New Fibrate Use and Acute Renal Outcomes in Elderly Adults

Abstract

Background: Fibric acid derivatives (fibrates) have been shown to increase serum creatinine level in randomized trials. Objective: To assess renal outcomes in elderly adults within 90 days of a new fibrate prescription. Design: Population-based cohort study. Setting: Ontario, Canada. Patients: Patients aged 66 years or older with a new outpatient prescription for a fibrate or ezetimibe (comparator drug) between January 2004 and December 2008. Measurements: Hospitalization for an increase in serum creatinine level (primary outcome) and consultation with a nephrologist, receipt of dialysis for severe acute kidney injury, all-cause mortality, and increases in serum creatinine level (secondary outcomes). All outcomes were assessed within 90 days of a new prescription for ezetimibe or a fibrate. Results: Compared with ezetimibe users (n = 61 831), fibrate users (n = 19 072) were more likely to be hospitalized for an increase in serum creatinine level (adjusted odds ratio, 2.4 [95% CI, 1.7 to 3.3]) and were more likely to consult a nephrologist (absolute risk difference, 0.15% [CI, 0.01% to 0.29%]; adjusted odds ratio, 1.3 [CI, 1.0 to 1.6]). There were no differences between groups in the risk for all-cause mortality or receiving dialysis for severe acute kidney injury. In a subpopulation of 1110 patients (fibrates, n = 220; ezetimibe, n = 890), 9.1% of fibrate users and 0.3% of ezetimibe users had an increase in serum creatinine level of 50% or more (absolute difference, 8.8% [CI, 4.5% to 13.1%]; odds ratio, 29.6 [CI, 8.7 to 100.5]). Risks were greater among fibrate users with chronic kidney disease. Limitations: Because hospitalizations for an increase in serum creatinine level were underestimated, absolute differences may be misleading. Most patients (91%) were prescribed fenofibrate. Serum creatinine levels were measured as part of routine care and were not available for everyone or at predefined times. Conclusion: New fibrate use in elderly adults was associated with an increase in serum creatinine level and a small 90-day absolute increase in hospitalizations and nephrologist consultations. There was no detectable effect on dialysis for severe acute kidney injury or on mortality. The mechanism and clinical significance of the increase in serum creatinine level with fibrates is unclear. Primary Funding Source: Ontario Ministry of Health and Long-Term Care Drug Innovation Fund.