The Pharmaceutical Journal
Vol 269 No 7215 p355
14 September 2002

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European Society of Cardiology (www.escardio.org)

Diabetes drug shows anti-platelet activity in non-diabetic CHD patients

ROSIGLITAZONE (Avandia) could decrease the risk of atherothrombotic events in non-diabetic patients with coronary heart disease (CHD), British researchers have suggested.

They found that circulating platelet activity was halved in patients with CHD, but without diabetes, following treatment with the thiazolidinedione drug rosiglitazone.

Research fellow Dr Jagdip Sidhu and colleagues from St George's Hospital Medical School, London, randomised 92 non-diabetic CHD patients to receive rosiglitazone (4mg daily for eight weeks, then 8mg daily for four weeks) or placebo, in addition to their existing CHD therapies. They measured the number of platelets expressing P-selectin, which mediates platelet binding to leucocytes, and found that this decreased from a median of 0.1 to 0.05 per cent (P=0.04) in patients who had been treated with rosiglitzone. Levels of P-selectin expressing platelets in the placebo group remained at 0.1 per cent throughout the study. Rosiglitazone treatment also decreased insulin resistance compared with placebo, but the researchers say that the decrease in platelet activity was independent of any insulin-sensitising or glucose-lowering effect. Dr Sidhu explained: "If you lower glucose, you lower platelet activation. But we found the decrease in platelet activation was independent of rosiglitazone's effect on glucose — it may also have direct anti-platelet effects."

However, Dr Sidhu added that further research was needed to determine whether this reduction in platelet activity would translate into a tangible clinical benefit, namely a reduction in atherothrombotic events. He said: "We know that people with coronary artery disease have a higher P-selectin level than healthy people, so there is evidence to suggest it may be one important factor in the expression of the disease.

"But we are not yet advocating that this is a significant indication to use rosiglitazone for people who have coronary artery disease alone."

The research team is currently investigating the effect of rosiglitazone on other markers of platelet activation, such as platelet factor IV, in serum samples taken from these patients.

The data were presented at the European Society of Cardiology congress in Berlin earlier this month.