New Analysis of Data Presented at AHA Regarding Effect of Effient® (Prasugrel) on Cardiovascular Events in STEMI Patients According to Timing of PCI

Data provide further insight into how the timing of PCI may affect outcomes in STEMI patients at risk for future cardiovascular events

News provided by

Eli Lilly and Company

Nov 16, 2011, 03:00 ET

ORLANDO, Fla., Nov. 16, 2011 /PRNewswire/ -- An analysis of the TRITON-TIMI 38 trial presented today in an oral session at the American Heart Association (AHA) Scientific Sessions meeting examined the effect of Effient® (prasugrel) on cardiovascular (CV) events (CV death, myocardial infarction [MI] and stroke) compared to clopidogrel relative to the timing of percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) patients with ST-segment elevation myocardial infarction (STEMI).(1)

At 15 months, primary PCI patients with STEMI had an 11 percent relative risk reduction in CV events, and secondary PCI patients had a 35 percent relative risk reduction with Effient compared to clopidogrel (HR 0.89, 95% CI 0.69-1.13; and HR 0.65, 95% CI 0.46-0.93, respectively). Absolute risk reduction for Effient compared to clopidogrel was 1.3 percent for the primary PCI group and 4.6 percent for the secondary PCI group.(1)

"Not all ST-elevation MI patients are treated with primary PCI; therefore, understanding the effects of more potent inhibition of platelets in ACS patients who are treated with primary PCI or those treated with delayed PCI is important for choosing antiplatelet therapies," said lead author Jacob A. Udell, MD, MPH, Clinical Fellow, Cardiovascular Medicine, Brigham & Women's Hospital. "These data demonstrate that efficacy and bleeding rates for Effient are consistent with the overall TRITON-TIMI 38 trial results irrespective of when STEMI patients undergo intended PCI."

In the study, primary PCI was defined as PCI within 12 hours from onset of acute coronary syndrome (ACS) symptoms and secondary PCI was defined as PCI more than 12 hours after initial onset or initial medical therapy. Of the 3,534 STEMI patients from the TRITON-TIMI 38 trial who were included in this analysis, 2,340 (68 percent) underwent primary PCI and 1,085 underwent secondary PCI. Randomization to Effient or clopidogrel occurred at presentation if primary PCI was intended or at the time of secondary PCI. The primary endpoint of the analysis was a reduction in the composite of CV death, MI and stroke.

In this analysis, TIMI major non-CABG bleeding events at 15 months occurred in 3 percent of prasugrel-treated primary PCI patients and 1.9 percent of clopidogrel-treated patients (HR=1.52, p=0.13); TIMI non-CABG major or minor bleeding occurred in this patient group in 5 percent of clopidogrel-treated patients and 6 percent of prasugrel-treated patients (HR=1.33, p=0.12). In secondary PCI patients, TIMI major non-CABG bleeding events occurred in 2.5 percent of clopidogrel-treated patients and 0.9 percent of prasugrel-treated patients (HR=0.39, p=0.07); TIMI non-CABG major or minor bleeding events occurred in 5 percent of clopidogrel-treated patients compared to 3 percent of prasugrel-treated patients (HR=0.57, p=0.09).(1) TIMI major non-CABG bleeding events associated with prasugrel as compared to clopidogrel were consistent in the STEMI cohort compared to the overall trial. Within the PCI subgroup, the hazard of bleeding with primary PCI at 15 months was HR 1.52 [CI 0.87-2.65] and for secondary PCI at 15 months was HR 0.39 [CI 0.14-1.11].(1)

Overall TRITON-TIMI 38 Study Methodology

TRITON-TIMI 38 was a head-to-head study comparing Effient (60-mg loading dose [LD], followed by a 10-mg once-daily maintenance dose) plus aspirin (ASA) with Plavix (clopidogrel) (300-mg LD, followed by a 75-mg once-daily maintenance dose) plus ASA in 13,608 patients with ACS managed with percutaneous coronary intervention (PCI), a procedure to open blockages in heart arteries, including the use of coronary stenting. The median duration of study treatment was 14.5 months.(2)

The primary endpoint of the study was the combined incidence of cardiovascular death, non-fatal heart attack or non-fatal stroke in patients followed for 6-15 months following PCI. The study showed that treatment with Effient 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 Plavix in people with chest pain at rest or milder heart attacks (unstable angina/ non-ST segment myocardial infarction) (9.3 vs. 11.2 percent respectively, p=0.002) and a 21 percent significant reduction in the combined endpoint in people with more severe heart attacks (ST elevation myocardial infarction) (9.8 vs. 12.2 percent respectively, p=0.019).(3) This corresponds to a 1.9 percent absolute risk reduction for UA/NSTEMI patients treated with Effient and a 2.4 percent absolute risk reduction for STEMI patients treated with Effient.(2) TRITON-TIMI 38 patients treated with Effient also experienced a 50 percent relative risk reduction (corresponding to 1.3 percent absolute risk reduction) in stent-related clots when compared with Plavix, regardless of stent type (1.1 percent vs. 2.4 percent respectively, p<0.001).(2) In TRITON, the risk of non-coronary artery bypass graft (non-CABG) major bleeding, including fatal bleeding, was higher with Effient (2.2 percent incidence) compared with Plavix (1.7 percent incidence) (p=0.029).(2) The rate of TIMI major or minor bleeding was significantly greater with Effient than Plavix (5.0 percent vs. 3.8 percent respectively, p=0.002). The risk of coronary artery bypass graft (CABG) major bleeding, including fatal bleeding, was higher with Effient (13.4 percent incidence) than Plavix (3.2 percent incidence) (p<0.001).(2) In TRITON-TIMI 38, the LD of Plavix was delayed relative to the placebo-controlled trials that supported its approval for ACS.

Compared with the overall study population, a higher risk of serious bleeding among Effient patients was most evident in three distinct patient populations that are readily identifiable: patients who weighed less than 132 lbs (60 kg), patients who were 75 years of age or older and patients who have had a prior transient ischemic attack (TIA) or stroke.(3) A 5 mg maintenance dose may be considered for patients who weigh less than 132 lbs.(3) Effient is generally not recommended for use in patients 75 years or older,(3) except in high risk patients (diabetes or prior MI), where its effects appears to be greater and its use may be considered.(3) Patients with prior TIA or stroke should not be treated with Effient.(3)

About Effient

Daiichi Sankyo Company, Limited (TSE: 4568), and Eli Lilly and Company (NYSE: LLY) co-developed Effient, an oral antiplatelet agent discovered by Daiichi Sankyo and its Japanese research partner, Ube Industries, Ltd. Effient helps keep blood platelets from clumping together and developing a blockage in an artery. Effient is approved by the U.S. Food and Drug Administration for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with ACS who are managed with an artery-opening procedure known as PCI. PCI usually includes the placement of a stent to help keep the artery open.

About Acute Coronary Syndrome

ACS, which includes heart attack and a type of chest pain called unstable angina, affects more than one million people in the United States annually.(4) The annual incidence of new heart attacks is estimated to be approximately 610,000 and about 325,000 people will have a recurrent attack.(4) Each year, approximately 645,000 people with ACS are managed with PCI, which typically includes the implantation of a stent that restores blood flow to blocked arteries in the heart.(5) ACS results in significant illness and death, costing Americans more than $150 billion each year.(5) Nearly 60 percent of the U.S. healthcare costs of ACS are due to re-hospitalization.(5) Strategies to prevent recurrent heart attacks and re-hospitalization are important to improve patient outcomes and reduce the cost burden of ACS.(5)

Important Safety Information

What is the most important information patients should know about Effient?

Effient® (prasugrel) can cause bleeding. If patients have unexplained or excessive bleeding while on Effient, they should contact their doctor right away as some bleeding can be serious, and sometimes fatal. Patients should not take Effient if they currently have abnormal bleeding, such as stomach or intestinal bleeding, bleeding in their head, or have a history of stroke, or “mini-stroke” (also known as transient ischemic attack or TIA).

Patients should get medical help right away if they suddenly have slurring of speech, weakness or numbness in one part of their body, blurry vision, and/or severe headache. These may be symptoms of a stroke or TIA. If patients have a stroke or TIA while taking Effient, their doctor will probably stop Effient.

Before having any surgery, patients should talk to their doctor about stopping Effient. If possible, patients should stop taking Effient at least 1 week (7 days) before any surgery, as instructed by their doctor who prescribed Effient.

Patients may also have a higher risk of bleeding if they take Effient and they: a) are age 75 or older, b) weigh less than 132 pounds, c) are taking anticoagulants (eg, warfarin) or regular daily use of NSAIDs, d) have had recent trauma, such as an accident or surgery, e) have severe liver problems, or f) have a stomach ulcer.

Patients should not stop taking Effient without talking to the doctor who prescribes it for them. People who are treated with angioplasty and have a stent, and stop taking Effient too soon, have a higher risk of a blood clot in the stent, having a heart attack, or dying.

What should patients tell their doctor before taking Effient?

Patients should tell their doctor about all of their medical conditions, allergies, and medicines they are taking.

What are the possible side effects of Effient?

Bleeding is the most common side effect of Effient.

TTP, a rare but life-threatening condition, has been reported with Effient, sometimes after a short time (less than 2 weeks). Patients should get medical attention right away if they develop the following unexpected symptoms of TTP: fever, weakness, yellowing of the skin or eyes, or if skin becomes very pale or dotted with purple spots.

Serious allergic reactions can happen with Effient, or if the patient has had a serious allergic reaction to the medicines Plavix® (clopidogrel) or ticlopidine. Patients should get medical help right away if they get any of these symptoms of a severe allergic reaction: swelling or hives of their face, lips, in or around their mouth, or throat, trouble breathing or swallowing, chest pain or pressure, dizziness or fainting.

Other side effects may occur.

For more information about Effient, please see the Full Prescribing Information at http://pi.lilly.com/us/effient.pdf, including Boxed Warning regarding bleeding risk and Medication Guide http://pi.lilly.com/us/effient-ppi.pdf. You may also learn more about Effient at www.Effient.com.

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.

Daiichi Sankyo, Inc., headquartered in Parsippany, New Jersey, is a member of the Daiichi Sankyo Group. For more information on Daiichi Sankyo, Inc., please visit www.dsi.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 Effient 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.

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

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

P-LLY

(1) Udell JA et al. Benefit of Prasugrel in ST-elevation Myocardial Infarction According to Timing of Percutaneous Coronary Intervention: Insights from the TRITON-TIMI 38 Study. To be presented at the American Heart Association Scientific Sessions; November 2011; Orlando FL.

(2) Wiviott, S.D. et al. Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes. New England Journal of Medicine 2007 Vol 357 (20); 2001-2015.

(3) Effient (prasugrel) prescribing information. Daiichi Sankyo, Inc. and Eli Lilly and Company.

(4) 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.

(5) Kolansky DM. Acute coronary syndromes: Morbidity, mortality, and pharmacoeconomic burden. Amer. J. of Managed Care. 2009;15:S36-S41.

(Logo: http://photos.prnewswire.com/prnh/20110329/DE73362LOGO )

SOURCE Eli Lilly and Company