Mortality Data Presented for Patients Treated with Efient®/Effient® (Prasugrel) Who Underwent Isolated Coronary Artery Bypass Surgery

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Nov 16, 2010, 10:00 ET

CHICAGO, Nov. 16, 2010 /PRNewswire-FirstCall/ -- New results from an observational substudy from TRITON–TIMI 38 presented today at the American Heart Association (AHA) Scientific Sessions annual meeting showed that patients treated with Efient®/Effient® (prasugrel) prior to coronary artery bypass graft surgery (CABG) had a reduced overall mortality rate compared to patients treated with Plavix® (clopidogrel) (2.3 percent versus 8.7 percent respectively, p=0.016).(1)

This retrospective analysis involved 346 patients with acute coronary syndrome (ACS) who had received either study drug and subsequently underwent isolated CABG at some point during the 15-month TRITON-TIMI 38 trial.(2)

In addition to all-cause mortality, this same analysis found that the risk-adjusted rate of cardiovascular death at 30 days was also lower in patients treated with prasugrel compared with those receiving clopidogrel (0.6 percent versus 5.8 percent respectively, p=0.038).(3) Prasugrel-treated patients experienced a statistically significantly higher volume of chest tube blood loss at 12 hours post-CABG compared to the clopidogrel-treated patients (655 +/- 580 milliliters with Effient versus 503 +/- 378 milliliters with clopidogrel.(1)

"This analysis showed that prasugrel was associated with a significantly lower mortality rate compared with clopidogrel among these CABG patients but with a significantly higher risk of serious bleeding events," said Peter K. Smith, M.D., professor of surgery and division chief of Cardiovascular and Thoracic Surgery at Duke University Medical Center and lead investigator for the retrospective CABG analysis. "This analysis helps better define the risk of mortality for physicians who care for the ACS patients who may be targeted for PCI but end up undergoing CABG instead."

The prasugrel prescribing information includes a warning and precaution against starting prasugrel in patients likely to undergo urgent CABG surgery. The risk of bleeding is increased in patients receiving prasugrel who undergo CABG. If possible, prasugrel should be discontinued at least 7 days prior to CABG.(4)

Study Methodology

TRITON-TIMI 38 was a Phase III, randomized, double-blind, head-to-head clinical trial comparing the effects of prasugrel versus clopidogrel in patients with ACS who were managed with percutaneous coronary intervention (PCI), a procedure to open blockages in heart arteries, including the use of coronary stenting. The study enrolled 13,608 patients at 707 trial sites in 30 countries.

The primary endpoint of the study was the combined incidence of cardiovascular death, non-fatal heart attack or non-fatal stroke during at least 12 months following PCI. Patients were randomly assigned to one of two treatment groups and given a loading dose of either prasugrel 60 mg or the FDA-approved loading dose of clopidogrel 300 mg, followed by a daily maintenance dose of either prasugrel 10 mg or clopidogrel 75 mg. All patients also received a daily dose of aspirin (75 mg to 325 mg).(4,5)

This retrospective analysis included newly collected data on 346 patients who underwent isolated CABG following withdrawal of study drug, either prasugrel (n=173) or clopidogrel n=173), during the TRITON-TIMI 38 study.(2) Possible baseline imbalances between arms were adjusted using European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Society of Thoracic Surgeons (STS) scoring, two widely accepted and standardized methods of calculating cardiac operative mortality risk.(2) Bleeding was measured by chest tube blood loss, a standard methodused by surgeons.(2) Despite the adjustment for predicted risk of mortality at the time of CABG, this non-randomized comparison between prasugrel and clopidogrel may be subject to potential residual biases.(2)

About TRITON-TIMI 38 Results

In the overall TRITON-TIMI 38 trial, treatment with prasugrel produced a statistically significant 18 percent reduction in the relative risk of the combined measure of cardiovascular death, nonfatal heart attack or nonfatal stroke compared with clopidogrel in people with chest pain at rest or milder heart attacks (UA/NSTEMI) and a 21 percent reduction in the combined endpoint in people with more severe heart attacks (STEMI). In TRITON-TIMI 38, patients treated with prasugrel also experienced a 50 percent relative risk reduction in stent-related clots when compared with clopidogrel, regardless of stent type. Additionally, a retrospective analysis of TRITON-TIMI 38 showed that treatment with prasugrel resulted in a 26 percent reduction in the primary endpoint of cardiovascular death, myocardial infarction or stroke compared with clopidogrel among patients aged 75 years or younger who weighed at least 60 kg and had no known history of stroke or TIA.(6)

In the TRITON-TIMI 38 trial, the risk of non-coronary artery bypass graft (non-CABG) major bleeding, including fatal bleeding, was higher with prasugrel (2.2 percent incidence) compared with clopidogrel (1.7 percent incidence).(4,5) Compared with the overall study population, a higher risk of serious bleeding among prasugrel patients was most evident in three distinct patient populations that are readily identifiable: patients who weighed less than 60 kg, patients who were 75 years of age or older and patients who have had a prior transient ischemic attack (TIA) or stroke. A 5 mg maintenance dose is recommended for patients who weigh less than 60 kg. Prasugrel is generally not recommended for use in patients 75 years or older. If treatment is deemed necessary, a 5 mg dose of prasugrel may be used after careful risk-benefit evaluation. Patients with prior TIA or stroke should not be treated with prasugrel.

About Prasugrel

Daiichi Sankyo Company, Limited, and Eli Lilly and Company co-developed prasugrel, an oral antiplatelet agent discovered by Daiichi Sankyo and its Japanese research partner, Ube Industries, Ltd. Prasugrel helps keep blood platelets from clumping together and developing a blockage in an artery. The European Commission granted marketing authorization for prasugrel for the prevention of atherothrombotic events in patients with ACS undergoing PCI in 2009. Worldwide prasugrel has been approved in more than 65 countries.

About Acute Coronary Syndromes

Acute coronary syndrome includes heart attacks and unstable angina (chest pain). Coronary heart disease, which can result in ACS, is the single most common cause of death in the European Union, accounting for more than 741,000 deaths in the EU each year.(7) In addition, ACS affects nearly 1.5 million people in the United States annually.(8) Heart attack is a major manifestation of coronary heart disease, which occurs when the arteries become narrowed or clogged by cholesterol and fat deposits. In some cases the plaque can rupture, resulting in a blood clot, which may partially or totally block the blood supply to portions of the heart, resulting in ACS.(9) Many ACS patients undergo PCI to re-open the artery, which usually includes a stent placement.

About Daiichi Sankyo

The Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical products to address the diversified, unmet medical needs of patients in both mature and emerging markets. While maintaining its portfolio of marketed pharmaceuticals for hypertension, hyperlipidemia, and bacterial infections, the Group is engaged in the development of treatments for thrombotic disorders and focused on the discovery of novel oncology and cardiovascular-metabolic therapies. Furthermore, the Daiichi Sankyo Group has created a "Hybrid Business Model," which will respond to market and customer diversity and optimize growth opportunities across the value chain. For more information, please visit www.daiichisankyo.com

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers – through medicines and information – for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.

This press release contains certain forward-looking statements about prasugrel for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndromes who are managed with percutaneous coronary intervention and reflects Daiichi Sankyo's and Lilly's current beliefs. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. There is no guarantee that future study results and patient experience will be consistent with study findings to date or that the product will be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's filing with the United States Securities and Exchange Commission and Daiichi Sankyo's filings with the Tokyo Stock Exchange. Daiichi Sankyo and Lilly undertake no duty to update forward-looking statements.

Efient®/Effient® is a registered trademark of Eli Lilly and Company.

Plavix® is a registered trademark of Sanofi-Aventis Corp.

P-LLY

(1) Smith PK, Despotis GJ, Goodnough LT, Levy, J, Poston, R, Short, M, et al. Mortality benefit with prasugrel in TRITON-TIMI 38 coronary artery bypass grafting (CABG) cohort: Risk adjusted retrospective data analysis. Abstract presented at: 2010 American Heart Association Scientific Sessions; November 2010; Chicago, IL.

(2) Smith PK, Despotis GJ, Goodnough LT, Levy, J, Poston, R, Short, M, et al. Mortality benefit with prasugrel in TRITON-TIMI 38 coronary artery bypass grafting (CABG) cohort: Risk adjusted retrospective data analysis. Study presented at: 2010 American Heart Association Scientific Sessions; November 2010; Chicago, IL.

(3) Data on File at Eli Lilly and Company. Coronary Artery Bypass Grafting Cardiovascular Death Data Table.

(4) European Medicines Agency. Summary of Product Characteristics.

(5 Wiviott SD, Braunwald E, McCabe CH et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. New England Journal of Medicine. 2007:357(20);2001-2015.

(6) Wiviott S, Antman E and Braunwald. New Drugs and Technologies: Prasugrel. DOI: 10.1161 Circulation AHA.109.921502 p394-403.

(7) British Heart Foundation Health Promotion Research Group. European Cardiovascular Disease Statistics 2008. Updated 2008. Accessed November 4, 2010.

(8) American Heart Association. Heart Disease and Stroke Statistics – 2008 Update. Dallas, TX. American Heart Association. (Pg. 14).

(9) WebMD Medical Reference in Collaboration with the Cleveland Clinic. Heart Disease: Coronary Artery Disease. Accessed March 5, 2010.

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SOURCE Eli Lilly and Company