Fibrates May Impair Renal Function in Elderly Patients

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Many elderly patients who take fibrates for dyslipidemia experience a rise in serum creatinine level that in some leads to hospitalization, according to Canadian researchers.

In a population-based cohort study, Amit X. Garg, MD, PhD, of the London Health Sciences Centre in London, Ontario, and colleagues studied patients aged 66 years or older who received a new prescription for either a fibrate (19,072 patients) or ezetimibe (61,831 patients).

Dr. Garg's group chose ezetimibe as a comparator drug because, like fibrates, it is considered a second-line therapy after statins for treating dyslipidemia and it has no known acute renal effects. In randomized trials, fibrates have been shown to modestly raise serum creatinine levels. But many older patients and those with pre-existing chronic kidney disease were excluded from these trials.

This prompted the investigators to study fibrate use for such individuals to better understand the safety of this common medication in real practice. The results are published in the Annals of Internal Medicine (2012;156:560-569).

Compared with the ezetimibe patients, fibrate users were twice as likely to be hospitalized for an increase in serum creatinine levels and 30% more likely to consult a nephrologist.The two groups showed no difference in risk for all-cause mortality or receiving dialysis for severe acute kidney injury.

In a subpopulation of 1110 patients (220 on fibrates, 890 on ezetimibe), 9.1% of fibrate users had a rise in serum creatinine level of 50% or more compared with only 0.3% of ezetimibe users, which translated into a nearly 30-fold increased odds of a 50% or greater rise in serum creatinine level for the fibrate group.

In addition, compared with patients who did not have chronic kidney disease (CKD), those with CKD were three times more likely to be hospitalized for an increase in serum creatinine level after fibrate use.

“Until we have a better understanding of the underlying mechanism by which fibrates increase serum creatinine level and its long-term renal effects,” the authors concluded, “we believe that, when fibrates are prescribed to older patients, it would be prudent to start the prescription at a low dosage and arrange for close monitoring of renal function, as has been done in clinical trials. We believe this is especially true in elderly patients with existing chronic kidney disease.”

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