Peroxisome proliferator–activated receptor γ agonists for the Prevention of Adverse events following percutaneous coronary Revascularization—results of the PPAR Study

Bhatt, Deepak L.; Chew, Derek P.; Grines, Cindy; Mukherjee, Debabrata; Leesar, Massoud; Gilchrist, Ian C.; Corbelli, John C.; Blankenship, James C.; Eres, Avichai; Steinhubl, Steven; Tan, Walter A.; Resar, Jon R.; AlMahameed, Amjad; Abdel-Latif, Ahmed; Tang, H. Wilson; Brennan, Danielle; McErlean, Ellen; Hazen, Stanley L.; Topol, Eric J.

doi:10.1016/j.ahj.2007.03.029

« Previous Next »American Heart Journal
Volume 154, Issue 1 , Pages 137-143, July 2007

Peroxisome proliferator–activated receptor γ agonists for the Prevention of Adverse events following percutaneous coronary Revascularization—results of the PPAR Study

Deepak L. Bhatt, MD
- Cleveland Clinic, Cleveland, OH
- Reprint requests: Deepak L. Bhatt MD, FACC, FSCAI, FESC, FACP, Cleveland Clinic, Department of Cardiovascular Medicine, 9500 Euclid Avenue, Desk F25, Cleveland, OH 44195.
Derek P. Chew, MBBS, MPH
- Flinders Medical Centre, Adelaide, Australia
Cindy Grines, MD
- William Beaumont Hospital, Royal Oak, MI
Debabrata Mukherjee, MBBS
- University of Kentucky, Louisville, KY
Massoud Leesar, MD
- University of Louisville, Louisville, KY
Ian C. Gilchrist, MD
- Hershey Medical Center, Hershey, PA
John C. Corbelli, MD
- Millard Fillmore Hospital, Buffalo, NY
James C. Blankenship, MD
- Geisinger Medical Center, Danville, PA
Avichai Eres, MD
- Central Baptist Hospital, Lexington, KY
Steven Steinhubl, MD
- University of Kentucky, Louisville, KY
Walter A. Tan, MD, MS
- The University of North Carolina at Chapel Hill, Chapel Hill, NC
Jon R. Resar, MD
- Johns Hopkins Hospital, Baltimore, MD
Amjad AlMahameed, MD, MPH
- Cleveland Clinic, Cleveland, OH
Ahmed Abdel-Latif, MD
- Cleveland Clinic, Cleveland, OH
H. Wilson Tang, MD
- Cleveland Clinic, Cleveland, OH
Danielle Brennan, MS
- Cleveland Clinic, Cleveland, OH
Ellen McErlean, MSN, RN
- Cleveland Clinic, Cleveland, OH
Stanley L. Hazen, MD, PhD
- Cleveland Clinic, Cleveland, OH
Eric J. Topol, MD
- Case Western Reserve University, Cleveland, OH

Received 1 January 2007; accepted 19 March 2007. published online 01 May 2007.

Dr Bhatt reports having received honoraria for consulting on scientific advisory boards from Astra Zeneca, Bristol Myers Squibb, Cardax, Centocor, Daiichi-Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Millennium, Otsuka, Paringenix, PDL, Sanofi Aventis, Schering Plough, The Medicines Company, TNS Healthcare—all such honoraria are currently donated to nonprofit organizations. Dr Tang has served on the speakers' bureau for Takeda Pharmaceuticals and is a consultant to Amylin Pharmaceuticals, GlaxoSmithKline Pharmaceuticals, Philadelphia, PA, and F-Hoffman La Roche, Inc. The other authors did not report any disclosures.

Background

Patients with metabolic syndrome are at increased risk for cardiovascular complications. We sought to determine whether peroxisome proliferator–activated receptor gamma agonists had any beneficial effect on patients with metabolic syndrome undergoing percutaneous coronary intervention (PCI).

Methods

A total of 200 patients with metabolic syndrome undergoing PCI were randomized to rosiglitazone or placebo and followed for 1 year. Carotid intima-medial thickness (CIMT), inflammatory markers, lipid levels, brain natriuretic peptide, and clinical events were measured at baseline, 6 months, and 12 months.

Results

There was no significant difference in CIMT between the 2 groups. There was no difference in the 12-month composite end point of death, myocardial infarction (MI), stroke, or any recurrent ischemia (31.4% vs 30.2%, P = .99). The rate of death, MI, or stroke at 12 months was numerically lower in the rosiglitazone group (11.9% vs 6.4%, P = .19). There was a trend toward a greater decrease over time in high-sensitivity C-reactive protein values compared with baseline in the group randomized to rosiglitazone versus placebo both at 6 months (−35.4% vs −15.8%, P = .059) and 12 months (−40.0% vs −20.9%, P = .089) and higher change in high-density lipoprotein (+15.5% vs +4.1%, P = .05) and lower triglycerides (−13.9% vs +14.9%, P = .004) in the rosiglitazone arm. There was a trend toward less new onset diabetes in the rosiglitazone group (0% vs 3.3%, P = .081) and no episodes of symptomatic hypoglycemia. There was no excess of new onset of clinical heart failure in the rosiglitazone group, nor was there a significant change in brain natriuretic peptide levels.

Conclusions

Patients with metabolic syndrome presenting for PCI are at increased risk for subsequent cardiovascular events. Rosiglitazone for 12 months did not appear to affect CIMT in this population, although it did have beneficial effects on high-sensitivity C-reactive protein, high-density lipoprotein, and triglycerides. Further study of peroxisome proliferator–activated receptor agonism in patients with metabolic syndrome undergoing PCI may be warranted.