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Guidelines based on study showing BRILINTA reduces risk of cardiovascular events over clopidogrel in patients with Acute Coronary Syndrome

Tue, 02/21/2012 - 5:45am
The Associated Press

WILMINGTON, Del.--(BUSINESS WIRE)--Feb 21, 2012-- AstraZeneca (NYSE: AZN) announced today that the American College of Chest Physicians (ACCP) has updated its guidelines on Antithrombotic Therapy and Prevention of Thrombosis to include a recommendation for giving the oral antiplatelet medicine, BRILINTA(R) (ticagrelor) tablets with low-dose aspirin to patients who suffer from Acute Coronary Syndrome (ACS).

Specifically, the guidelines state: For patients in the first year after an ACS who have not undergone percutaneous coronary intervention (PCI): -- We recommend dual antiplatelet therapy (ticagrelor 90 mg twice daily plus low-dose aspirin 75-100 mg daily or clopidogrel 75 mg daily plus low-dose aspirin 75-100 mg daily) over single antiplatelet therapy (Grade 1B).

-- We suggest ticagrelor plus low-dose aspirin over clopidogrel plus low-dose aspirin (Grade 2B).

For patients in the first year after an ACS who have undergone PCI with stent placement: -- We recommend dual antiplatelet therapy (ticagrelor 90 mg twice daily plus low-dose aspirin 75-100 mg daily, clopidogrel 75 mg daily plus low-dose aspirin, or prasugrel 10 mg daily plus low-dose aspirin over single antiplatelet therapy) (Grade 1B) -- We suggest ticagrelor 90 mg twice daily plus low-dose aspirin over clopidogrel 75 mg daily plus low-dose aspirin (Grade 2B) This is the first time that clinical treatment guidelines in the U.S.

have specifically suggested use of BRILINTA over clopidogrel.

"This new recommendation from ACCP is recognition of the clinical benefits of BRILINTA demonstrated in the PLATO trial," said Alex Gold, MD, Executive Director of Clinical Development, BRILINTA, AstraZeneca.

"In the months since FDA approval, BRILINTA has become an important treatment option for patients with ACS." The ACCP represents 18,400 members who provide patient care in the areas of pulmonary, critical care, and sleep medicine in the United States and more than 100 countries throughout the world. The ACCP was the first organization to develop evidence-based guidelines more than 25 years ago. The guidelines are referred to by a wide range of physicians, including hematologists, family physicians and internists.

The revised guidelines are available online at http://chestjournal.chestpubs.org and are published in the February 2012 issue of CHEST.

According to the American Heart Association (AHA), over 1 million Americans are hospitalized with ACS each year. It is also estimated that up to one in three patients could have a recurrent heart attack or die within one year of their first cardiovascular (CV) event.

BRILINTA tablets are the first and only oral antiplatelet treatment FDA-approved to significantly reduce CV death vs. clopidogrel in patients with ACS. The FDA approved label describes the efficacy and safety of BRILINTA, as compared to clopidogrel.

In patients with ACS, BRILINTA significantly reduced the rate of the primary composite end point of CV death, myocardial infarction (MI), or stroke vs. clopidogrel. The difference between treatments was driven by CV death and MI with no difference in stroke. The secondary end points included the individual components of CV death, MI, and stroke.

BRILINTA has been studied in ACS in combination with aspirin.

Maintenance doses of aspirin >100 mg decreased the effectiveness of BRILINTA. Avoid maintenance doses of aspirin >100 mg daily.

BRILINTA is an important advance for ACS patients and physicians, who now have a more effective treatment than clopidogrel, to reduce the rate of heart attack and CV death. BRILINTA is approved to be used with low-dose aspirin. After any initial dose, use with aspirin 75 mg - 100 mg per day.

BRILINTA MILESTONES Since receiving FDA approval, BRILINTA has achieved many significant milestones which have emphasized the value of BRILINTA as a treatment option for patients with ACS. In November 2011, a combined expert committee from ACCF, AHA and the Society for Cardiovascular Angiography and Interventions (SCAI) updated its guidelines for the management of patients undergoing PCI to provide a Class I recommendation for giving BRILINTA to patients undergoing PCI.

Additionally, AHA/ACCF also revised their Guidelines on Secondary Prevention and Risk Reduction Therapy to include BRILINTA, in combination with low-dose aspirin, as a Class 1 therapy to be taken twice daily for at least 12 months in patients receiving a bare-metal stent (BMS) or drug-eluting stent (DES) during PCI for ACS. A Class 1 recommendation is the highest recommendation provided by the guidelines committee and is defined as a "procedure/treatment that should be performed/administered" to patients, given it was found to be "useful/effective/beneficial." As expert leaders in the scientific community continue to embrace BRILINTA as a treatment option for ACS, there has also been a rapid acceptance of BRILINTA in top U.S. hospitals. As of January 30, 2012, BRILINTA was on formulary at 49% of the top 400 hospitals identified by AstraZeneca throughout the U.S.

BRILINTA INDICATIONS BRILINTA is indicated to reduce the rate of thrombotic cardiovascular events in patients with ACS (unstable angina UA, non--ST-elevation myocardial infarction NSTEMI, or ST-elevation myocardial infarction STEMI). BRILINTA has been shown to reduce the rate of a combined end point of CV death, MI, or stroke compared to clopidogrel. The difference between treatments was driven by CV death and MI with no difference in stroke. In patients treated with an artery-opening procedure known as percutaneous coronary intervention (PCI), BRILINTA reduces the rate of stent thrombosis.

BRILINTA has been studied in ACS in combination with aspirin.

Maintenance doses of aspirin above 100 mg decreased the effectiveness of BRILINTA. Avoid maintenance doses of aspirin above 100 mg daily.

IMPORTANT SAFETY INFORMATION ABOUT BRILINTA WARNING: BLEEDING RISK -- BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal, bleeding -- Do not use BRILINTA in patients with active pathological bleeding or a history of intracranial hemorrhage -- Do not start BRILINTA in patients planned to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue BRILINTA at least 5 days prior to any surgery -- Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of BRILINTA -- If possible, manage bleeding without discontinuing BRILINTA. Stopping BRILINTA increases the risk of subsequent cardiovascular events WARNING: ASPIRIN DOSE AND BRILINTA EFFECTIVENESS -- Maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA and should be avoided. After any initial dose, use with aspirin 75 mg - 100 mg per day CONTRAINDICATIONS -- BRILINTA is contraindicated in patients with a history of intracranial hemorrhage and active pathological bleeding such as peptic ulcer or intracranial hemorrhage. BRILINTA is also contraindicated in patients with severe hepatic impairment because of a probable increase in exposure; it has not been studied in these patients. Severe hepatic impairment increases the risk of bleeding because of reduced synthesis of coagulation proteins WARNINGS AND PRECAUTIONS -- Moderate Hepatic Impairment: Consider the risks and benefits of treatment, noting the probable increase in exposure to ticagrelor -- Premature discontinuation increases the risk of MI, stent thrombosis, and death -- Dyspnea was reported in 14% of patients treated with BRILINTA and in 8% of patients taking clopidogrel. Dyspnea resulting from BRILINTA is self-limiting. Rule out other causes -- BRILINTA is metabolized by CYP3A4/5. Avoid use with strong CYP3A inhibitors and potent CYP3A inducers. Avoid simvastatin and lovastatin doses >40 mg -- Monitor digoxin levels with initiation of, or any change in, BRILINTA therapy ADVERSE REACTIONS -- The most commonly observed adverse reactions associated with the use of BRILINTA vs clopidogrel were Total Major Bleeding (11.6% vs 11.2 and dyspnea (14% vs 8 -- In clinical studies, BRILINTA has been shown to increase the occurrence of Holter-detected bradyarrhythmias. PLATO excluded patients at increased risk of bradycardic events. Consider the risks and benefits of treatment Please read full Prescribing Information , including Boxed WARNINGS, and Medication Guide .

ABOUT PLATO The PLATO trial was a large (18,624 patients in 43 countries) head-to-head outcomes study of ticagrelor versus clopidogrel, both given in combination with aspirin and other standard therapy, designed to establish whether ticagrelor could achieve a clinically meaningful reduction in cardiovascular end points in ACS patients, above and beyond those afforded by clopidogrel.

The PLATO study demonstrated that treatment with BRILINTA led to a greater reduction in the primary end point - a composite of CV death, MI, or stroke - compared to patients who received clopidogrel (9.8% vs 11.7% at 12 months; 1.9% absolute risk reduction ARR; 16% relative risk reduction RRR; 95% CI, 0.77 to 0.92; P<0.001). The difference in treatments was driven by CV death and MI with no difference in stroke. In PLATO, the absolute difference in treatment benefit versus clopidogrel was seen at 30 days and the Kaplan-Meier survival curves continue to diverge throughout the 12-month treatment period.

It's important to know that BRILINTA does have a Boxed Warning for bleeding risks. BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal, bleeding. In addition, BRILINTA has a Boxed Warning concerning aspirin dose and BRILINTA effectiveness.

Maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA and should be avoided. After any initial dose, use with aspirin 75 mg - 100 mg per day.

The PLATO study also demonstrated that treatment with BRILINTA for 12 months was associated with a 21 percent RRR in CV death (4% vs 5.1%; 1.1% ARR; P0.001) and a 16 percent RRR in MI compared to clopidogrel at 12 months (5.8% vs 6.9%; 1.1% ARR; P<0.005).

The primary safety end point in the PLATO study was Total Major Bleeding (11.6% for BRILINTA and 11.2% for clopidogrel). In PLATO, non-CABG (coronary artery bypass graft) major + minor bleeding events (8.7% vs. 7 were more common with BRILINTA versus clopidogrel. The rate of non-CABG-related major bleeding was higher for BRILINTA (4.5 vs clopidogrel (3.8.

In a post hoc analysis of PLATO, it was determined that more than 80 percent of patients worldwide, with approximately 40 percent of patients in the US, received low maintenance doses of aspirin (100 mg or less). Results for US and non-US patients taking BRILINTA with these low maintenance doses of aspirin were similar. As with any unplanned subset analysis, the post hoc analysis should be treated with caution. Despite the need to treat such results cautiously, there appears to be good reason to restrict aspirin maintenance dosage accompanying ticagrelor to 100 mg. The PI states that maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA, and should be avoided. After any initial dose, BRILINTA should be used with maintenance aspirin doses of 75 mg - 100 mg per day.

About BRILINTA (ticagrelor) tablets BRILINTA is an oral antiplatelet treatment for acute coronary syndrome (ACS) in a new chemical class called cyclopentyltriazolopyrimidines (CPTPs). BRILINTA works by inhibiting platelet activation and has been shown to reduce the rate of thrombotic cardiovascular events, such as a heart attack or cardiovascular death, in patients with ACS. BRILINTA is a reversibly binding oral platelet P2Y12 adenosine diphosphate (ADP) receptor antagonist.

BRILINTA is available in 90-mg tablets to be administered with a single 180-mg oral loading dose (two 90-mg tablets) followed by a twice daily, 90-mg maintenance dose. Following an initial loading dose of aspirin, BRILINTA should be used with a maintenance dose of 75 mg - 100 mg aspirin once daily, 81-mg aspirin dose in the US.

BRILINTA is a trademark of the AstraZeneca group of companies.

About Acute Coronary Syndrome (ACS) ACS is an umbrella term for conditions that result from insufficient blood supply to the heart muscle. These conditions range from unstable angina (UA), non-ST-elevation myocardial infarction (NSTEMI), or ST-elevation myocardial infarction (STEMI).

Please see full US Full Prescribing Information including BOXED WARNINGS and Medication Guide at www1.astrazeneca-us.com/pi/brilinta.pdf.

NOTES TO EDITORS: About AstraZeneca AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

For more information about AstraZeneca in the US or our AZ&Me(TM) Prescription Savings programs, please visit: www.astrazeneca-us.com or call 1-800-AZandMe (292-6363).

1670003 2/2012 CONTACT: AstraZeneca Media Inquiries US Stephanie Jacobson, +1 302-885-5924 Mobile: +1 302-379-0443 or Julia Walker, +1 302-885-5172 Mobile: +1 610-350-8240 or Investor Inquiries US Ed Seage, +1 302-886-4065 Mobile: +1 302-373-1361 or Jorgen Winroth, +1 212-579-0506 Mobile: +1 917-612-4043 KEYWORD: UNITED STATES NORTH AMERICA DELAWARE INDUSTRY KEYWORD: HEALTH BIOTECHNOLOGY CARDIOLOGY PHARMACEUTICAL FDA GENERAL HEALTH SOURCE: AstraZeneca Copyright Business Wire 2012 PUB: 02/21/2012 10:00 AM/DISC: 02/21/2012 10:00 AM http://www.businesswire.com/news/home/20120221006395/

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