Key result
Statins provide no additional cardiovascular risk reduction beyond the degree of LDL-C lowering.
Why the study?
It is unclear whether the pleiotropic effects of statins contribute to cardiovascular risk reduction beyond that expected from LDL-C reduction alone.
Do statins reduce coronary heart disease and stroke risk more than non-statin interventions that achieve similar LDL-C reduction in participants of long-term randomized trials?
Meta-Analysis (n=81,859)
Placebo-controlled
Randomized
Do statins reduce coronary heart disease and stroke risk more than non-statin interventions that achieve similar LDL-C reduction in participants of long-term randomized trials?
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Although additional benefits can be demonstrated on surrogate endpoints such as endothelial function, the preponderance of evidence shows that even if present clinically, outcomes correlate strongly and linearly with LDL-C levels achieved irrespective of statin use.”
The cardiovascular benefits of statins are driven proportionately by the magnitude of LDL-C reduction, rather than independent pleiotropic effects.
OBJECTIVES: This study sought to determine whether statins reduce coronary heart disease (CHD) risk more than other interventions that also primarily lower low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Statins have anti-inflammatory, immunomodulatory, antithrombotic, vascular, and other non-LDL-C-lowering effects. It is unclear whether these pleiotropic effects contribute to cardiovascular risk reduction beyond that expected from LDL-C reduction alone. METHODS: Trials published in English language journals were retrieved by searching Medline (1966 to October 2004), bibliographies, and the author's reference files. Randomized, placebo-controlled trials of interventions to primarily lower LDL-C of three or more years' duration in which clinical disease or death were primary outcomes were used. Information on sample size, treatment type and duration, participant characteristics at baseline, reduction in lipids, and outcome was independently abstracted by two authors (J.R. and N.M.) using a standardized protocol. Data from 5 diet, 3 bile acid sequestrant, 1 surgery, and 10 statin trials, with 81,859 participants, were included in the CHD meta-regression analysis. RESULTS: The regression lines for non-statin and statin trials were similar and consistent with a one-to-one relationship between LDL-C lowering and CHD and stroke reduction over five years of treatment. CONCLUSIONS: The pleiotropic effects of statins do not seem to contribute an additional cardiovascular risk reduction benefit beyond that expected from the degree of LDL-C lowering observed in other trials that primarily lowered LDL-C.
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Robinson et al. (2005) conducted a meta-analysis in Coronary heart disease (n=81,859). Statins vs. Non-statin LDL-C lowering interventions (diet, bile acid sequestrants, surgery) was evaluated on Coronary heart disease and stroke reduction. Statin therapy did not provide additional cardiovascular risk reduction beyond that expected from the degree of LDL-C lowering observed with non-statin interventions over five years of treatment.
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