Blood Thinner Brilinta Treats Acute Coronary Syndrome

Approved by the FDA in July 2011, AstraZeneca’s Brilinta (ticagrelor tablets) is a twice-daily treatment to reduce the rate of myocardial infarction and cardiovascular death in adult patients with acute coronary syndrome, a condition affecting more than 1 million Americans every year, according to the American Heart Association.

Combined with daily maintenance doses of aspirin of less than 100 milligrams, Brilinta is indicated to reduce the rate of thrombotic cardiovascular events in patients with unstable angina, non—ST-elevation myocardial infarction or ST-elevation myocardial infarction. Symptoms associated with those conditions include chest pain and high blood pressure.

The platelet inhibitor also reduces the rate of stent thrombosis in patients who have recently undergone percutaneous coronary intervention. Compared to rival clot buster Plavix (clopidogrel) in various clinical studies, Brilinta has been shown to reduce the rate of cardiovascular death, myocardial infarction or ischemic stroke in acute coronary syndrome patients.

Pharmacology and Pharmacokinetics

A 6-week study examined both acute and chronic platelet inhibition effects by ticagrelor and clopidogrel in response to platelet aggregation following the activation of adenosine diphosphate receptor P2Y₁₂ in patients. Mean maximum inhibition of platelet aggregation following the most recent dose was 88 percent for ticagrelor and 62 percent for clopidogrel. After 24 hours, IPA in the ticagrelor group was similar to IPA in the clopidogrel group — indicating that patients who miss a ticagrelor dose would still maintain IPA similar to patients treated with clopidogrel — and after 5 days, IPA in the ticagrelor group was similar to IPA in the placebo group.

At the conclusion of the study, researchers found transitioning from Plavix to Brilinta resulted in an absolute IPA increase of 26.4 percent, while transitioning from Brilinta to Plavix resulted in an absolute IPA decrease of 24.5 percent.

Following oral administration, Cytochrome P450 3A4 enzymes metabolize ticagrelor and form its major active metabolite, and then both extensively bind to human plasma proteins. The mean half-life is approximately 7 hours for ticagrelor and 9 hours for the active metabolite, and the primary elimination route for the major metabolite of ticagrelor is most likely to be biliary secretion.

Dosage and Administration

A 90-milligram Brilinta tablet is taken orally twice daily with or without food. After a typical 325-milligram loading dose of aspirin, patients are recommended to use Brilinta with a daily maintenance dose of aspirin under 100 milligrams, as the drug’s effectiveness decreases when combined with doses of aspirin above that benchmark, according to AstraZeneca.

Each film-coated dose of Brilinta is supplied as a round, biconvex, yellow tablet marked with a “90” above “T” on one side.

Clinical Trials

In a randomized, double-blind study comparing the effectiveness of ticagrelor to clopidogrel in 18,624 patients worldwide who presented within 24 hours of onset of the most recent episode of chest pain or other acute coronary symptoms, Brilinta was shown to “reduce the rate of a combined endpoint of cardiovascular death, myocardial infarction or stroke compared to clopidogrel, (though) the difference between treatments was driven by CV death and MI, with no difference in stroke.”

Additionally, among 11,289 patients with percutaneous coronary intervention receiving any stent during the study, there was a lower risk of stent thrombosis with ticagrelor use than with clopidogrel use.

Contraindications, Warnings and Precautions

As ticagrelor increases the overall risk of bleeding, Brilinta is contraindicated in patients with a history of intracranial hemorrhage, active pathological bleeding such as peptic ulcer or severe heptic impairment, which increases that risk as it reduces synthesis of coagulation proteins. Brilinta is also contraindicated in patients with hypersensitivity to ticagrelor.

While no differences in the safety and effectiveness of Brilinta were observed among adult and elderly age groups in clinical trials, those factors have not been established in the pediatric population.

Adverse reactions to Brilinta during the clinical study included major bleeding events and shortness of breath, which was reported in 14 percent of patients taking ticagrelor and in 8 percent of patients taking clopidogrel.