From a safety perspective, TRILOGY ACS showed that rates of TIMI major bleeding events (including life-threatening or fatal bleeds) did not differ significantly between the prasugrel plus aspirin and clopidogrel plus aspirin treatment groups in patients less than 75 years of age or in the overall study population.(1) In patients under age 75, non-CABG TIMI major bleeding occurred in 2.1 percent of prasugrel patients versus 1.5 percent of clopidogrel patients (HR=1.31, 95% CI: 0.81-2.11, P=0.27).(1) However, the rates of TIMI major or minor bleeding were higher in patients treated with prasugrel (3.3 percent of prasugrel patients versus 2.1 percent of clopidogrel patients; HR=1.54; 95% CI: 1.06-2.23; P=0.02).(1)
"TRILOGY ACS was designed to evaluate dual oral antiplatelet therapy in UA/NSTEMI patients who are managed medically without revascularization," said
An analysis performed to account for multiple recurrent ischemic events suggested a lower risk among participants < 75 years treated with prasugrel (HR=0.85; 95% CI: 0.72—1.00; P=0.044).(1)
A post-hoc exploratory analysis observed a trend for a lower risk in heart attack, stroke and death among patients treated with prasugrel beyond one year; HRs and 95% CIs for the time period of < 12 months versus the time period of > 12 months comparing prasugrel versus clopidogrel for the primary efficacy endpoint were 0.99 (0.84-1.16) versus 0.72 (0.54-0.97) (interaction P=0.07).(1)
"Large-scale clinical trials in understudied populations, such as TRILOGY ACS, are important regardless of the result because they generate a sizeable amount of information for the medical community," said
"While this is not the outcome we anticipated, we believe this study contributes to the knowledge base about ACS patients who are medically managed," said
The TRILOGY ACS study was conducted by
Approved by the
About TRILOGY ACS
TRILOGY ACS (TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes) began in
TRILOGY ACS was a multi-center, double-blind, randomized, controlled trial to evaluate the safety and efficacy of prasugrel plus aspirin compared to clopidogrel plus aspirin in UA/NSTEMI patients who were to be medically managed without revascularization. The primary endpoint was the time to occurrence of the first instance of the composite endpoint of CV death, heart attack or stroke. The sample size in the trial was selected to detect a 22 percent relative risk reduction in patients treated for up to 30 months with prasugrel compared with clopidogrel.(2)
Inclusion criteria for the study included at least one of the following high-risk features in UA/NSTEMI patients: age greater than 60 years, prior myocardial infarction, diabetes mellitus and/or prior revascularization (PCI or CABG).(2) Exclusion criteria included planned PCI or CABG, STEMI as the initial event, and medical management decision more than 72 hours after onset of event without clopidogrel treatment.(2)
Prasugrel loading and maintenance dosages in TRILOGY ACS were adjusted for the medically managed patient population enrolled and differ from the current indicated dosages for ACS-PCI patients.(2) Patients under the age of 75 and weighing more than 60 kg received a 10 mg MD of prasugrel. Prasugrel dosage adjustments (5 mg) were made for very elderly patients (75 years of age and older) and for those < 60 kg; patients with prior TIA/stroke were excluded.(2)
The current prasugrel indication in ACS patients intended for planned PCI, is a single 60 mg LD followed by a once-daily 10 mg MD.(3) A single 60 mg LD of prasugrel followed by a MD of prasugrel at a 5 mg once daily dose, co-administered with aspirin, can be considered for lower weight patients ( < 60 kg) with ACS-PCI.(3)
Safety endpoints evaluated included bleeding as measured by GUSTO and TIMI criteria; plus systematic collection of neoplasm data (all suspected events to be adjudicated by an Oncology Clinical End Point Committee).(2)
More than 90 percent of the patients in the study were treated with clopidogrel prior to randomization, per the guidelines for secondary prevention.(1) Although all patients in the study were committed to be treated medically without revascularization for the index event, a small percentage of patients less than 75 years of age underwent revascularization (7.9 percent) after randomization.(1)
More information on the TRILOGY ACS trial and its design is available at: http://clinicaltrials.gov/ct2/show/NCT00699998.
About Acute Coronary Syndrome
ACS, which includes heart attack and a type of chest pain called unstable angina (UA), affects more than one million people in
Each year, approximately 596,000 people undergo PCI, which typically includes the implantation of a stent that restores blood flow to blocked arteries in the heart. The number of UA or NSTEMI ACS patients worldwide who are managed without acute coronary interventions, such as PCI, has ranged from 32 percent to almost 60 percent over the last few years.(5,6) In many cases, these ACS patients may have complex coronary anatomy, comorbidities or other high-risk factors that prevent surgical intervention.
ACS results in significant illness and death, costing Americans more than
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), or are allergic to prasugrel or any of the ingredients in Effient.
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 Prescribing Information at http://pi.lilly.com/us/effient.pdf, including Boxed Warning regarding bleeding risk, and Medication Guide at http://pi.lilly.com/us/effient-ppi.pdf. You may also learn more about Effient at www.Effient.com.
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
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
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(1) Roe MT, Armstrong PW, Fox KAA, et al. Prasugrel versus Clopidogrel for Acute Coronary Syndromes without Revascularization. N Engl J Med. Published online
(2) Chin CT, Row MT, Fox KAA, et al. Study design and rationale of a comparison of prasugrel and clopidogrel in medically managed patients with unstable angina/non—ST —segment elevation myocardial infarction: The TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY ACS) trial.
(3) Effient (prasugrel) prescribing information.
(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 — 2012 update. Circulation. 2012;125:e2-e220.
(5) Fox KAA, Steg PG, Eagle KA, et al. Decline in rates of death and heart failure in acute coronary syndromes, 1999-2006.
(6) Chan MY, Mahaffey KW, Sun LJ, et al. Prevalence, predictors, and impact of conservative medical management for patients with non-ST-segment elevation acute coronary syndromes who have angiographically documented significant coronary disease. J Am Coll Cardiol. 2008;1:369-378.
(7) Kolansky DM. Acute coronary syndromes: Morbidity, mortality and pharmacoeconomic burden. Am J Manag Care. 2009;15:S36-S41.
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