PB0003 - Time trends in vitamin K antagonist (VKA) treatment in the Netherlands in an era of transition to DOACs and lowering of VKA target intensity

Background: Direct oral anticoagulants (DOAC) were introduced in the Netherlands in the 2010s and vitamin K antagonist (VKA) target intensity was lowered (mainly from 2.5-3.5 to 2.0-3.0) in 2016.

Aims: To describe time trends (2013-2019) in patient characteristics, anticoagulation treatment quality, and clinical outcomes of VKA users in the Netherlands.

Methods: All VKA users with ≥1 international normalized ratio (INR) in a calendar year between 2013 and 2019 were identified from 17 Dutch anticoagulation clinics, constituting seven VKA-anticoagulated cohorts per year (2013-2019). Individuals of each cohort were followed from the first INR measurements in that year for one year. VKA treatment quality was evaluated by Time in Therapeutic Range (TTR). Risks of major bleeding, ischemic stroke/transient ischemic attack/systemic thromboembolism (IS/TIA/TE), myocardial infarction (MI), venous thromboembolism (VTE), and all-cause mortality were compared between years via multivariable Cox regression adjusting for demographic characteristics, antiplatelet drug use, and various comorbidities.

Results: The VKA users (n>100,000) were aging over years, with increasing prevalence of most comorbidities. TTR remained constant in 2013-2015 (median < 55%) but increased in 2016 and remained steady since then (median>65% in 2016-2019, Figure-1), while DOAC switching rate increased from 0.5% to 4.8%. One-year major bleeding risk increased since 2013 and peaked in 2015 (adjusted hazard ratio (aHR)=1.13, 95%CI 1.06-1.21, versus 2013), after which it began to decrease and plateaued (aHR=0.93, 95%CI 0.87-1.00, 2019 versus 2013). Risk of IS/TIA/TE, MI, VTE, and all-cause mortality were all increasing from 2013 to 2015, after which IS/TIA/TE and all-cause mortality risk kept increasing until reaching a plateau in 2017; MI risk remained constant, while VTE risk fluctuated (Figure-2).

Conclusion(s): VKA users in the Netherlands (2013-2019) were aging and increasingly switched to DOAC. VKA treatment quality improved after VKA target intensity was lowered in 2016, while major bleeding risk decreased, and risk of stroke/thromboembolism and all-cause mortality increased.