Pioglitazone Improved Endothelial Function
Diabetes medication seems to exhibit direct protective effects in the vasculature.
Treatment with the oral antidiabetic agent pioglitazone improved coronary endothelial function in patients with coronary artery disease. None of the participants in the prospective, placebo-controlled trial had diabetes.
“Six months’ treatment with pioglitazone (Actos, Takeda) at 30 mg daily was associated with a better coronary endothelial function compared with placebo in nondiabetic patients with coronary artery disease, independent of any significant metabolic effects,” said Jochen Wöhrle, MD, of the University of Ulm in Germany, during a presentation on Monday.
Parameters and endpoints
The percentage change in luminal
area — the study’s primary endpoint — favored those who underwent treatment with pioglitazone (Figure on pg. 3). During intracoronary baseline administration of acetylcholine while testing for coronary endothelial function, those in the pioglitazone arm had an average change in luminal area of –7.3% and –30.5% with dosages of 0.072 µg/min and 36 µg/min, respectively. At six-month follow-up, those dosages resulted in a –3.1% and –29.1% change in luminal area, respectively.
By comparison, patients in the placebo arm had a –5.9% and –38.2% change at baseline after receiving 0.072 µg/min and 36 µg/min dosages, respectively, of acetycholine, dosages which produced –12.0% and –43.3% average reductions at six months.
Collectively, the difference in the percentage change in luminal area between the two arms had a statistical significance of P < .0031.
The researchers observed no difference in total plaque volume between the two arms, the study’s secondary endpoint. After six months’ follow-up, there was no statistically significant difference between the pioglitazone- and placebo-treated patients in any of the metabolic parameters measured: fasting glucose and insulin, HbA1c, cholesterol, and triglycerides. Additionally, IVUS catheter data indicated statistically comparable measurements of vessel area, lumen area and plaque area for both groups.
“Our data bolster the hypothesis that the antidiabetic thiazolidinedione pioglitazone, in addition to its metabolic effects, exhibits direct protective effects in the vasculature,” said Wöhrle. “Larger clinical trials should replicate these findings and determine whether the effects of pioglitazone treatment on coronary endothelial function also translate into clinical benefits.”
Treating risk factors
“This study tests a very innovative idea, and while it is too small to change clinical practice, it nonetheless raises the need for prospective trials to look at how improving endothelial function will impact cardiovascular events,” said Amir Lerman, MD, of the Mayo Clinic in Rochester, Minn., during an accompanying critique.
In reviewing the results of Wöhrle and colleagues, Lerman cautioned the audience about relying on drug treatments when nonmedical treatments are needed.
“We need to be careful when we have a drug that affects cardiovascular health via medication, such as we have here,” Lerman said. “In many of these patients, including those in this trial, we need to first address their lifestyles and risk factors that have initially given them their cardiovascular problems.” 