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

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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.

Section snippets

Methods

PPAR was a randomized, multicenter, double-blind, two-arm pilot study comparing the effects of rosiglitazone maleate (4 mg BID orally) before and after PCI in patients with obesity and hypertension, dyslipidemia, or glucose intolerance when compared to placebo. Between January 2002 and August 2003, a total of 200 patients from 10 centers were randomized from the population of patients undergoing diagnostic angiography followed by PCI and in those in whom coronary anatomy was known and PCI was

Results

The baseline demographics of the placebo and rosiglitazone groups are listed in Table I, and the procedural characteristics are listed in Table II. Concomitant baseline medications are listed in Table III. Of note, there was a very high usage of lipid-lowering therapy.

There was no significant difference in CIMT progression rates or maximum/mean CIMT at 6 or 12 months in the rosiglitazone group compared with the placebo group, although 85 patients did not have evaluable data (Table IV). There

Discussion

This study has found a high rate of cardiovascular complications in patients with metabolic syndrome who present for PCI. The cumulative rate of death, MI, stroke, rehospitalization for recurrent ischemia or repeat target vessel revascularization was over 30% by 1-year follow-up in this population, illustrating the high-risk nature of patients with metabolic syndrome. While drug-eluting stents may be expected to reduce the rate of target vessel revascularization, other approaches will be

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  • Cited by (0)

    This study was funded by GlaxoSmithKline.

    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.

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