKA）治疗的患者，比较接受低剂量、适当剂量和高剂量直接口服抗凝剂（DOAC）治疗的患者。使用斯堪的纳维亚中风量表（0-58 分）确定中风严重程度，并使用多变量逻辑回归分析非常严重中风（0-14 分）的风险。使用多变量 Cox 回归确定一年死亡率。共纳入 2319 例房颤合并中风患者；1196 例服用 VKA（低于治疗范围[46%]、治疗范围[43%]、高于治疗范围[11%]），1123 例服用 DOAC（低剂量[23%]、适当剂量[60%]和高剂量[17%]）。与治疗范围相比，低于治疗范围和高于治疗范围的 VKA 治疗（与治疗范围相比）和低剂量 DOAC 治疗（与适当和低剂量 DOAC 相比）的患者年龄较大，女性较多，合并症较多。与治疗范围的 VKA 治疗相比，低于治疗范围的 VKA 治疗与严重中风（比值比[OR]，2.06[95%置信区间，1.28-3.31]）相关，而高于治疗范围的 VKA 治疗则没有（OR，1.24[95%置信区间，0.60-2.57]）。与治疗范围的 VKA 治疗相比，接受低于治疗范围和高于治疗范围的 VKA 治疗的患者一年死亡率更高（危险比[HR]，1.66[95%置信区间，1.29-2.13]；HR，1.55[95%置信区间，1.08-2.22]）。接受低剂量或高剂量 DOAC 治疗与严重中风（OR，1.27[95%置信区间，0.76-2.15]；OR，0.73[95%置信区间，0.37-1.43]）或一年死亡率（HR，1.09[95%置信区间，0.83-1.44]；HR，0.82[95%置信区间，0.57-1.18]）均无相关性，与适当剂量的 DOAC 相比。
结论 一半的房颤合并中风患者接受了不适当的 OAC 治疗。与治疗范围的 VKA 相比，低于治疗范围的 VKA 与更严重的中风严重程度和更高的死亡率相关。与适当剂量的 DOAC 相比，低剂量或高剂量的 DOAC 均与调整后的不良结局无关。这项研究支持 DOAC 作为 VKA 的一线治疗。
