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Should We Use PPAR Agonists to Reduce Cardiovascular Risk?
Journal article   Open access   Peer reviewed

Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

Jennifer G Robinson
PPAR research, Vol.2008, pp.891425-13
2008
DOI: 10.1155/2008/891425
PMCID: PMC2234387
PMID: 18288293
url
https://doi.org/10.1155/2008/891425View
Published (Version of record) Open Access

Abstract

Trials of peroxisome proliferator-activated receptor (PPAR) agonists have shown mixed results for cardiovascular prevention. Fibrates are PPAR- α agonists that act primarily to improve dyslipidemia. Based on low- and high-density lipoprotein cholesterol (LDL and HDL) effects, gemfibrozil may be of greater cardiovascular benefit than expected, fenofibrate performed about as expected, and bezafibrate performed worse than expected. Increases in both cardiovascular and noncardiovascular serious adverse events have been observed with some fibrates. Thiazolidinediones (TZDs) are PPAR- γ agonists used to improve impaired glucose metabolism but also influence lipids. Pioglitazone reduces atherosclerotic events in diabetic subjects, but has no net cardiovascular benefit due to increased congestive heart failure risk. Rosiglitazone may increase the risk of atherosclerotic events, and has a net harmful effect on the cardiovascular system when congestive heart failure is included. The primary benefit of TZDs appears to be the prevention of diabetic microvascular complications. Dual PPAR- α / γ agonists have had unacceptable adverse effects but more selective agents are in development. PPAR- δ and pan-agonists are also in development. It will be imperative to prove that future PPAR agonists not only prevent atherosclerotic events but also result in a net reduction on total cardiovascular events without significant noncardiovascular adverse effects with long-term use.
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