Ongoing clinical trials of the pleiotropic effects of statins

Jean Davignon¹, Lawrence A Leiter²

¹Clinical Research Institute of Montreal, Montreal, QC, Canada; ²Division of Endocrinology and Metabolism, St Michael’s Hospital, Toronto, ON, Canada

Background: The multiple effects (ie, pleiotropic effects of statins) have received increasing recognition and may have clinical applicability across a broad range of cardiovascular and noncardiovascular conditions. Objective: To determine the relevance and significance of ongoing clinical trials of the pleiotropic effects of statins, focusing on nonlipid effects. Method: Ongoing trials were identified through personal communication, reports presented at scientific meetings (2000–2004), and queries made to AstraZeneca, Bristol-Myers Squibb Co, Merck & Co, Novartis, and Pfizer, manufacturers of the currently marketed statins. Published trials and other source material were identified through electronic searches on MEDLINE (1990–2003), abstract books, and references identified from bibliographies of pertinent articles. Eligible studies were the clinical trials of statins currently under way in which primary or secondary outcomes included the statins’ nonlipid (ie, pleiotropic) effect(s). Data were extracted and trial quality was assessed by the authors. Results: Of the 22 ongoing trials of the nonlipid effects of statins identified, 10 assessed inflammatory markers and plaque stabilization, 4 assessed oxidized low density lipoprotein/vascular oxidant stress, 3 assessed end-stage renal disease, 3 assessed fibrinogen/viscosity, 2 assessed endothelial function, 2 assessed acute coronary syndrome, 2 assessed aortic stenosis progression, and 1 each assessed hypertension, osteoporosis, ischemic burden, Alzheimer’s disease, multiple sclerosis, and stroke (outcomes often overlapped).

Conclusion: Given the excellent safety and tolerability of statins as a class, full exploration of their pleiotropic effects has the potential to provide additional benefits to many patients.

Keywords: atherosclerosis, cholesterol, clinical trials, endothelium, lipoproteins, metabolism, myocardial infarction, pharmacology, vasculature