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Warfarin in atrial fibrillation patients with moderate chronic kidney disease
Robert G Hart1, Lesly A Pearce, Richard W Asinger
1Department of Neurology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. robert.hart@phri.ca
Insights
Adjusted-dose warfarin significantly lowers stroke risk in atrial fibrillation patients with stage 3 chronic kidney disease (CKD). This treatment is effective and safe, reducing events by 76% without increasing major hemorrhage.
Area of Science:
- Cardiology
- Nephrology
- Clinical Trials
Background:
- Atrial fibrillation (AF) patients with stage 3 chronic kidney disease (CKD) face unknown stroke risks.
- Warfarin dosing strategies for stroke prevention in this population are not well-established.
Purpose of the Study:
- To evaluate the efficacy of adjusted-dose warfarin in preventing stroke in AF patients with stage 3 CKD.
- To determine if CKD status independently impacts stroke risk in AF patients.
Main Methods:
- Analysis of patients with stage 3 CKD from the Stroke Prevention in Atrial Fibrillation III trials.
- Comparison of adjusted-dose warfarin (target INR 2-3) versus aspirin/low-dose warfarin in high-risk patients.
- Assessment of primary outcome: ischemic stroke or systemic embolism.
Main Results:
- 42% of trial participants had stage 3 CKD.
- Stage 3 CKD was associated with a doubled risk of primary events in patients not on adjusted-dose warfarin.
- Adjusted-dose warfarin reduced ischemic stroke/systemic embolism by 76% in high-risk AF patients with stage 3 CKD (P < 0.001).
- No significant difference in major hemorrhage rates was observed between treatment groups.
Conclusions:
- Stage 3 CKD is an independent risk factor for higher stroke rates in AF patients.
- Adjusted-dose warfarin is a highly effective treatment for reducing stroke and systemic embolism in high-risk AF patients with stage 3 CKD.
Background And Objectives:
The efficacy of adjusted-dose warfarin for prevention of stroke in atrial fibrillation patients with stage 3 chronic kidney disease (CKD) is unknown.
Design, Setting, Participants, & Measurements:
Patients with stage 3 CKD participating in the Stroke Prevention in Atrial Fibrillation 3 trials were assessed to determine the effect of warfarin anticoagulation on stroke and major hemorrhage, and whether CKD status independently contributed to stroke risk. High-risk participants (n = 1044) in the randomized trial were assigned to adjusted-dose warfarin (target international normalized ratio 2 to 3) versus aspirin (325 mg) plus fixed, low-dose warfarin (subsequently shown to be equivalent to aspirin alone). Low-risk participants (n = 892) all received 325 mg aspirin daily. The primary outcome was ischemic stroke (96%) or systemic embolism (4%).
Results:
Among the 1936 participants in the two trials, 42% (n = 805) had stage 3 CKD at entry. Considering the 1314 patients not assigned to adjusted-dose warfarin, the primary event rate was double among those with stage 3 CKD (hazard ratio 2.0, 95% CI 1.2, 3.3) versus those with a higher estimated GFR (eGFR). Among the 516 participants with stage 3 CKD included in the randomized trial, ischemic stroke/systemic embolism was reduced 76% (95% CI 42, 90; P < 0.001) by adjusted-dose warfarin compared with aspirin/low-dose warfarin; there was no difference in major hemorrhage (5 patients versus 6 patients, respectively).
Conclusions:
Among atrial fibrillation patients participating in the Stroke Prevention in Atrial Fibrillation III trials, stage 3 CKD was associated with higher rates of ischemic stroke/systemic embolism. Adjusted-dose warfarin markedly reduced ischemic stroke/systemic embolism in high-risk atrial fibrillation patients with stage 3 CKD.
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