Uppsala, Sweden - Results of a phase 2 trial suggests that the new thienopyridine antiplatelet drug prasugrel (Lilly/Sankyo) may be more effective than clopidogrel, with a greater inhibition of platelet aggregation and fewer nonresponders.

The study, published online in the European Heart Journal on April 18, 2006, was conducted by a group led by Drs Tomas Jernberg and Lars Wallentin (University Hospital, Uppsala, Sweden).

Wallentin commented to heartwire: "As well as giving greater inhibition of platelets than clopidogrel, prasugrel appears to bring about this effect more rapidly, which is very important for acute situations. For example, in ACS patients undergoing urgent PCI, clopidogrel has to be given several hours beforehand to get the maximal effect, whereas prasugrel just needs 15 to 30 minutes. That's a big advantage."

Wallentin also pointed out that prasugrel does not seem to have the same variability of effect as seen with clopidogrel. "With clopidogrel, there are about 30% to 40% of patients who do not get adequate platelet inhibition. But we did not see this with prasugrel, which showed consistent stable platelet inhibition—higher than that seen with clopidogrel."

Noting that there is always a balance between efficacy and safety, Wallentin added that the safety data from this trial, although only preliminary, did look promising. "This was a dose-finding trial and involved only 100 patients treated for one month, and obviously longer-term data are needed, but our results suggest that with a loading dose of 60 mg and a maintenance dose of 10 mg daily, prasugrel gives more pronounced platelet inhibition than clopidogrel, without increasing bleeding risk," he said.

This is the dose that is now being studied in a large-scale phase 3 trial, TRITON-TIMI-38. This trial is comparing one year of treatment with prasugrel or clopidogrel in ACS patients taken to PCI. Another similar drug that will also be a competitor to clopidogrel is being developed by AstraZeneca and is also currently in phase 3 trials. It is being compared with clopidogrel in ACS patients in the PLATO trial.

In the current study, 100 stable coronary artery disease patients already taking aspirin were randomized to various different loading (day 1)/maintenance (days 2-28) doses of prasugrel or the approved 300-mg loading dose and 75-mg maintenance dose of clopidogrel. Doses of prasugrel tested were 40 mg/5 mg; 40 mg/7.5 mg; 60 mg/10 mg; and 60 mg/15 mg. Platelet aggregation was measured at multiple time points during the study.

Results showed that four hours after dosing, both loading doses of prasugrel achieved significantly higher levels of platelet inhibition than clopidogrel, with fewer nonresponders.

Results at the end of the study showed that the 10-mg and 15-mg maintenance doses of prasugrel achieved consistently higher inhibition of platelet aggregation than clopidogrel 75 mg, again with fewer nonresponders.

The researchers report that there were no major bleeding events in the study, and the number of bruising and minor bleeding events was similar in the three lower prasugrel maintenance-dose groups and the clopidogrel group. In the highest prasugrel-maintenance dose group (15 mg), there was a trend toward an increase in minor bruising and minor bleeding events.