American Journal of Cardiovascular Drugs

, Volume 10, Supplement 2, pp 10–17 | Cite as

Pleiotropic Effects of Statins

Evidence Against Benefits Beyond LDL-Cholesterol Lowering
  • Terje R. Pedersen
Review Article


3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are extremely effective at reducing low-density lipoprotein (LDL) cholesterol and have been demonstrated to reduce mortality and the risk of major cardiovascular events in a number of large primary and secondary prevention studies. The linear relationship between LDL-cholesterol and cardiovascular risk suggests statins work solely by reducing LDL-cholesterol, and that ancillary properties do not contribute to cardiovascular risk reduction. In recent years, however, a number of additional non-lipid-lowering, or ‘pleiotropic’, effects of statins have been suggested to contribute to their efficacy in cardiovascular disease. The first data to suggest that statins may have benefits beyond lipid lowering came from the Heart Protection Study, in which simvastatin reduced mortality and morbidity even in patients with ‘normal’ LDL-cholesterol levels (2.6 mmol/L or 100 mg/dL). It has since been demonstrated, however, that cardiovascular risk remains high at this LDL concentration, but is substantially reduced in those achieving levels below 2.0 mmol/L (77 mg/dL). Evidence for the pleiotropic effects of statins in heart failure comes largely from retrospective and subgroup analyses of large studies. When statin therapy is compared with placebo, or when high-dose statin therapy is compared with low-dose treatment, a lower incidence of heart failure or hospitalization is observed. Despite promising retrospective data, however, two prospective studies of rosuvastatin in the treatment of patients with New York Heart Association class II–IV heart failure showed no impact on the primary endpoint and only one of the studies showed a lower rate of hospitalization favouring rosuvastatin. A number of small studies has shown evidence for mechanisms of action of statins outside of LDL-cholesterol lowering, including improvements in endothelial function, halting or retardation of atheroma development, reduction in inflammation and antithrombotic effects. The linear relationship between LDL-cholesterol lowering and reduction in coronary heart disease risk, as well as a lack of conclusive evidence for other mechanisms of action raise the question of whether any cholesterol-lowering agent is equally effective for reducing cardiovascular risk, but recent data from the torcetrapib clinical trial programme suggest this is not the case. Future cholesterol-lowering modalities must be able to demonstrate efficacy and good tolerability in large-scale clinical trials.


Simvastatin Atorvastatin Rosuvastatin Torcetrapib Heart Protection Study 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author would like to acknowledge the assistance of Claire Byrne and Neil Reynolds of inScience Communications, a Wolters Kluwer business, who provided medical writing support funded by Pfizer. The author has acted as a consultant for Merck Sharpe & Dohme and has received honoraria for speaking from Merck Sharpe & Dohme, Astra- Zeneca and Pfizer.


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© Adis Data Information BV 2010

Authors and Affiliations

  1. 1.Centre for Preventive MedicineOslo University Hospital, Ullevål University of OsloOsloNorway

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