Effect of Pioglitazone on Platelet Aggregation in a Healthy Cohort

Background: Peroxisome proliferator-activated receptor (PPAR) agonists can favorably influence atheroma proliferation, lipoprotein metabolism and macrovascular complications. Pioglitazone, one of the thiazolidinedione compounds, is a PPAR ligand activator and a clinically important PPAR agonist. There is controversy in the literature about its potential antiplatelet effects. Its direct platelet inhibition is a novel hypothesis tested in animal models and in human populations with underlying diabetic and/or cardiovascular diseases. The present study was aimed to test the hypothesis of direct platelet aggregation inhibition with the use of pioglitazone in a healthy population.

Methods: This prospective study was started after obtaining institutional review board approval. The platelet aggregation response to adenosine diphosphate, epinephrine, collagen and arachidonic acid was measured in healthy subjects before and after treatment with pioglitazone. The fasting lipid profile including total cholesterol, low-density lipoprotein, very-low-density lipoprotein and high-density lipoprotein was also measured.

Results: Twenty subjects, 12 males and 8 females, were enrolled with a mean age of 31.5 ± 7.6 years (range 24-46). Two subjects did not complete the study and were excluded. The mean HbA1C was 5.4% (range 4.7-5.7). The study showed a non-significant platelet aggregation reduction after taking a 7-day pioglitazone course. The adenosine diphosphate-mediated platelet aggregation difference was not significant (p = 0.99); the arachidonic acid-mediated platelet aggregation difference was 0.6% (p = 0.93), for epinephrine 0.9% (p = 0.88) and for collagen 0.2% (p = 0.94). Further, it did not show a favorable response of lipoprotein profile with a non-significant reduction in all lipid panel values even though there is a slight reduction in total cholesterol, triglyceride, low-density lipoprotein and very low-density lipoprotein and a slight increase in high-density lipoprotein.

Conclusions: We conclude that pioglitazone does not have a direct platelet aggregation inhibition effect in a healthy population, nor does it have a favorable effect on lipoprotein profile after a short treatment period.