Temporal Trends in Patient Characteristics, Anticoagulation Treatment Quality, and Clinical Outcomes of Individuals Receiving Vitamin K Antagonists in the Netherlands (2014 Until–2022)

OBJECTIVES: To describe temporal trends in the clinical landscape of vitamin K antagonist (VKA) treatment in the Netherlands, after the introduction of a lower international normalized ratio (INR) target range in 2016 and direct oral anticoagulants. METHODS: Data from 17 Dutch anticoagulation clinics between 2014 and 2022 were individually linked to nationwide healthcare data. Prevalent VKA users were identified on January 1 of each year, forming nine annual cohorts. We assessed baseline patient characteristics, anticoagulation treatment quality (using time in/above/below therapeutic range [TTR/ATR/BTR]), and annual odds ratios of major bleeding and thromboembolism for each cohort. RESULTS: The number of patients treated with VKAs increased from 101 090 in 2014 to 121 916 in 2017, followed by a decline to 73 649 in 2022. Over time, cohorts were characterized by increasing age and a higher prevalence of comorbidities, with a doubling of kidney disease. After the introduction of the lower INR target range, mean BTR decreased (~30% in 2014 to ~15% in 2022), while mean TTR increased (~54% in 2014 to ~67% in 2022), with stable mean ATR. Across calendar years, the 1-year odds ratio of major bleeding decreased from 1.71% (95% CI 1.63-1.79) in 2014 to 1.52% (95% CI 1.44-1.61) in 2022, whereas the odds ratio of ischemic stroke/transient ischemic attack/systemic thromboembolism increased from 1.14% (95% CI 1.08-1.21) in 2014 to 1.32% (95% CI 1.24-1.40) in 2022. The 1-year odds ratio of mortality increased from 5.09 (95% CI 4.95-5.22) to 8.55 (95% CI 8.35-8.75), with an OR of 1.74 (95% CI 1.68-1.81). CONCLUSIONS: VKA users declined between 2014 and 2022. The remaining patients using VKA became older and more comorbid. During this period, INR target ranges were lowered, while temporal changes were observed with decreasing odds ratio of major bleeding and increasing odds ratio of thromboembolism and mortality. Vitamin K antagonists (VKAs) are blood thinners that require monitoring. Monitoring is performed by measuring an internationalized normalized ratio (INR) in blood. Based on the measured INR and the INR target range, the dose of the VKA can be adjusted. Patients using VKAs in the Netherlands are monitored by anticoagulant clinics with a frequency of at least every 6 weeks. New blood thinners (DOACs) were introduced with an advantage that these do not require regular monitoring. DOACs are first choice treatment for indications such as atrial fibrillation and venous thrombosis. However, some patients cannot use DOACs, for reasons such as a limited kidney or liver function or indications requiring VKAs. We aimed to describe if and how the VKA population changed over time. We found that the number of VKA patients declined. The patients that were treated with VKAs became older with more coexisting diseases. One of the diseases that increased most was kidney disease, which doubled in percentage (from approximately 5% to 10%). Over time the risk of bleeding decreased and the risk of thromboembolism increased.