Brilinta (ticagrelor) - 3 indications

Scroll down for information on each indication:

• for the treatment of reduction of thrombotic events in patients with acute coronary syndrome; approved July 2011
• to reduce the risk of a first heart attack or stroke in high-risk patients with coronary artery disease; approved June 2020
• to reduce the risk of stroke in patients with acute ischemic stroke or high-risk transient ischemic attack; approved November 2020

General Information

Brilinta (ticagrelor) is a reversibly binding oral adenosine diphosphate (ADP) receptor antagonist. It selectively inhibits P2Y12, a key target receptor for ADP. ADP receptor blockade inhibits the action of platelets in the blood, reducing recurrent thrombotic events.

Brilinta is specifically indicated for the following:

• to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction, or ST elevation myocardial infarction)
• to reduce the risk of a first heart attack or stroke in high-risk patients with coronary artery disease
• to reduce the risk of stroke in patients with acute ischemic stroke (National Institutes of Health Stroke Scale score ≤5) or high-risk transient ischemic attack 

Brilinta is supplied as a tablet for oral administration. Scroll down for dosing/administration for each indication.

Mechanism of Action

Brilinta (ticagrelor) and its major metabolite reversibly interact with the platelet P2Y12 ADP-receptor to prevent signal transduction and platelet activation. Ticagrelor and its active metabolite are approximately equipotent.

Side Effects

Adverse events associated with the use of Brilinta may include, but are not limited to, the following:

• bleeding
• dyspnea

The Brilinta drug label comes with the following Black Box Warning: BLEEDING RISK: 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 undergoing urgent coronary artery bypass graft surgery (CABG). If possible, manage bleeding without discontinuing Brilinta. Stopping Brilinta increases the risk of subsequent cardiovascular events. ASPIRIN DOSE AND BRILINTA EFFECTIVENESS IN PATIENTS WITH ACS: Maintenance doses of aspirin above 100 mg daily reduce the effectiveness of Brilinta and should be avoided.

Indication 1 - for the treatment of reduction of thrombotic events in patients with acute coronary syndrome

approved July 2011

Dosing/Administration

180 mg (two 90 mg tablets) loading dose and continue treatment with 90 mg twice daily. After the initial loading dose of aspirin (usually 325 mg), use Brilinta with a daily maintenance dose of aspirin of 75-100 mg.

Clinical Trial Results

The FDA approval of Brilinta for ACS was based on a randomized double-blind study, PLATO. This study compared Brilinta (n=9333) to clopidogrel (n=9291), both given in combination with aspirin and other standard therapy, in subjects with acute coronary syndromes. The treatment duration was at least six months and for up to 12 months. Subjects who presented within 24 hours of onset of the most recent episode of chest pain or symptoms were randomized to receive Brilinta or clopidogrel. Brilinta was administered at a loading dose of 180 mg followed by a maintenance dose of 90 mg twice daily. Clopidogrel was administered at an initial loading dose of 300 mg, if previous clopidogrel therapy had not been given prior to randomization. Subjects undergoing PCI could receive an additional 300 mg of clopidogrel at investigator discretion. Concomitant aspirin was recommended at a loading dose of 160-500 mg. The study’s primary endpoint was the composite of first occurrence of cardiovascular death, non-fatal MI (excluding silent MI), or non-fatal stroke. Brilinta achieved greater efficacy over clopidogrel (9.8% vs. 11.7% at 12 months), without an increase in major bleeding (11.6% vs. 11.2%,). A statistically significant reduction in both CV death (4.0% vs. 5.1%) and heart attacks was also observed (5.8% vs. 6.9%) with no difference in stroke (1.5% vs. 1.3%). Brilinta also demonstrated significant results across multiple secondary efficacy endpoints including CV death (4.0% vs. 5.1%) all-cause mortality (4.5% vs. 5.9%); myocardial infarction (5.8% vs. 6.9%); the composite of myocardial infarction, stroke, and all-cause mortality (10.2% vs. 12.3%) and a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, recurrent cardiac ischemia, severe recurrent cardiac ischemia, and other arterial thrombotic events (14.6% vs. 16.7%). When PLATO minor bleeding was added to the major bleeding results, Brilinta showed an increase versus clopidogrel (16.1% vs. 14.6%). There was also an increase in non-procedural related bleeding with Brilinta.

Indication 2 - to reduce the risk of a first heart attack or stroke in high-risk patients with coronary artery disease

approved June 2020

Dosing/Administration

Coronary artery disease but no prior stroke or MI: administer 60 mg twice daily. Use Brilinta with a daily maintenance dose of aspirin of 75-100 mg.

Clinical Trial Results

The FDA approval of Brilinta to reduce the risk of a first heart attack or stroke in high-risk patients with coronary artery disease was based on positive results from the Phase III THEMIS trial. The trial showed a statistically significant reduction in the primary composite endpoint of major adverse cardiovascular (CV) events at 36 months with aspirin plus Brilinta 60mg versus aspirin alone in patients with CAD and type 2 diabetes (T2D) at high-risk of a first heart attack or stroke. The primary composite endpoint was driven by a reduction in heart attack and stroke.

Indication 3 - to reduce the risk of stroke in patients with acute ischemic stroke or high-risk transient ischemic attack

approved November 2020

Dosing/Administration

Initiate treatment with a 180-mg loading dose of Brilinta and then continue with 90 mg twice daily for up to 30 days. The treatment effect accrued early in the course of therapy. Use Brilinta with a loading dose of aspirin (300 to 325 mg)

Clinical Trial Results

The FDA approval of Brilinta for acute ischemic stroke or high-risk TIA was based on THALES, a randomized, placebo-controlled, double-blinded, international, multicenter, event-driven Phase III trial involving more than 11,000 patients from 28 countries. It tested the hypothesis whether aspirin plus Brilinta is superior to aspirin alone in preventing the composite of stroke and death in patients with non-cardioembolic acute ischemic stroke or high-risk TIA. Patients were randomized within 24 hours of onset of acute ischemic stroke or high-risk TIA symptoms and treated for 30 days. Study treatments were Brilinta 180mg loading dose on day 1, followed by 90mg twice daily on days 2-30, or matching placebo. All patients received open-label aspirin 300-325mg on day 1, followed by 75-100mg once daily on days 2-30. The primary efficacy outcome was the time to the composite endpoint of stroke and death at 30 days. Brilinta 90mg used twice daily and taken with daily aspirin for 30 days, reduced the rate of the primary composite endpoint of stroke and death by 17% compared to aspirin alone in patients with an acute ischemic stroke or TIA. This was a statistically significant and clinically meaningful reduction. The primary composite endpoint was driven by a reduction in stroke. The risk for severe bleeding events was 0.5% in patients receiving aspirin plus Brilinta and 0.1% for aspirin alone.