Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduces circulating platelet activity in patients without diabetes mellitus who have coronary artery disease.
BACKGROUND
Rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, is used in the treatment of type 2 diabetes mellitus, and in vitro data has shown that it may have anti-platelet effects independent of its hypoglycemic effects. The aim of this study was to assess the effect of rosiglitazone on circulating platelet activity in patients without diabetes mellitus who had coronary artery disease.


METHODS
Ninety-two patients with stable, documented coronary artery disease without diabetes mellitus were studied. Patients were randomized (double-blind) to receive placebo or rosiglitazone for 12 weeks. Circulating platelet activity was measured at baseline and after 12 weeks of therapy with whole blood flow cytometry to quantify platelet P-selectin expression.


RESULTS
The percentage of P-selectin positive platelets was significantly reduced by rosiglitazone treatment compared with placebo (P =.04). In the rosiglitazone group, the percentage of P-selectin positive platelets (median with interquartile range) decreased from 0.1 % (0.05-0.24) to 0.05 % (0.01-0.15). Rosiglitazone treatment significantly reduced the insulin resistance index (HOMA-R) compared with placebo (P =.02). No significant correlation was observed between change in platelet activity and change in HOMA-R.


CONCLUSIONS
Rosiglitazone significantly reduces circulating platelet activity in patients without diabetes mellitus who have coronary artery disease. This effect appears to be independent of any insulin-sensitising effect.
Sidhu
Jagdip S
JS
Coronary Artery Disease Research Unit, Cardiological Sciences, St. George's Hospital Medical School, London, United Kingdom.
Cowan
Dahlia
D
Tooze
Jennifer A
JA
Kaski
Juan-Carlos
JC
D001792:Blood Platelets / Q000378:metabolism; D003327:Coronary Disease / Q000097:blood* / Q000150:complications; D048909:Diabetes Complications; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D010976:Platelet Count; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000819:agonists*
D019007:P-Selectin; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone