Association between Time in Therapeutic Range (TTR) and Clinical Outcomes in Patients on Warfarin: A 7-year Retrospective Cohort Study

Objective: To evaluate the relationship between TTR and long-term clinical outcomes, focusing on the efficacy and safety of warfarin therapy. Materials and Methods: A retrospective cohort study (2015-2022) of 1,466 patients at Charoenkrung Pracharak Hospital. TTR was calculated using the Rosendaal method. Patients were categorized into two groups: good control (TTR ≥ 65%) and poor control (TTR < 65%). Efficacy outcomes included ischemic stroke or transient ischemic attack (TIA), systemic embolism (SE), and ischemic-related death. Safety outcomes included major bleeding, intracranial hemorrhage (ICH), and fatal bleeding. Cox proportional hazards regression was used to determine association between TTR and clinical outcomes. Results: Mean age was 68.8±13.3 years (52.2% female). Mean follow-up duration was 3.2±1.9 years, with a mean TTR of 56.36±25.34%. Three most common indications were atrial fibrillation/flutter (AF/AFL) (68.8%), venous thromboembolism (VTE) (9.4%), and mechanical heart valves (9.2%). Compared to the good control group, patients with poor control (TTR < 65%) had significantly higher incidence rates of both efficacy (1.29 vs. 0.56 per 100 person-years) and safety outcomes (4.69 vs. 2.92 per 100 person-years). After adjusting for potential confounders, poor control was independently associated with an increased risk of primary efficacy outcomes (aHR 2.30; 95% CI 1.22–4.32; p=0.01) and primary safety outcomes (aHR 1.59; 95% CI 1.18–2.14; p=0.01). Conclusion: Poor anticoagulation control (TTR < 65%) is strongly associated with an increased risk of both thromboembolic and hemorrhagic complications. Maintaining a TTR ≥ 65% remains a critical therapeutic target consistently linked to better clinical outcomes in real-world practice.