New Fibrate Use and Acute Renal Outcomes in Elderly Adults: A Population-Based Study
What is the effect on renal outcomes in elderly adults within 90 days of a prescription for fibrates?
A population-based cohort study was conducted in Ontario, Canada. Patients were 66 years or older with a new outpatient prescription for a fibrate (predominantly fenofibrate) or ezetimibe (comparator drug) between January 2004 and December 2008. Outcomes included 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.
Mean age in both groups was 73 years. The fibrate group had 2% more with diabetes, 13% less coronary disease, similar renal function, and was less likely to be on angiotensin-converting enzyme inhibitor or angiotensin-receptor blockers. 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% confidence interval [CI], 1.7-3.3) and were more likely to consult a nephrologist (absolute risk difference, 0.15%; 95% CI, 0.01-0.29; adjusted odds ratio, 1.3; 95% CI, 1.0-1.6). 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 1,110 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%; 95% CI, 4.5-13.1; odds ratio, 29.6; 95% CI, 8.7-100.5). Risks were greater among fibrate users with chronic kidney disease.
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.
Large trials have shown no evidence that fibrates alone or in combination with statins reduce cardiovascular event (CVE) rates or total mortality, and may increase CVEs in diabetic women. This study and the evidence that fibrates increase venous thromboembolism support a conclusion that fibrates have a limited role, and should be used with caution.
Keywords: Fenofibrate, Azetidines, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Acute Kidney Injury, Canada, Venous Thromboembolism, Ontario, Creatinine, Hospitalization, Diabetes Mellitus
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