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Reduced Renal Function and Proteinuria Are Associated with a Higher Stroke Rate in Patients with Atrial Fibrillation (the ATRIA study)

Lindsey R. Perez, Pharm.D. Candidate, The University of Texas at Austin
Reviewed by Henry I. Bussey, Pharm.D., FCCP, FAHA
April, 2009

Reference: Go AS, Fang MC, Udaltsova N, et al. Impact of proteinuria and glomerular filtration rate on risk of thromboembolism in atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Circulation. 2009;119;1363-1369.

Factors such as advanced age, hypertension, coronary heart disease, prior stroke, and diabetes are recognized risk factors for stroke in patients with atrial fibrillation. New data from a cohort of 13,535 patients (33,165 patient-years of data) indicate that a reduced creatinine clearance and/or proteinuria are associated with an increased risk of stroke in patients with non-valvular atrial fibrillation who were not receiving anticoagulation.

Kidney function was assessed by estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease equation, and the presence of proteinuria was measured by a urine dipstick. A thromboembolic event was identified as either a stroke or a peripheral thromboembolic event.

A total of 676 thromboembolic events were recorded (Table 1). Analysis indicates that the risk of a thromboembolic event is progressively increased with lower levels of eGFR, and proteinuria further increases the risk. After adjusting for known stroke risk factors, there was a 16% increased thromboembolic rate with eGFR 45-59 mL/min/1.73m2 and a 39% increased rate with eGFR <45 mL/min/1.73m2 compared to eGFR =60 mL/min/1.73m2. Proteinuria independently increased stroke risk by 54% after adjusting for known stroke risk factors. Although the eGFR was unknown in approximately 15% of patients, the extensive size of the cohort provides ample validation of the results.

Table 1: Thromboembolic rates per 100 person-years by eGFR level with or without proteinuria
eGFR (mL/min/1.73m2) Proteinuria No Proteinuria
>=60 3.06 1.41
45-59 3.93 2.46
<45 4.69 3.97

The ATRIA study indicates that reduced kidney function is an independent risk factor for stroke and other peripheral thromboembolic events in patients with atrial fibrillation. Knowledge of a patient's kidney function and the presence of proteinuria may assist clinicians in the decision of whether to initiate anticoagulation in a patient with atrial fibrillation.

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