Cholesterol drug response unaffected by metabolic rates
MedWire News: Patients tend to achieve similar reductions in low-density lipoprotein (LDL) cholesterol whether treated with simvastatin or ezetimibe, a study shows.
The researchers found large inter-individual differences in the response to ezetimibe, which inhibits cholesterol absorption, and to simvastatin, which inhibits cholesterol synthesis. But the responses to these drugs were tightly correlated within individuals, regardless of their baseline rates of cholesterol synthesis and absorption.
“Thus, we found no evidence to support the use of a personalized medicine approach to select the optimal cholesterol-lowering medication for a patient based on indices of cholesterol metabolism,” say Helen Hobbs (University of Texas Southwestern Medical Center, Dallas, USA) and colleagues.
Hobbs et al randomly assigned 215 US men (43% African American) with elevated LDL cholesterol levels to receive placebo, ezetimibe (10 mg/day), simvastatin (10 mg/day), and both active drugs for 6 weeks each in a double-blind, crossover trial. Their findings appear in the Journal of Clinical Endocrinology & Metabolism.
The participants had an average baseline LDL cholesterol level of 146 mg/dl (3.77 mmol/l), which was reduced by 19%, 25%, and 41% with ezetimibe, simvastatin, and combined treatment, respectively.
Participants’ reductions in LDL cholesterol did not correlate with their baseline levels of campesterol and lathosterol (surrogate markers of cholesterol absorption and synthesis, respectively). There was also no association between LDL cholesterol reductions and levels of proprotein convertase subtilisin-like kexin type 9, which promotes LDL receptor degradation.
However, there was a strong, highly significant correlation between individual responses to simvastatin and ezetimibe. This suggests that “the major factors determining the magnitude of LDL cholesterol lowering on these agents are downstream of their primary sites of action,” comment Hobbs and team.
Also, the researchers found that plasma campesterol to lathosterol ratios fell almost as much in ezetimibe nonresponders as in responders, indicating that the primary action of the drug does not determine the overall response.
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By Eleanor McDermid