Introduction Current guideline suggests a switch from vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) in patients with low time in therapeutic range (TTR < 70%). Poor international normalized ratio (INR) control may be the result of poor compliance, and might therefore be associated with subsequent DOAC intake. Therefore, this study evaluates the effect of previous TTR and other measures of INR control on DOAC nonadherence and nonpersistence, in patients who switched from VKA to DOAC.

Methods A total of 437 patients who switched from VKA to DOAC between 2012 and 2019 were included using data from Certe Thrombosis Service, IADB.nl pharmacy community database University Groningen, and Statistics Netherlands. DOAC prescriptions were used to determine nonadherence and nonpersistence. INR control (i.e., TTR, time under therapeutic range [TUR], and INR variability) was assessed during the last 180 days of VKA use. Multivariable regression models were applied to determine the association between INR control and DOAC nonpersistence/nonadherence.

Results On VKA, 67.7% of the patients had a TTR below 70%. DOAC nonpersistence was 39.8% (95% confidence interval [CI]: 33.4–45.5%) during a median follow-up of 34.4 months (interquartile range: 19.1–49.2). Approximately 80% of persistent patients were DOAC-adherent. Low TTR was not associated with DOAC nonpersistence (hazard ratio: 1.14, 95% CI: 0.69–1.87) and DOAC nonadherence (odds ratio: 1.38, 95% CI: 0.67–2.84), nor were TUR and INR variability.

Conclusion Previous INR control during VKA therapy is not associated with subsequent DOAC nonadherence and nonpersistence. This study suggests that INR control on VKA cannot, and therefore should not, be used for predicting DOAC adherence or persistence.

简介 目前的指南建议，治疗范围内时间较短（TTR < 70%）的患者应从维生素 K 拮抗剂 (VKA) 转为直接口服抗凝剂 (DOAC)。国际标准化比率（INR）控制不佳可能是依从性差的结果，因此可能与随后的 DOAC 摄入有关。因此，本研究评估了从 VKA 转为 DOAC 的患者中先前的 TTR 和其他 INR 控制措施对 DOAC 不依从性和不持续性的影响。

方法 使用来自 Certe Thrombosis Service、IADB.nl 药房社区数据库格罗宁根大学和荷兰统计局的数据，纳入 2012 年至 2019 年间从 VKA 转为 DOAC 的 437 名患者。DOAC 处方用于确定不依从性和不坚持性。在使用 VKA 的最后 180 天期间评估 INR 控制（即 TTR、治疗范围内时间 [TUR] 和 INR 变异性）。应用多变量回归模型来确定 INR 控制与 DOAC 不坚持/不依从之间的关联。

结果 在 VKA 上，67.7% 的患者 TTR 低于 70%。在中位随访 34.4 个月期间，DOAC 不持续率为 39.8%（95% 置信区间 [CI]：33.4-45.5%）（四分位距：19.1-49.2）。大约 80% 的持续患者坚持 DOAC。低 TTR 与 DOAC 不坚持（风险比：1.14，95% CI：0.69-1.87）和 DOAC 不依从（比值比：1.38，95% CI：0.67-2.84）无关，TUR 和 INR 变异也没有相关性。

结论 VKA 治疗期间先前的 INR 控制与随后的 DOAC 不依从性和不持续性无关。这项研究表明，VKA 的 INR 控制不能、因此不应该用于预测 DOAC 依从性或持续性。