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Published on: February 28, 2012
Time in Therapeutic Range and Outcomes After Warfarin Initiation in Newly Diagnosed Atrial Fibrillation Patients With
Karolina Szummer1,2, Alessandro Gasparini3, Staffan Eliasson4
1Department of Medicine, Karolinska Institutet, Stockholm, Sweden karolina.szummer@karolinska.se.
Insights
Patients with atrial fibrillation and kidney dysfunction on warfarin have poorer anticoagulation control. Maintaining optimal time-in-therapeutic range (TTR) reduces adverse events, regardless of kidney function.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Renal dysfunction's impact on warfarin anticoagulation in atrial fibrillation (AF) patients is unclear.
- The association between poor anticoagulation and adverse outcomes in this population requires investigation.
Purpose of the Study:
- To determine if renal dysfunction affects anticoagulation control in AF patients treated with warfarin.
- To assess if poor anticoagulation control in these patients increases the risk of adverse events.
Main Methods:
- Observational study of 7738 AF patients initiating warfarin in Stockholm (2006-2011).
- Estimated glomerular filtration rate (eGFR) calculated from serum creatinine.
- Time-in-therapeutic range (TTR) assessed via international normalized ratio (INR) over 2 years.
Main Results:
- Patients with eGFR <30 had approximately 10% lower TTR compared to those with normal renal function.
- Adverse events (intracranial hemorrhage, ischemic stroke, myocardial infarction, death) occurred in 4.0% of patients.
- TTR ≤75% was independently associated with higher adverse event risk (OR 1.84-2.09), irrespective of eGFR.
Conclusions:
- Severe chronic kidney disease (eGFR <30) in AF patients correlates with worse INR control on warfarin.
- Achieving optimal TTR (>75%) is linked to a reduced risk of adverse events, independent of renal function.
Background:
It is unknown whether renal dysfunction conveys poor anticoagulation control in warfarin-treated patients with atrial fibrillation and whether poor anticoagulation control associates with the risk of adverse outcomes in these patients.
Methods And Results:
This was an observational study from the Stockholm CREatinine Measurements (SCREAM) cohort including all newly diagnosed atrial fibrillation patients initiating treatment with warfarin (n=7738) in Stockholm, Sweden, between 2006 and 2011. Estimated glomerular filtration rate (eGFR; mL/min per 1.73 m2) was calculated from serum creatinine. Time-in-therapeutic range (TTR) was assessed from international normalized ratio (INR) measurements up to warfarin cessation, adverse event, or end of follow-up (2 years). Adverse events considered a composite of intracranial hemorrhage, ischemic stroke, myocardial infarction, or death. During median 254 days, TTR was 83%, based on median 21 INR measurements per patient. TTR was 70% among patients with eGFR <30, around 10% lower than in those with normal renal function. During observation, adverse events occurred in 4.0% of patients, and those with TTR ≤75% were at higher adverse event risk. This was independent of patient characteristics, comorbidities, number of INR tests, days exposed to warfarin, and, notably, independent of eGFR: adjusted odds ratio (OR) 1.84 (95% CI, 1.41-2.40) for TTR 75% to 60% and adjusted OR 2.09 (1.59-2.74) for TTR <60%. No interaction was observed between eGFR and TTR in association to adverse events (P=0.2).
Conclusion:
Severe chronic kidney disease (eGFR <30) patients with atrial fibrillation have worse INR control while on warfarin. An optimal TTR (>75%) is associated with lower risk of adverse events, independently of underlying renal function.
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