Prevention of In-Stent Neointimal Proliferation by Pioglitazone Study - POPPS

Description:

The goal of the trial was to evaluate treatment with pioglitazone compared with control among patients with type 2 diabetes.

Hypothesis:

Pioglitazone would be more effective in preventing restenosis and target lesion revascularization (TLR) after percutaneous coronary intervention (PCI).

Study Design

  • Randomized
  • Parallel

Patients Enrolled: 97
Mean Follow Up: 12 months
Mean Patient Age: 64 years
Female: 17%

Patient Populations:

  • Patients with type 2 diabetes and symptomatic heart disease, ranging from stable angina to ST-elevation myocardial infarction

Exclusions:

  • End-stage disease
  • Cardiogenic shock or congestive heart failure
  • Contraindication to antiplatelet therapy
  • Patients already taking pioglitazone
  • History of gastrointestinal bleeding
  • History of transient ischemic attack
  • Ineligible for coronary revascularization

Primary Endpoints:

  • Angiographic restenosis
  • TLR

Secondary Endpoints:

  • Death
  • Myocardial infarction
  • Major adverse cardiac events

Drug/Procedures Used:

Patients with type 2 diabetes mellitus undergoing PCI with bare-metal stents were randomized to pioglitazone (n = 48) versus control (n = 49).

Concomitant Medications:

There was no difference between the groups in medication use at follow-up. The use of aspirin was 100%, ticlopidine 83%, cilostazol 17%, beta-blocker 38%, angiotensin-converting enzyme inhibitor 38%, statin 65%, and sulfonylurea 42%.

Principal Findings:

Overall, 97 patients were randomized. The mean age was 64 years, 17% were women, and 24% presented with an acute myocardial infarction. The mean stent diameter was 3.5 mm and stent length was 17 mm.

In the pioglitazone group at follow-up, glycated hemoglobin was 6.8%, high-density lipoprotein cholesterol (HDL-C) was 49 mg/dl, and low-density lipoprotein cholesterol (LDL-C) was 111 mg/dl. In the control group at follow-up, glycated hemoglobin was 6.5%, HDL-C was 48 mg/dl, and LDL-C was 107 mg/dl.

The incidence of the primary outcome, angiographic restenosis at 6 months, was 17.4% with pioglitazone versus 35.0% with control (p = 0.06). The incidence of the coprimary outcome, TLR, was 13% versus 29.8% (p = 0.04), respectively.

At 12 months, death was 2% versus 6% (p = 0.29), myocardial infarction was 2% versus 2% (p = 0.99), TLR was 12.5% versus 31.9% (p = 0.02), and major adverse cardiac events were 14.6% versus 36.2% (p = 0.01), respectively for pioglitazone versus control.

Congestive heart failure was 2% versus 4% (p = NS) and peripheral edema was 4% versus 0% (p = NS), respectively.

Interpretation:

Among patients with type 2 diabetes undergoing PCI, pioglitazone marginally reduced binary restenosis at 6 months and significantly reduced TLR at 6 and 12 months. Although glycated hemoglobin decreased within both groups from baseline, there was no difference in this value between the groups. Death and myocardial infarction were similar between the groups. Major adverse cardiac events were significantly reduced with pioglitazone, which was driven by a reduction in TLR.

Limitations of this study include small sample size, limited follow-up, and open-label design. An appropriately powered double-blind trial on the topic is warranted.

References:

Takagi T, Okura H, Kobayashi Y, et al. A prospective, multicenter, randomized trial to assess efficacy of pioglitazone on in-stent neointimal suppression in type 2 diabetes: POPPS (Prevention of In-Stent Neointimal Proliferation by Pioglitazone Study). JACC Intv 2009;2:524-31.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Lipid Metabolism, Nonstatins, Acute Heart Failure, Chronic Angina

Keywords: Myocardial Infarction, Follow-Up Studies, Cholesterol, LDL, Angina, Stable, Diabetes Mellitus, Type 2, Edema, Percutaneous Coronary Intervention, Stents, Lipoproteins, LDL, Hemoglobin A, Glycosylated, Metals, Heart Failure, Cholesterol, HDL, Hypoglycemic Agents, Lipoproteins, HDL, Thiazolidinediones


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