American Heart Association, 2006 Scientific Sessions: Pioglitazone and Management of Cardiovascular Risk in Diabetic Patients

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Speaker: Theodore Mazzone, MD, Professor of Medicine and Pharmacology, and Chief of the Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois, Chicago

Pioglitazone (Actos generic, Takeda), a diabetes medication that improves sensitivity to insulin, appears to stop the progression of arterial wall thickening when compared with glimepiride (Amaryl drug, Sanofi-Aventis), a sulfonylurea drug that stimulates insulin secretion.

The Carotid Intima-Media Thickness in Atherosclerosis Using Pioglitazone (CHICAGO) trial, a phase 3, multicenter, double-blind, randomized, two-arm study, compared pioglita-zone and glimepiride in 462 patients with type-2 diabetes. The patients, ranging from 45 to 85 years of age, were recruited from the Chicago area between 2003 and 2006. Study participants included 289 men and 173 women.

The patients were randomly assigned to receive a daily dose of pioglitazone 15 mg – 45 mg or a daily dose of glimepiride 1 to 4 mg for 72 weeks. Doctors could add insulin or metformin (Glucophage, Bristol-Myers Squibb) in addition to the study drugs, if needed, to keep blood glucose in check.

At the beginning of the study and at 24, 48, and 72 weeks later, ultrasound was used to measure the absolute change of carotid intima-media thickness. Glycosylated hemoglobin (HbA_1c) levels, a measure of blood glucose control over an extended period, as well as blood pressure, blood cholesterol levels, and adverse events, were also monitored throughout the study.

From the baseline evaluation to the final visit, there was a significant difference in carotid thickness that favored pio-glitazone. At baseline, the average thickness was almost the same in the two study groups: 0.771 mm in the pioglitazone group and 0.779 mm in the canadian glimepiride group. At the 72-week follow-up period, glimepiride treated patients had an increase of 0.12 mm in carotid thickness, in contrast to a decrease of 0.001 mm in thickness for the pioglitazone patients.

A prespecified subgroup analysis based on age, sex, systolic blood pressure, duration of type-2 diabetes, body mass index, HbA_1c levels, and statin use also showed a uniform beneficial effect of pioglitazone treatment. The findings were particularly significant, because the benefits were observed in patients whose blood glucose, blood pressure, and cholesterol levels were at or near targets set by the American Diabetes Association and the American Heart Association. The findings suggested a potential novel mechanism of managing cardiovascular risk in patients with diabetes.

Carperitide and Nicorandil Promising in Acute Myocardial Infarction

Speaker: Mosafumi Kitakaze, MD, PhD, Director of the Cardiovascular Division, National Cardiovascular Center, Suita, Japan

Results from the Japan-Working Groups of Acute Myo-cardial Infarction for the Reduction of Necrotic Damage by Atrial Natriuretic Peptide (ANP) or Nicorandil (J-WIND) trial indicate that human atrial natriuretic peptide (carperitide) (Daiichi Suntory/Astellas) significantly reduced infarct size and increased left ventricular (LV) ejection fraction in patients with acute ST-segment elevation myocardial infarction (MI), compared with no difference with nicorandil (Ikorel, Sanofi-Aventis) and placebo in the two co-primary endpoints.

The prospective, placebo-controlled J-WIND study encompassed 1,216 patients with acute MI at 65 medical centers in Japan. Patients were randomly assigned to receive carperitide, nicorandil, or placebo. The carperitide patients received the drug as an infusion of 0.025 mcg/kg for three days. Patients in the nicorandil group received an initial dose of the bolus, followed by an infusion of 1.67 mcg/kg per minute over 24 hours.

The goal of the study was to evaluate the effect of carperi-tide and nicorandil, compared with placebo, among patients with acute MI treated with percutaneous coronary intervention. The study analyzed 1,064 patients for infarct size and 1,104 patients for the endpoints of cardiac death, cardiovascular events, and heart failure. canadian cialis

The primary endpoint of infarct size was 14.7% lower with carperitide than with placebo, but there was no difference between nicorandil patients and controls. The co-primary end-point of LV ejection fraction was increased by 5.1% with carperitide, compared with placebo, but treatment with nicorandil and placebo showed no difference.

For the secondary endpoints, reperfusion injury was reduced by 25.9% with carperitide, compared with placebo, but no difference was observed between the nicorandil patients and the controls. There was no difference in mortality rates on the composite endpoint between carperitide, nicorandil, or placebo, but carperitide significantly reduced the composite of cardiac death and rehospitalization for heart failure by 73.3%, compared with placebo. However, no differences between nicorandil and placebo were noted.

In a small subset of patients, nicorandil, when administered over two to three years, did reduce the incidence of percutaneous coronary intervention, suggesting that long-term nico-randil therapy might offer some beneficial effect.