CardioSource WorldNews December 2014 - Page 5

CardioSource WorldNews …the App! BRILINTA® (ticagrelor) Tablets Table 2 CABG bleeds (KM%) Patients with CABG BRILINTA Clopidogrel N=770 N=814 Total Major 85.8 86.9 Fatal/Life-threatening 48.1 47.9 Fatal 0.9 1.1 Although the platelet inhibition effect of BRILINTA has a faster offset than clopidogrel in in vitro tests and BRILINTA is a reversibly binding P2Y12 inhibitor, PLATO did not show an advantage of BRILINTA compared to clopidogrel for CABG-related bleeding. When antiplatelet therapy was stopped 5 days before CABG, major bleeding occurred in 75% of BRILINTA treated patients and 79% on clopidogrel. No data exist with BRILINTA regarding a hemostatic benefit of platelet transfusions. Drug Discontinuation In PLATO, the rate of study drug discontinuation attributed to adverse reactions was 7.4% for BRILINTA and 5.4% for clopidogrel. Bleeding caused permanent discontinuation of study drug in 2.3% of BRILINTA patients and 1.0% of clopidogrel patients. Dyspnea led to study drug discontinuation in 0.9% of BRILINTA and 0.1% of clopidogrel patients. Common Adverse Events A variety of non-hemorrhagic adverse events occurred in PLATO at rates of 3% or more. These are shown in Table 3. In the absence of a placebo control, whether these are drug related cannot be determined in most cases, except where they are more common on BRILINTA or clearly related to the drug’s pharmacologic effect (dyspnea). Table 3 Percentage of patients reporting non-hemorrhagic adverse events at least 3% or more in either group BRILINTA Clopidogrel N=9235 N=9186 Dyspnea1 13.8 7.8 Headache 6.5 5.8 Cough 4.9 4.6 Dizziness 4.5 3.9 Nausea 4.3 3.8 Atrial fibrillation 4.2 4.6 Hypertension 3.8 4.0 Non-cardiac chest pain 3.7 3.3 Diarrhea 3.7 3.3 Back pain 3.6 3.3 Hypotension 3.2 3.3 Fatigue 3.2 3.2 Chest pain 3.1 3.5 1 Includes: dyspnea, dyspnea exertional, dyspnea at rest, nocturnal dyspnea, dyspnea paroxysmal nocturnal Bradycardia In clinical studies BRILINTA has been shown to increase the occurrence of Holterdetected bradyarrhythmias (including ventricular pauses). PLATO excluded patients at increased risk of bradycardic events (e.g., patients who have sick sinus syndrome, 2nd or 3rd degree AV block, or bradycardic-related syncope and not protected with a pacemaker). In PLATO, syncope, pre-syncope and loss of consciousness were reported by 1.7% and 1.5% of BRILINTA and clopidogrel patients, respectively. In a Holter substudy of about 3000 patients in PLATO, more patients had ventricular pauses with BRILINTA (6.0%) than with clopidogrel (3.5%) in the acute phase; rates were 2.2% and 1.6% respectively after 1 month. Gynecomastia In PLATO, gynecomastia was reported by 0.23% of men on BRILINTA and 0.05% on clopidogrel. Other sex-hormonal adverse reactions, including sex organ malignancies, did not differ between the two treatment groups in PLATO. Lab abnormalities Serum Uric Acid: Serum uric acid levels increased approximately 0.6 mg/dL from baseline on BRILINTA and approximately 0.2 mg/dL on clopidogrel in PLATO. The difference disappeared within 30 days of discontinuing treatment. Reports of gout did not differ between treatment groups in PLATO (0.6% in each group). Serum Creatinine: In PLATO, a >50% increase in serum creatinine levels was observed in 7.4% of patients receiving BRILINTA compared to 5.9% of patients receiving clopidogrel. The increases typically did not progress with ongoing treatment and often decreased with continued therapy. Evidence of reversibility upon discontinuation was observed even in those with the greatest on treatment increases. Treatment groups in PLATO did not differ for renal-related serious adverse events such as acute renal failure, chronic renal failure, toxic nephropathy, or oliguria. Postmarketing Experience The following adverse reactions have been identified during post-approval use of BRILINTA. Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders – Hypersensitivity reactions including angioedema [see Contraindications (4.4) in full Prescribing Information]. D