AstraZeneca (NYSE: AZN) today announced that BRILINTA ® (ticagrelor) tablets received Plan Preferred Tier 2 formulary access on Medco Health Solutions’ National commercial formulary and Preferred Brand formulary status on its Medicare Part D drug list. “This is an important milestone recognizing the clinical value of BRILINTA,” said Alex Gold, MD, Executive Director of Clinical Development, BRILINTA, AstraZeneca. The addition of BRILINTA to the Medco Health Solutions formulary will provide physicians and ACS patients with an important treatment option to reduce the rate of thrombotic CV events. Medco Health Solutions, Inc. is a leading Pharmacy Benefit Manager (PBM) with the nation's largest mail order pharmacy operations and more than 60 million members. In addition to Medco, BRILINTA is now on formulary at 49 percent of the top 400 hospitals throughout the U.S. A full list of available formularies for BRILINTA can be found on Fingertip Formulary, a website that offers formulary drug status on the most commonly prescribed drugs across a comprehensive list of health plans. 1 Recently in February 2012, the American College of Chest Physicians (ACCP) updated its guidelines on Antithrombotic Therapy and Prevention of Thrombosis to include a recommendation for giving BRILINTA with low-dose aspirin to patients in the first year after an ACS. This is the first time that clinical treatment guidelines in the U.S. have specifically suggested use of BRILINTA over clopidogrel. 2 In November 2011, a combined expert committee from American College of Cardiology Foundation (ACCF), the American Heart Association (AHA) and the Society for Cardiovascular Angiography and Interventions (SCAI) updated its guidelines for the management of patients undergoing percutaneous coronary intervention (PCI), an artery-opening procedure, to provide a Class I recommendation for giving BRILINTA to patients undergoing PCI with stenting. 3 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." Additionally, AHA/ACCF also revised their Guidelines on Secondary Prevention and Risk Reduction Therapy to include BRILINTA, in combination with low-dose aspirin 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. 4 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 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.For patients that require BRILINTA beyond their hospital stay, a savings card program is available based on eligibility. Commercially insured and cash-paying patients may be eligible for one free prescription and will get up to $75 off (after the first $25) on each of their next 11 refills. Patients covered through Medicare, Medicaid or a resident of Massachusetts may be eligible for one month of free prescription. Patients can find out more at www.BRILINTAtouchpoints.com or by calling 1-888-412-7454. AstraZeneca also offers a U.S. patient assistance program for BRILINTA through its AZ&ME TM Prescription Savings Program. To determine eligibility, patients can visit www.AZandMe.com or call 1-800-AZandMe (292-6363). 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
- 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
- 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
- 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
- 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
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; P=0.001) 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 were more common with BRILINTA versus clopidogrel (8.7% vs 7% respectively). 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) tabletsBRILINTA is an oral antiplatelet treatment for 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 CV death, in patients with ACS. BRILINTA is a reversibly binding oral platelet P2Y 12 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 registered 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). 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™ Prescription Savings programs, please visit: www.astrazeneca-us.com or call 1-800-AZandMe (292-6363). References
- Fingertip Formulary. February 7, 2012.
- Guyatt GH, Akl EA, Crowther M, et al. Executive Summary : Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141;7S-47S.
- Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol 2011;58:e44-e122.
- Smith SC Jr, Benjamin EJ, Bonow RO et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124:2458-2473.
- Prescribing Information for BRILINTA. AstraZeneca Pharmaceuticals LP, Wilmington, DE.