New ESC Guidelines Recommend Efient® (Prasugrel) as First-line Antiplatelet Therapy for Patients with Non-ST Segment Myocardial Infarction and Unstable Angina Acute Coronary Syndromes

PARIS, August 31, 2011 /PRNewswire/ --

In new guidelines from the European Society of Cardiology (ESC), prasugrel - a once daily oral antiplatelet medicine - received a Class I recommendation (level of evidence B)  for use in patients undergoing percutaneous coronary intervention (PCI) after experiencing a non-ST-segment elevation acute coronary syndrome (which comprises non-ST segment elevation myocardial infarction or NSTEMI - a type of heart attack - and unstable angina or UA)(1).  The highest available recommendation, Class I recognizes that prasugrel is considered a "beneficial, useful and effective" treatment option for first line use in these patients(1).

The Guidelines Committee endorsed the use of prasugrel in UA/NSTEMI patients (especially those with diabetes) who are clopidogrel naïve in whom coronary anatomy is known and who are proceeding to PCI(1).  The guidelineswere presented at the ESC Congress 2011 in Paris and are published in the European Heart Journal(1).

"UA and NSTEMI patients are at high risk of cardiovascular events, and they often represent a challenge in clinical practice. There is a significant body of evidence which showed that prasugrel can form part of an appropriate management strategy to minimize risk for these patients," said Professor Gilles Montalescot, Head of the Cardiac Care Unit at Pitie-Salpetriere Hospital, Paris, France. "The guidelines, based on the latest clinical evidence, set out clear recommendations that offer alternative treatment options, such as prasugrel, for treating some of these high risk patients."

In the updated guidelines - entitled Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation - prasugrel was recommended regardless of a patient's genetic status(1), and the guidelines state prasugrel does not appear to be affected by CYP inhibitors, including proton pump inhibitors(2).

NSTEMI and UA accounts for about 2.5 million hospital admissions worldwide(3). In Western countries, NSTE-ACS (NSTEMI and UA) is the most frequent type of ACS and represents the largest group of patients undergoing PCI. Despite advances in medical and interventional treatments, the mortality and morbidity remain high and equivalent to that of patients with severe heart attacks (known as STEMI) after the initial month(4). However, patients with NSTE-ACS constitute a heterogeneous group of patients with a highly variable prognosis. Therefore, early risk stratification is essential for selection of medical as well as interventional treatment strategies(4).

This new recommendation is based on the clinical evidence for prasugrel in UA/NSTEMI patient population in the TRITON-TIMI 38 study, which led to a level of evidence 'B' ('data derived from a single randomized clinical trial')(1). In the TRITON-TIMI 38 study, which included 10,074 patients withchest pain at rest (UA) or experiencing NSTEMI (74 percent of the study population), treatment with prasugrel produced a statistically significant 18 percent reduction in the relative risk of the combined endpoint of cardiovascular death, nonfatal heart attack or nonfatal stroke compared with clopidogrel(5). In this patient population, the incidence of non-CABG-related TIMI major (including life threatening and fatal), (2.2 percent with prasugrel vs. 1.6 percent with clopidogrel) and minor (2.3 percent with prasugrel and 1.6 percent with clopidogrel) bleeding was statistically significantly higher in patients treated with prasugrel compared to clopidogrel(6).

The publication of the guidelines comes just a few months after the addition of prasugrel to the joint American Heart Association (AHA), American College of Cardiology (ACC) and the Society for Cardiovascular Angiography and Interventions (SCAI) clinical practice guidelines in the United States, in which it was granted a Class 1B recommendation in UA/NSTEMI patients(7).

Granted marketing authorization by the European Commission in February 2009, prasugrel, co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in patients with ACS undergoing primary or delayed PCI.

About TRITON-TIMI 38

In the TRITON-TIMI 38 trial of 13,608 patients with ACS undergoing PCI, treatment with prasugrel produced a statistically significant 19 percent (P<0.001) reduction in the relative risk of the combined endpoint of cardiovascular death, nonfatal heart attack or nonfatal stroke compared with clopidogrel. This was driven primarily by a reduction in heart attack(5).

In the TRITON-TIMI 38 clinical trial, the incidence of non-coronary artery bypass graft (non-CABG) TIMI major bleeding, including fatal bleeding, was higher with prasugrel (2.2 percent incidence) compared with clopidogrel (1.7 percent incidence)(6). 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 with a prior history of 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 after careful individual benefit/risk evaluation, a 5 mg maintenance dose of prasugrel should be used (following a 60 mg loading dose). Patients with prior TIA or stroke should not be treated with prasugrel(6).

Notes for Editors

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.  To date prasugrel has been approved in more than 65 countries worldwide.

Prasugrel SPC  

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(8). In addition, ACS affects more than one million people in the United States annually(9). 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(10). 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 http://www.daiichisankyo.co.uk.

The company's world headquarters are in Tokyo. Its European base is located in Munich. DAIICHI SANKYO EUROPE has affiliates in 12 European countries in addition to a global manufacturing site located in Pfaffenhofen, Germany.

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 http://www.lilly.co.uk.    

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® is a registered trademark of Eli Lilly and Company.

UKEFF00778

References

(1) The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without ST-segment elevation of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. European Heart Journal. Published online 26 August 2011. Available at:
http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/Guidelines-NSTE-ACS-FT.pdf

(2) Small DS, Farid NA, Payne CD et al.  Effects of the Proton Pump Inhibitor Lansoprazole on the Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel.  Journal of Clinical Pharmacology 2008; 48 (4): 475-84

(3) Grech ED  et al. Acute coronary syndrome: unstable angina and non-ST segment elevation myocardial infarction.BMJ 2003; 326: 1259-1261

(4) Wijins W, Kolh P, Danchin N et al. Guidelines on myocardial revascularization The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). European Heart Journal. 2010; 31: 2501-2555

(5) Wiviott et al. Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2007;357:2001-15

(6) Efient (prasugrel) prescribing information EU. Daiichi Sankyo, Inc. and Eli Lilly and Company.  Prasugrel SPC.  Accessed August 2011

(7) 2011 ACCF/AHA Focused update of the guidelines for the management of patients with unstable angina/non-ST elevation myocardial infarction (Updated 2007 guideline): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines

(8)  British Heart Foundation Health Promotion Research Group. European Cardiovascular Disease Statistics 2008. http://www.ehnheart.org Accessed August 2011

(9) Roger VL, Go AS, Lloyd-Jones DM, et al. for the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics - 2011 update. Circulation. 2011;123:e1-e192.

(10)  WebMD Medical Reference in Collaboration with the Cleveland Clinic. Heart Disease: Coronary Artery Disease. http://www.webmd.com. Accessed August 2011

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