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Published on: February 26, 2013
Renal function and outcomes in anticoagulated patients with non-valvular atrial fibrillation: the AMADEUS trial
Stavros Apostolakis1, Yuotao Guo, Deirdre A Lane
1University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, UK.
Insights
Patients with atrial fibrillation and impaired renal function (CrCl <60 mL/min) face doubled stroke risk and increased bleeding risk. Renal status significantly aids stroke prediction, even with existing scores.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Limited data exist on how renal function affects outcomes in atrial fibrillation (AF) patients.
- Renal impairment is a common comorbidity in AF patients, potentially influencing treatment efficacy and safety.
Purpose of the Study:
- To assess the impact of renal function on stroke, systemic embolism (SE), and major bleeding in anticoagulated AF patients.
- To evaluate if renal function status improves existing stroke risk prediction scores (CHADS2, CHA2DS2VASc).
Main Methods:
- Post hoc analysis of the AMADEUS multicentre, randomized trial comparing idraparinux with vitamin K antagonists.
- Patients were stratified by creatinine clearance (CrCl) levels.
- Outcomes included stroke/SE and major bleeding; statistical analyses involved c-indexes and net reclassification improvement (NRI).
Main Results:
- Patients with CrCl <60 mL/min had a significantly higher annual stroke/SE rate (2.2%) compared to those with CrCl >90 mL/min (0.6%).
- Renal impairment (CrCl <60 mL/min) was associated with a >2-fold increased risk of stroke/SE and a ~60% increased risk of major bleeding.
- Adding CrCl <60 mL/min to CHADS2 or CHA2DS2VASc scores did not improve discrimination (c-index) but significantly improved risk reclassification (NRI).
Conclusions:
- Renal impairment significantly increases stroke and major bleeding risks in anticoagulated AF patients.
- Renal function status is an important, independent predictor of adverse events in AF patients.
- Incorporating renal function into risk scores may enhance prediction accuracy for stroke in AF patients.
Aims:
Limited data are available on the impact of renal function on the outcome of patients with atrial fibrillation (AF).
Methods And Results:
AMADEUS was a multicentre, randomized, open-label non-inferiority study that compared fixed-dose idraparinux with conventional anticoagulation by dose-adjusted vitamin K antagonists. We performed a post hoc analysis to assess the impact of renal function on the outcomes of anticoagulated AF patients. The primary efficacy outcome was the composite of stroke/systemic embolism (SE). The principal safety outcome of this analysis was major bleeding. We calculated c-indexes, reflecting the ability for discriminating diseased vs. non-diseased patients, and the net reclassification improvement (NRI, an index of inferior/superior performance of risk estimation scores). Of 4576 patients, 45 strokes and 103 major bleeding events occurred following an average follow-up of 325 ± 164 days. Patients with CrCl >90 mL/min had an annual stroke/SE rate of 0.6% compared with 0.8% for those with CrCl 60-90 mL/min and 2.2% for those with CrCl <60 mL/min (P < 0.001 for linear association). After adjusting for stroke risk factors, patients with CrCl <60 mL/min had more than two-fold higher risk of stroke/SE and almost 60% higher risk of major bleeding compared with those with CrCl ≥60. In patients with the CHA2DS2VASc score 1-2, CrCl <60 mL/min was associated with eight-fold higher stroke risk. When added to the CHA2DS2VASc or CHADS2 scores, CrCl <60 mL/min did not improve the c-indexes for CHADS2 (P = 0.054) or CHA2DS2VASc (P = 0.63) but resulted in significant NRI (0.26, P = 0.02) in this anticoagulated trial cohort.
Conclusion:
Renal impairment (CrCl <60 mL/min) doubles the risk of stroke and increased the risk of major bleeding by almost 60% in anticoagulated patients with AF. Renal impairment was additive to stroke risk prediction scores based on a significant NRI, but no significant improvement in discrimination ability (based on c-indexes) for CHA2DS2VASc or CHADS2 was observed.
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