A standard dose of prasugrel led to greater platelet inhibition and response profiles in type 2 diabetes mellitus and coronary artery disease (CAD) patients when compared with a double-dose of clopidogrel, according to the OPTIMUS-3 trial published online Jan. 20 in the European Heart Journal.
"Platelets from patients with DM [diabetes mellitus] demonstrate upregulation of several signaling pathways, which may explain the increased prevalence of low platelet inhibition following clopidogrel treatment and contribute to increased atherothrombotic risk in these patients compared with those without DM," the authors wrote.
Because comparisons of the effects of prasugrel and higher doses of clopidogrel have gone unexplored, Dominick J. Angiolillo, MD, of the University of Florida College of Medicine in Jacksonville, Fla., and colleagues aimed to compare these two drugs in 35 patients with type 2 diabetes and CAD between April 2008 and January 2009 in the OPTIMUS-3 (Optimizing anti-Platelet Therapy In diabetes MellitUS) trial .
Of the 35 patients, 18 received a 60 mg loading dose/10 mg maintenance dose of prasugrel (Effient, Eli Lilly/Daiichi Sankyo) and 17 received a 600 mg loading dose/150 mg maintenance dose of clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) during the first treatment period.
The researchers then assessed platelet function via the VerifyNow P2Y12 assay (Accumetrics) at zero, one, four and 24 hours and at seven days. Angiolillo and colleagues reported that patients administered prasugrel had greater inhibition of platelet aggregation (IPA) compared to those who were administered clopidogrel at four hours post-loading dose: 89.3 versus 27.7 percent.
After one week of maintenance dose therapy, IPA was still higher in patients administered prasugrel compared with clopidogrel: 61.8 versus 44.2 percent. However, the authors reported that differences between prasugrel and clopidogrel were significant at all time periods from one-hour post-loading dose to seven days when measured by the P2Y12 assay.
The researchers found that the rate of poor responders was zero to 3.1 percent for prasugrel and 35.3 to 82.9 percent for clopidogrel at the four-hour post-loading dose. At the 24-hour post-loading dose, there were no patients who were classified as poor responders to prasugrel but the range of poor responders for clopidogrel was 51.5 to 78.8 percent. These rates at seven days were 2.9 to 21.2 percent and 23.5 to 52.9 percent, respectively.
The researchers reported the rate of adverse events to be 14.7 percent for prasugrel and 25.7 percent for clopidogrel.
"Prasugrel also resulted in a better response profile with lower rates of poor responders after both the LD [loading dose] and MD [maintenance dose] periods, irrespective of platelet function assay or definition used. These findings may explain the clinical benefit observed with prasugrel in patients with DM," the authors concluded.
However, the authors said that because this was an exploratory analysis and not designed to examine rebound, the results should be interpreted with caution.