AstraZeneca's Brilinta

The FDA approved Brilinta (ticagrelor) for reducing the rate of thrombotic cardiovascular events in patients with acute coronary syndrome when taken with aspirin.

The new antiplatelet drug Brilinta (ticagrelor) is marketed by AstraZeneca Pharmaceuticals LP and is FDA approved for reducing the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS) along with 75 to 100 mg of aspirin daily.¹

Ischemic heart disease is the leading cause of death worldwide, with ACS causing over 1.5 million deaths annually in the United States alone.²

According to current American Heart Association ACS guidelines, antiplatelet therapy is indicated in addition to standard care (anticoagulants, aspirin, and/or reperfusion, etc) for all patients who have had moderate to highrisk non-ST elevation myocardial infarction (NSTEMI) and for all who have had a ST-elevation MI (STEMI).³

The use of Brilinta is indicated in the current ACS guidelines as a second option for patients who cannot take clopidogrel.

Mechanism of Action

Brilinta is an orally active, reversible P2Y12 platelet inhibitor thought to bind to sites different from those of the other oral platelet inhibitors such as clopidogrel and prasurgrel. Whereas those 2 agents bind to the adenosine diphosphate (ADP) binding sites on platelets, Brilinta binds to an area different from the ADP binding site and is instead thought to affect ADP-dependent receptor activation.^1,4 Because it is not a prodrug like the other antiplatelet agents, Brilinta also has a more rapid onset of action.

Clinical Trials

The safety and efficacy of Brilinta was evaluated in the PLATelet inhibition and patient Outcomes (PLATO) study. This study was a randomized, double-blind, parallel study which compared Brilinta with clopidogrel, both in combination with aspirin and as standard therapy in patients who experienced ACS.⁵ Patients were treated for at least 6 months and up to 12 months. A total of 9333 patients were randomized to receive Brilinta, and 9291 patients were randomized to receive clopidogrel.

The primary efficacy end point was the composite of first occurrence of cardiovascular death, nonfatal MI, or nonfatal stroke. Each component of the primary efficacy end point was broken down into secondary end points.

Statistically significant results indicated Brilinta was superior over clopidogrel in all efficacy outcomes except for nonfatal stroke. Brilinta also showed superiority over clopidogrel in lowering stent thrombosis in patients who underwent primary percutaneous coronary intervention.⁴

Dosing¹

Brilinta should be initiated as a 180-mg (two 90-mg tablets) loading dose, followed by 90 mg twice daily. It can be administered with or without food.

Brilinta should be given with aspirin 75 to 100 mg daily for efficacy, but not more than the 100-mg dose according to manufacturer labeling, as the efficacy of Brilinta is decreased with these higher aspirin doses. Brilinta should not be administered with strong cytochrome P450 3A4 inhibitors or inducers, as these affect the metabolism of Brilinta. No dosing adjustments are needed based on age, gender, ethnicity, or hepatic or renal impairment. Smoking has been shown to decrease ticagrelor clearance by up to 22%, but dosage adjustments for smoking status are not necessary.

Safety and efficacy have not been studied in pediatric patients. Brilinta is classified as Pregnancy Category C and infant risk cannot be ruled out during breastfeeding.

Contraindications, Warnings, and Precautions¹

As with all drugs that inhibit platelet function, Brilinta does carry a boxed warning for increased bleeding. It is contraindicated in severe hepatic impairment and in patients with a history of intracranial hemorrhage. Brilinta must be stopped 5 days prior to surgery and before a coronary artery bypass graft.

Brilinta can increase serum creatinine and uric acid levels, but these should subside as therapy continues. Dyspnea and bradycarida are also potential adverse effects, but also should subside after therapy continues. Gynecomastia is a rare but possible side effect of Brilinta.

Common adverse effects are minor bleeding and headache. Health care professionals can access more information about Brilinta, including complete prescribing information, at www.brilintatouchpoints. com. PT

Dr. Winans is a pharmacy practice resident at the Harris County Hospital District in Houston, Texas. Dr. Challen is a clinical pharmacist specialist in primary care at Casa de Amigos Health Center in Houston, Texas.

References

1. Brilinta prescribing information. Wilmington, DE: AstraZeneca; July 2011.

2. Zafari AM. Myocardial infarction. Medscape Drug, Disease and Procedures Reference. http://emedicine.medscape.com/article/155919-overview#a0156. Accessed August 5, 2011.

3. O’Conner RE. Part 9: acute coronary syndromes: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2010;122:S422-S465.

4. van Giezen JJJ, Nilsson L, Berntsson P, et al. Ticagrelor binds to human P2Y₁₂ independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation. J Thromb Haemost. 2009;7(9):1556-1565.

5. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045-1057.