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Reduced Time in Therapeutic Range and Higher Mortality in Atrial Fibrillation Patients Taking Acenocoumarol
José Miguel Rivera-Caravaca1, Vanessa Roldán2, María Asunción Esteve-Pastor3
1Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom; Department of Hematology and Clinical Oncology, Hospital General Universitario Morales Meseguer, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain.
Purpose:
The efficacy and tolerability of vitamin K antagonists (VKAs) depends on the quality of anticoagulant control, reflected by the mean time in therapeutic range (TTR) of international normalized ratio 2.0 to 3.0. In the present study, we aimed to investigate the association between TTR and change in TTR (ΔTTR) with the risk of mortality and clinically significant events in a consecutive cohort of atrial fibrillation (AF) patients.
Methods:
We included 1361 AF patients stable on VKAs (international normalized ratio 2.0-3.0) during at least the previous 6 months. After 6 months of follow-up we recalculated TTR, calculated ΔTTR (ie, the difference between baseline and 6-month TTRs) and investigated the association of both with the risk of mortality and "clinically significant events" (defined as the composite of stroke or systemic embolism, major bleeding, acute coronary syndrome, acute heart failure, and all-cause deaths).
Findings:
The median ΔTTR at 6 months of entry was 20% (interquartile range 0-34%), 796 (58.5%) patients had a TTR reduction of at least 20%, while 330 (24.2%) had a TTR <65%. During follow-up, 34 (2.5% [4.16% per year]) patients died and 61 (4.5% [7.47% per year]) had a clinically significant event. Median ΔTTR was significantly higher in patients who died (35.5% vs 20%; P = 0.002) or sustained clinically significant events (28% vs 20%; P = 0.022). Based on Cox regression analyses, the overall risk of mortality at 6 months for each decrease point in TTR was 1.02 (95% CI, 1.01-1.04; P = 0.003), and the risk of clinically significant events was 1.01 (95% CI, 1.00-1.03; P = 0.028). Patients with TTR <65% at 6 months had higher risk of mortality (hazard ratio = 2.96; 95% CI, 1.51-5.81; P = 0.002) and clinically significant events (hazard ratio = 1.71; 95% CI, 1.01-2.88; P = 0.046).
Implications:
Our findings suggest that in AF patients anticoagulated with VKAs, a change in TTR over 6 months (ie, ΔTTR) is an independent risk factor for mortality and clinically significant events. Even in a cohort with good anticoagulation control, the risk for mortality and clinically significant events increases with every point deterioration of TTR.
Insights
Changes in time in therapeutic range (TTR) for atrial fibrillation (AF) patients on warfarin increase mortality risk. Even small TTR drops indicate higher risks for significant events and death.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Medicine
Background:
- Vitamin K antagonists (VKAs) efficacy relies on anticoagulation control, measured by time in therapeutic range (TTR).
- Suboptimal TTR increases risks for adverse events in patients with atrial fibrillation (AF).
Purpose of the Study:
- To investigate the association between TTR and change in TTR (ΔTTR) with mortality and clinically significant events in AF patients.
- To assess if ΔTTR is an independent risk factor for adverse outcomes in anticoagulated AF patients.
Main Methods:
- 1361 AF patients on VKAs with stable anticoagulation for at least 6 months were included.
- TTR was recalculated after 6 months, and ΔTTR was determined.
- Associations between TTR, ΔTTR, and a composite of mortality and major adverse events were analyzed using Cox regression.
Main Results:
- A median ΔTTR of 20% was observed; 58.5% of patients had a TTR reduction of at least 20%.
- Higher median ΔTTR was linked to increased mortality and clinically significant events.
- Each point decrease in TTR correlated with a 2% increase in mortality risk and a 1% increase in clinically significant event risk.
Conclusions:
- Change in TTR (ΔTTR) over 6 months is an independent risk factor for mortality and clinically significant events in AF patients on VKAs.
- Deterioration in TTR, even within a well-controlled cohort, elevates the risk of adverse outcomes.
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