Adding ezetimibe to simvastatin was found to be safe in a pilot study of patients with chronic kidney disease, and the combined regimen decreased LDL cholesterol by approximately 40%, according to Martin Landray, Ph.D., of the University of Oxford (England) and his associates.
The 6-month study involved 203 patients treated for chronic kidney disease at eight British medical centers. One-fourth of the patients required dialysis. The mean age was 60 years. A total of 102 were randomly assigned to receive 20 mg simvastatin plus 10 mg ezetimibe daily, and the rest received simvastatin plus a placebo.
Both treatments significantly lowered LDL cholesterol levels at 1-, 3-, and 6-month follow-ups, but the addition of ezetimibe cut these levels a further 27% (21 mg/dL). The addition of ezetimibe also decreased total cholesterol levels by a further 16% and apolipoprotein B levels by a further 15% (Am. J. Kidney Dis. 2006;47:385–95).
These beneficial effects were noted in patients who required dialysis and in those who did not, although the study had limited power to assess possible differences between the two groups because of relatively small numbers of subjects, the investigators said.
Compliance with the combined therapy was similar to that with simvastatin monotherapy and approached 90% at 6 months. No serious adverse events were attributed to either treatment. There was no elevation of creatine kinase levels, and the drugs did not appear to affect blood calcium, phosphate, or retinol concentrations.
There was no excess risk with the combined therapy for gastrointestinal symptoms, although more patients taking ezetimibe reported having diarrhea. There also were no reports of myopathy. However, “the size and duration of this pilot study are insufficient to detect a moderate excess risk for serious myopathy or other safety outcomes reliably or [to] assess possible effects on major clinical events,” Dr. Landray and his associates noted.
These results suggest that combined therapy with simvastatin plus ezetimibe “is a potent yet well-tolerated cholesterol-lowering regimen,” they said. The researchers are now conducting a large-scale randomized trial examining the effects of lowering cholesterol on cardiovascular outcomes in patients with chronic kidney disease.