Statin Adverse Events in Primary Prevention: Between Randomized Trials and Observational Studies

Am J Med Sci. 2015 Oct;350(4):330-7. doi: 10.1097/MAJ.0000000000000527.


Considerable debate exists regarding who might benefit from statins for primary prevention. Statins have wide pleotropic effects, which contribute to their efficacy in lowering cardiovascular disease but may also result in adverse events (AEs). Caveats in identifying AEs in randomized controlled trials (RCTs) include the lack of a standardized definition of statin-associated AEs, the differences in properties of different statins, the selectivity of RCTs in choosing their participants, the presence of high rate of nonadherence/withdrawal from trials and other concerns related to study design and conflict of interest. Caveats in identifying or overestimating AEs in observational studies include failure to identify baseline confounders, ascertainment bias, confounding by indication and healthy user bias. Statin use in observational studies may be a surrogate marker for higher socioeconomic standards, access to health care or use of other preventive services. Integrating evidence from both RCTs and observational studies is of paramount importance for appropriate patient-centered decision.

Publication types

  • Review

MeSH terms

  • Cardiology / methods
  • Cardiovascular Diseases / prevention & control*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Observational Studies as Topic
  • Patient Compliance
  • Practice Guidelines as Topic
  • Primary Prevention
  • Propensity Score
  • Randomized Controlled Trials as Topic
  • Research Design
  • United States


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors