Specific data from this sub-analysis showed:
- In PLATO, higher overall rate of thrombotic CV events (adjusted hazard ratio [HR], 1.48 [95% CI, 1.32-1.66]) were associated in patients ≥75 years (n=2,878); Higher rates of Plato-defined Overall Major Bleeding were also associated with this patient population (adjusted HR, 1.11 [95% CI, 0.97-1.26]).
- The effects of BRILINTA compared to clopidogrel were consistent for thrombotic CV events, regardless of age. Thus, there was a similar reduction in the primary composite end point for patients aged ≥ 75 years of age (adjusted HR, 0.89 [95% CI, 0.74 -1.08]) and for patients < 75 years of age (adjusted HR, 0.84 [95% CI, 0.75 - 0.93]) (interaction p= 0.56).
- There was no significant interaction between age and the effects of treatment on Overall Major Bleeding and Non-CABG Major Bleeding. For PLATO-defined Overall Major Bleeding the adjusted HRs for BRILINTA vs. clopidogrel were 1.02 (95% CI, 0.82–1.27) and 1.04 (95% CI, 0.94–1.15) for patients aged ≥75 years and in younger patients, respectively (interaction P=0.89). For Non-CABG related Major Bleeding events, the adjusted HRs for BRILINTA vs. clopidogrel were 1.18 (95% CI, 0.87–1.59) in patients aged ≥75 years and 1.19 (95% CI, 0.99–1.43) in younger patients. (interaction P=0.96).
- Dyspnea and ventricular pauses were more common with BRILINTA than with clopidogrel treatment. With regards to dyspnea, rates were higher in elderly vs. younger patients in both treatment groups. In this analysis, dyspnea showed no evidence of an age by treatment interaction ( P=0.21). Similarly, ventricular pauses showed no evidence of an age-by treatment interaction.
- 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
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
- 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
BRILINTA is a registered trademark of the AstraZeneca group of companies.About PLATO PLATO (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 acute coronary syndrome (ACS) patients, 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 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 U.S. or our AZ&Me™ Prescription Savings programs, please visit: www.astrazeneca-us.com or call 1-800-AZandMe (292-6363). 2115102 9/12