Ongoing clinical trials of the pleiotropic effects of statins.
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.


METHODS
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).


CONCLUSIONS
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.
Davignon
Jean
J
Clinical Research Institute of Montreal, Montreal, QC, Canada. davignj@ircm.qc.ca
Leiter
Lawrence A
LA
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D001018:Aortic Diseases / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D050197:Atherosclerosis / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D002986:Clinical Trials as Topic / Q000379:methods; D003251:Constriction, Pathologic / Q000188:drug therapy; D003704:Dementia / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy; D009103:Multiple Sclerosis / Q000188:drug therapy; D010024:Osteoporosis / Q000188:drug therapy; D012107:Research Design; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors