Prasugrel Exhibited Greater Antiplatelet Activity than High Dose Clopidogrel
in Type 2 Diabetes Patients with Coronary Artery Disease

TORONTO , Dec. 3 /CNW/ - Results from a new study showed patients with type 2 diabetes who also had coronary artery disease (CAD) experienced greater antiplatelet activity with the investigational antiplatelet drug prasugrel compared to Plavix(R) (clopidogrel). Patients who received a 60 mg loading dose and 10 mg maintenance dose of prasugrel achieved significantly greater platelet inhibition compared with a 600 mg loading dose and 150 mg maintenance dose of Plavix.(1) These data were presented at the American Heart Association 2009 Scientific Sessions in Orlando , Florida.

The OPTIMUS-3 (Third Optimising anti-Platelet Therapy In Diabetes MellitUS) study, which evaluated 35 patients with type 2 diabetes who also had CAD and were taking aspirin, showed that within four hours, the level of platelet inhibition as measured using the VerifyNow(R) P2Y12 Test with a 60 mg loading dose of prasugrel was higher than observed with a 600 mg loading dose of clopidogrel (89.3 per cent vs. 27.7 per cent inhibition of platelet activation (IPA), respectively; P(less than)0.0001).(1) In addition, one hour after the loading dose, patients who received prasugrel had 50 per cent IPA compared with 13 per cent in patients who received clopidogrel (P(less than)0.0001).(1) The level of platelet inhibition achieved for each drug at four hours was nearly unchanged over the following 24 hours.(1) A 600 mg loading dose of clopidogrel is not currently approved for use by Health Canada .

"Not only are people with diabetes more prone to coronary artery disease, but they also have higher platelet reactivity than people without diabetes, and as a result, may not respond as well to antiplatelet therapy," said Dr. Shaun Goodman , Co-Chair of the Canadian Heart Research Centre. "The results of this study are encouraging, as there is a clear need for antiplatelet therapy that provides greater platelet inhibition for patients with diabetes than the current standard of care."

The OPTIMUS-3 study also looked at the maintenance doses of prasugrel and clopidogrel. After seven days, results showed that a 10 mg maintenance dose of prasugrel achieved greater platelet inhibition than a 150 mg maintenance dose of clopidogrel (62 per cent vs. 44 per cent IPA, respectively; P(less than)0.0001).(1)

Dr. Goodman noted that, "these findings support our previously published finding that prasugrel was superior to clopidogrel in reducing the chances of having a second heart attack in more than 3,000 patients with diabetes participating in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial 38 (TRITON-TIMI 38)."

About OPTIMUS-3

OPTIMUS-3 (Third Optimising anti-Platelet Therapy In Diabetes MellitUS) evaluated the pharmacodynamic effects of prasugrel compared with clopidogrel in 35 patients with type 2 diabetes who also had CAD and were taking aspirin. The double-blind crossover study compared loading and maintenance doses of prasugrel (60 mg and 10 mg, respectively) with a 600 mg loading dose and a 150 mg maintenance dose of clopidogrel for one week, followed by a 14-day washout period before patients crossed over to receive the alternate study drug.

Measurements of platelet inhibition were taken at several time periods, including baseline, one hour, four hours and 24 hours post loading dose, as well as six to eight days post maintenance dose during each period of the study. Inhibition of platelet aggregation was measured using three separate methods: VerifyNow(R) P2Y12 assay, light transmission aggregometry, and phosphorylation of vasodilator stimulated phosphoprotein (VASP). Of note, the first two methods were recently demonstrated to be able to identify patients undergoing percutaneous coronary intervention (PCI) who are at higher risk for adverse clinical events over the course of one year.(2)

About Diabetes and Coronary Artery Disease

Coronary artery disease (CAD) is the chronic narrowing or hardening of the coronary arteries and is a condition linked to acute coronary syndrome (ACS). Over time, plaques build up in the arteries of patients with CAD. If a plaque ruptures and a clot forms in the artery, it may suddenly block blood supply to the heart, a condition known as ACS.(3) Outcome from ACS is worse for people with diabetes.(4)

CAD is a serious health concern and a major cause of death for people with diabetes. According to the Canadian Diabetes Association, diabetes increases the prevalence of CAD by two- to three-fold.(4) More than 75 per cent of people with diabetes will die from coronary and cerebrovascular events.(4)

About Prasugrel

Prasugrel helps keep blood platelets from clumping together and developing a blockage in an artery. Prasugrel is currently approved in the United States and the European Union, for the treatment of acute coronary syndromes being managed with percutaneous coronary intervention. Prasugrel is currently under review by Health Canada .

About Lilly

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis , Indiana, Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs. Eli Lilly Canada , headquartered in Toronto , Ontario, employs more than 500 people across the country. Additional information about Eli Lilly Canada can be found at www.lilly.ca.

    
    References

    1. Angiolillo, D. Comparison of the Effects of Prasugrel with
       Clopidogrel on Platelet Function in Coronary Artery Disease Patients
       with Type 2 Diabetes Mellitus - Third Optimizing anti-Platelet
       Therapy In diabetes MellitUS (OPTIMUS-3). Poster presentation at the
       American Heart Association Scientific Sessions 2009, Orlando, Florida.
       Presented November 15, 2009.
    2. Breet, NJ. First Prospective Comparison Between Platelet Function
       Tests in Prediction of Clinical Outcomes in 1100 Patients Undergoing
       Coronary Stent Placement: Do Point-of-Care Platelet Function Assays
       Predict Clinical Outcomes in Clopidogrel Pretreated Patients
       Undergoing Elective PCI (POPular Study). Abstract in 2009 Late-
       Breaking Clinical Trial/Science Abstracts From the AHA Scientific
       Sessions 2009, Circulation 2009;120:2152-61.
    3. Cleveland Clinic. Understanding Coronary Artery Disease. Available at:
      http://my.clevelandclinic.org/heart/disorders/cad/understandingcad.aspx
       Last accessed on October 29, 2009.
    4. Canadian Diabetes Association. Cardiovascular disease and diabetes:
       Key elements from the CDA 2008 Clinical Practice Guidelines. URL:
       http://www.diabetes.ca/documents/about-diabetes/Synopsis_Final.pdf.
       Accessed November 12, 2009.
    

For further information: Jennifer Gordon, Eli Lilly Canada Inc., [phone]; Laura Grice, MS&L, [phone]