title: The cardiovascular effects of peroxisome proliferator-activated receptor agonists.
abstract: Although peroxisome proliferator-activated receptor agonists are prescribed to improve cardiovascular risk factors, their cardiovascular safety is controversial. We therefore reviewed the literature to identify landmark randomized controlled trials evaluating the effect of peroxisome proliferator-activated receptor gamma agonists (pioglitazone and rosiglitazone), alpha agonists (fenofibrate and gemfibrozil), and pan agonists (bezafibrate, muraglitazar, ragaglitazar, tesaglitazar, and aleglitazar) on cardiovascular outcomes. Pioglitazone may modestly reduce cardiovascular events but also may increase the risk of bladder cancer. Rosiglitazone increases the risk of myocardial infarction and has been withdrawn in European and restricted in the United States. Fibrates improve cardiovascular outcomes only in select subgroups: fenofibrate in diabetic patients with metabolic syndrome, gemfibrozil in patients with dyslipidemia, and bezafibrate in patients with diabetes or metabolic syndrome. The cardiovascular safety of the new pan agonist aleglitazar, currently in phase II trials, remains to be determined. The heterogenous effects of peroxisome proliferator-activated receptor agonists to date highlight the importance of postmarketing surveillance. The critical question of why peroxisome proliferator-activated receptor agonists seem to improve cardiovascular risk factors without significantly improving cardiovascular outcomes requires further investigation.
authors.affiliation: Division of Cardiology, Jewish General Hospital/McGill University, Montreal, Quebec, Canada.
authors.forename: Sayuri N
authors.initials: SN
authors.lastname: Friedland
authors.forename: Aaron
authors.initials: A
authors.lastname: Leong
authors.forename: Kristian B
authors.initials: KB
authors.lastname: Filion
authors.forename: Jacques
authors.initials: J
authors.lastname: Genest
authors.forename: Iliana C
authors.initials: IC
authors.lastname: Lega
authors.forename: Salvatore
authors.initials: S
authors.lastname: Mottillo
authors.forename: Paul
authors.initials: P
authors.lastname: Poirier
authors.forename: Jennifer
authors.initials: J
authors.lastname: Reoch
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Eisenberg
mesh_terms: D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002319:Cardiovascular System / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D047492:Peroxisome Proliferator-Activated Receptors / Q000009:adverse effects / Q000819:agonists / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D047492:Peroxisome Proliferator-Activated Receptors