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Published on: November 10, 2017
Differential effects of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I
Michael H Davidson1, Leiv Ose, Jiri Frohlich
1Chicago Center for Clinical Research, Chicago, Illinois 60610, USA. mdavidson@protocare.com
Insights
Simvastatin demonstrated superior increases in high-density lipoprotein cholesterol (HDL-C) compared to atorvastatin at higher doses. This study highlights simvastatin
Area of Science:
- Cardiovascular pharmacology
- Lipid metabolism research
Background:
- Statins are prescribed to lower low-density lipoprotein cholesterol (LDL-C) and elevate high-density lipoprotein cholesterol (HDL-C).
- Previous research suggests simvastatin may be more effective than atorvastatin in raising HDL-C levels.
Purpose of the Study:
- To compare the effects of simvastatin and atorvastatin on HDL-C and apolipoprotein A-I (apo A-I) levels.
- To analyze these effects across various patient subgroups and drug dosages.
Main Methods:
- Analysis of three multicenter, randomized clinical trials comparing simvastatin and atorvastatin.
- Subgroup analyses included gender, age, baseline HDL-C, baseline LDL-C, and baseline triglycerides.
- Dosages ranged from 20-80 mg for simvastatin and 10-80 mg for atorvastatin.
Main Results:
- At higher doses (40 and 80 mg), simvastatin yielded significantly greater increases in HDL-C than atorvastatin (p < 0.05 to < 0.001).
- Simvastatin showed consistent HDL-C elevation across all doses, while atorvastatin exhibited a negative dose-response pattern.
- Atorvastatin also showed a negative dose-response for apo A-I, suggesting reduced HDL particle numbers at higher doses.
Conclusions:
- Simvastatin is more effective than atorvastatin in increasing HDL-C and apo A-I at higher doses in hypercholesterolemic patients.
- Atorvastatin demonstrated a dose-dependent decrease in HDL-C and apo A-I, unlike simvastatin.
- These differential effects were consistent across all patient subgroups analyzed.
Background:
In addition to lowering plasma levels of low-density lipoprotein cholesterol (LDL-C), statins also raise high-density lipoprotein cholesterol (HDL-C).
Hypothesis:
Recent studies have shown that treatment with simvastatin results in larger increases in HDL-C than those seen with atorvastatin. The results of three clinical studies are analyzed, comparing the effects of simvastatin and atorvastatin on HDL-C and apolipoprotein A-I (apo A-I) in the total cohort and in several subgroups of hypercholesterolemic patients. The three studies were all multicenter, randomized clinical trials that included simvastatin (20-80 mg) and atorvastatin (10-80 mg) treatment arms. The subgroup analyses performed were gender; age (< 65 and > or = 65 years); baseline HDL-C (male: < 40 or > or = 40 mg/dl; female: < 45 or > or = 45 mg/dl), baseline LDL-C (< 160 or > or = 160 mg/dl), and baseline triglycerides (< 200 or > or = 200 mg/dl).
Results:
Both drugs produced similar increases in HDL-C levels at low doses; however, at higher drug doses (40 and 80 mg), HDL-C showed a significantly greater increase with simvastatin than with atorvastatin (p < 0.05 to < 0.001). Therefore, while HDL-C remained consistently elevated across all doses of simvastatin, there appeared to be a pattern of decreasing HDL-C with an increasing dose of atorvastatin. A similar negative dose response pattern was also observed with apo A-I in atorvastatin-treated patients, suggesting a reduction in the number of circulating HDL particles at higher doses. Both drugs reduced LDL-C and triglycerides in a dose-dependent fashion, with atorvastatin showing slightly greater effects. The differential effects of atorvastatin and simvastatin on HDL-C and apo A-I were observed for both the whole study cohorts and all subgroups examined; thus, no consistent treatment-by-subgroup interactions were observed.
Conclusion:
The data presented show that, across different hypercholesterolemic patient subgroups, simvastatin increases HDL-C and apo A-I more than atorvastatin at higher doses, with evidence of a negative dose response effect on HDL-C and apo A-I with atorvastatin, but not simvastatin.
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