FDA approves new oral antiplatelet agent ticagrelor

FDA has approved ticagrelor (Brilinta, AstraZeneca) tablets to reduce the rate of heart attack (myocardial infarction [MI]) and cardiovascular (CV) death in adult patients with acute coronary syndrome (ACS).

Ticagrelor, a new oral antiplatelet medicine, is indicated to reduce the rate of thrombotic cardiovascular events in patients with ACS (unstable angina [UA] non-ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial infarction [STEMI]).

Ticagrelor 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 shown by CV death and MI, with no difference in stroke. In patients treated with an artery-opening procedure known as percutaneous coronary intervention (PCI), ticagrelor reduces the rate of stent thrombosis. Ticagrelor has been studied in ACS in combination with aspirin. Maintenance doses of aspirin above 100 mg decreased the effectiveness of ticagrelor. Patients using ticagrelor should avoid maintenance doses of aspirin above 100 mg daily.

“We have learned from the controversies in stent research of recent years that coronary disease patients are not easy to manage on various prophylactic medication regimens or mechanical techniques,” Randy Vogenberg, PhD, told Formulary. Vogenberg is principal at the Institute for Integrated Healthcare in Sharon, Mass., and executive director of the Biologic Access & Finance program at The Jefferson School of Population Health in Philadelphia.

“Brilinta represents another tightrope to walk in using medication therapies to treat ACS. For managed care organizations and clinicians, this means enhanced vigilance in patient medication-therapy selection, as well as persistence, if desired clinical outcomes are ultimately to be achieved in real-world patient populations,” added Vogenberg, who is the author of Pharmacy Benefits: Management and Benefit Design, published by IFEBP.

FDA approval of ticagrelor is good news for patients, said David Brennan, CEO, AstraZeneca, in a company press release. “With over 1 million people affected by ACS in the U.S. each year, the fact that physicians have a new and more effective treatment option than clopidogrel to help reduce the rate of heart attack and cardiovascular death in these patients is an important advance.”

Now that ticagrelor is approved in the United States, AstraZeneca will begin the process of working with hospital formularies, protocol committees, government, and managed care reimbursement bodies to bring this medicine to patients. Navigating these steps, which are necessary before ticagrelor will be available to a substantial number of incident ACS patients, will be a key focus for the next 12 months.

The FDA approval is based upon data from the landmark PLATO (PLATelet Inhibition and Patient Outcomes) study, a superiority trial that compared treatment with ticagrelor to clopidogrel in 18,624 ACS patients worldwide.

As with other antiplatelet agents, ticagrelor can cause significant, sometimes fatal, bleeding. The PLATO study found no statistical difference between patients treated with ticagrelor and patients treated with clopidogrel in total major bleeding events (11.6% vs 11.2%), including fatal and fatal/life-threatening bleeding events. Non-CABG (coronary artery bypass graft) major + minor bleeding events (8.7% vs 7%) were more common with ticagrelor than with clopidogrel.

The most commonly observed adverse reactions associated with the use of ticagrelor versus clopidogrel were bleeding (11.6% vs 11.2%) and a feeling of breathlessness (dyspnea) (14% vs 8%).

As it does with all AstraZeneca products, the company will work to ensure that physicians and patients understand both the benefits and risks associated with ticagrelor. For ticagrelor, 1 of the ways AstraZeneca will help ensure that physicians and patients are appropriately informed about bleeding risk and the impact of aspirin dose on the effectiveness of ticagrelor is through a Risk Evaluation and Mitigation Strategy (REMS).

According to the American Heart Association, more than 1 million Americans are hospitalized with ACS every year.