BRILINTA is the first and only oral antiplatelet FDA-approved to significantly reduce cardiovascular (CV) death vs clopidogrel in patients with ACS. The FDA-approved label describes the efficacy and safety of BRILINTA, as compared to clopidogrel.BRILINTA is indicated to reduce the rate of thrombotic CV 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. BRILINTA is an important advance for patients with ACS and physicians, as it is 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. 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 US have specifically suggested use of BRILINTA over clopidogrel. 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), to provide a Class I recommendation for giving BRILINTA to patients undergoing PCI with stenting. A Class I 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.
IMPORTANT SAFETY INFORMATION ABOUT BRILINTAWARNING: 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
About PLATOPLATO (PLATelet Inhibition and Patient Outcomes) was a large (18,624 patients in 43 countries), head-to-head patient outcomes study of BRILINTA versus clopidogrel, both given in combination with aspirin and other standard therapy. The study was designed to establish whether BRILINTA could achieve a clinically meaningful reduction in cardiovascular (CV) events in patients with ACS, above and beyond that afforded by clopidogrel. Patients were treated for at least 6 months and up to 12 months. PLATO demonstrated that treatment with BRILINTA led to a significantly 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 continued to diverge throughout the 12-month treatment period. The PLATO study also demonstrated that treatment with BRILINTA for 12 months was associated with a 21% RRR in CV death (4% vs 5.1%; 1.1% ARR; P=0.001) and a 16% 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 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%). Dyspnea was reported in 14% of patients treated with BRILINTA and in 8% of patients treated with clopidogrel. Dyspnea was usually mild to moderate in intensity and often resolved during continued treatment.
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). About Angiomax (bivalirudin) for injection Angiomax (bivalirudin) is a direct thrombin inhibitor with a naturally reversible mechanism of action and a 25 minute half-life. In the United States, Angiomax with provisional use of glycoprotein IIb/IIIa inhibitor (GPI) is indicated for use in patients undergoing angioplasty, also called percutaneous coronary intervention (PCI), and in patients with, or at risk of, heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis syndrome (HIT/HITTS) undergoing PCI. In addition, Angiomax is indicated for use as an anticoagulant in patients with unstable angina (UA) undergoing percutaneous transluminal coronary angioplasty (PTCA). Angiomax is intended for use with aspirin. Angiomax is not approved for use in ACS patients not undergoing PCI or PTCA. Important Safety Information for Angiomax (bivalirudin) for injection Angiomax (bivalirudin) is contraindicated in patients with active major bleeding or hypersensitivity (e.g., anaphylaxis) to Angiomax or its components. Hemorrhage can occur at any site. An unexplained fall in blood pressure or hematocrit, or any unexplained symptom, should lead to serious consideration of a hemorrhagic event and cessation of Angiomax administration. Angiomax should be used with caution in patients with disease states associated with an increased risk of bleeding. In gamma brachytherapy, an increased risk of thrombus formation, including fatal outcomes, has been associated with the use of Angiomax. The most common adverse reaction for Angiomax was bleeding (28%). Other adverse reactions (>0.5%) for Angiomax were headache, thrombocytopenia, and fever. The most common adverse events for Angiomax in clinical trials comparing Angiomax and heparin were back pain, pain, nausea, headache and hypotension. The incidence of these adverse events was comparable in both the Angiomax and heparin groups in these trials. An unexplained fall in blood pressure or hematocrit, or any unexplained symptom, should lead to serious consideration of a hemorrhagic event and cessation of Angiomax administration. Angiomax is contraindicated in patients with active major bleeding or hypersensitivity to Angiomax or its components. Please see full prescribing information available at http://www.angiomax.com. About Cangrelor Cangrelor is an investigational intravenous small molecule antiplatelet agent not approved for commercial use in any market. Cangrelor was exclusively licensed in December 2003 by The Medicines Company from AstraZeneca.
About AstraZenecaAstraZeneca 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 U.S. or our AZ&Me™ Prescription Savings programs, please visit: www.astrazeneca-us.com or call 1-800-AZandMe (292-6363). About The Medicines Company The Medicines Company provides medical solutions to improve health outcomes for patients in acute and intensive care hospitals worldwide. These solutions comprise medicines and knowledge that directly impact the survival and well-being of critically ill patients. Statements contained in this press release about The Medicines Company that are not purely historical, and all other statements that are not purely historical, may be deemed to be forward-looking statements for purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words "believes," "anticipates," "plans" and "expects" and similar expressions are intended to identify forward-looking statements. These forward-looking statements involve known and unknown risks and uncertainties that may cause the Company's actual results, levels of activity, performance or achievements to be materially different from those expressed or implied by these forward-looking statements. Important factors that may cause or contribute to such differences include whether the Company's products will advance into clinical trials or through the clinical trials process on a timely basis or at all, whether results of preclinical studies and clinical trials such as the results described above will be indicative of results in later clinical trials, whether clinical trial results will warrant submission of applications for regulatory approval, whether the Company will be able to obtain regulatory approvals, whether physicians, patients and other key decision-makers will accept clinical trial results, and such other factors as are set forth in the risk factors detailed from time to time in the Company's periodic reports and registration statements filed with the Securities and Exchange Commission including, without limitation, the risk factors detailed in the Company's Annual Report on Form 10-K filed on February 29, 2012, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.