Comparison of the real-life clinical outcomes of warfarin with effective time in therapeutic range and non-vitamin K antagonist oral anticoagulants: Insight from the AFTER-2 trial

It is unclear whether warfarin treatment with high time in therapeutic range (TTR) is as effective and safe as non-vitamin K antagonist oral anticoagulants (NOACs). It is crucial to compare warfarin with effective TTR and NOACs to predict long-term adverse events in patients with atrial fibrillation. We aimed to compare the long-term follow-up results of patients with atrial fibrillation (AF) who use vitamin K antagonists (VKAs) with effective TTR and NOACs. A total of 1140 patients were followed at 35 different centers for five years. During the follow-up period, the international normalized ratio (INR) values were studied at least 4 times a year, and the TTR values were calculated according to the Roosendaal method. The effective TTR level was accepted as >60% as recommended by the guidelines. There were 254 patients in the effective TTR group and 886 patients in the NOAC group. Ischemic cerebrovascular disease/transient ischemic attack (CVD/TIA), intracranial bleeding, and mortality were considered primary endpoints based on one-year and five-year follow-ups. Ischemic CVD/TIA (3.9% vs. 6.2%; P = 0.17) and intracranial bleeding (0.4% vs. 0.5%; P = 0.69), the one-year mortality rate (7.1% vs. 8.1%; P = 0.59), the five-year mortality rate (24% vs. 26.3%; P = 0.46) were not different between the effective TTR and NOACs groups during the follow-up, respectively. The CHA2DS2-VASC score was similar between the warfarin with effective TTR group and the NOAC group (3 [2-4] vs. 3 [2-4]; P = 0.17, respectively). Additionally, survival free-time did not differ between the warfarin with effective TTR group and each NOAC in the Kaplan-Meier analysis (dabigatran; P = 0.59, rivaroxaban; P = 0.34, apixaban; P = 0.26, and edoxaban; P = 0.14). There was no significant difference in primary outcomes between the effective TTR and NOAC groups in AF patients.