The therapy was previously approved to reduce the risk of cardiovascular death, MI, and stroke in patients with ACS or previous MI.
The US Food and Drug Administration (FDA) has approved ticagrelor (Brilinta; AstraZeneca) to reduce the risk of stroke in patients with acute ischemic stroke (AIS) or high-risk transient ischemic attack (TIA).
The new indication expands use of ticagrelor beyond cardiovascular disease, to patients with mild to moderate stroke.
The FDA had originally accepted ticagrelor’s supplemental new drug application (sNDA) and granted it priority review designation in July. The sNDA approval was based on findings from the phase 3 THALES trial (NCT03354429), which demonstrated that aspirin plus 90-mg ticagrelor significantly reduced the rate of the composite of stroke and death compared with aspirin alone in patients with AIS or TIA who were not undergoing intravenous or endovascular thrombosis.
"One in 4 patients who have had a stroke will experience a second one, with the risk particularly high within the first 30 days,” Clay Johnston, MD, PhD, lead investigator for THALES, and dean, Dell Medical School, University of Texas in Austin, said in a statement. “The approval of Brilinta in combination with aspirin is an important advancement to reduce the risk of recurrent stroke and much-awaited good news for physicians and patients.”
The primary composite end point of stroke and death was reduced by 17% (absolute risk reduction, 1.1%; hazard ratio [HR], 0.83; 95% CI, 0.71–0.96; P = .015) for patients with AIS or TIA who received the ticagrelor twice daily with daily aspirin for 30 days compared with aspirin alone.
Severe bleeding, the primary safety end point of the study, occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and 7 patients (0.1%) in the aspirin group (HR, 3.99; 95% CI, 1.74–9.14; P = .001). A composite outcome event of intracranial hemorrhage or fatal bleeding occurred in 22 (0.4%) and 6 (0.1%) patients in the ticagrelor-aspirin and aspirin groups, respectively.
Ticagrelor has been previously approved to reduce the risk of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of MI. The treatment also has shown to reduce the risk of stent thrombosis in patients who have been stented for treatment of ACS.
In June 2020, the drug was approved to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) who are at high risk for such events. That was the first regulatory approval for aspirin plus ticagrelor dual antiplatelet therapy in those who are high-risk but have no history of heart attack or stroke.
AstraZeneca noted that patients with AIS or high-risk TIA should initiate treatment with a 180-mg loading dose of ticagrelor and then continue with 90-mg ticagrelor twice daily for up to 30 days. During initiation, patients should also receive a loading dose of aspirin (300 to 325 mg).
Ticagrelor 60- and 90-mg tablets can cause significant and sometimes fatal bleeding. The treatment should not be used in patients with active pathological bleeding or a history of intracranial hemorrhage, or in patients undergoing urgent coronary artery bypass graft surgery. Other contraindications include patients with hypersensitivity to ticagrelor or any component of the product.
Maintenance doses of aspirin above 100 mg reduce the effectiveness of ticagrelor and should be avoided. The treatment should be avoided in patients with severe hepatic impairment, as this is likely to increase serum concentration of ticagrelor and there are no studies of the treatment in these patients. The most common adverse events (>5%) associated with the use of ticagrelor included bleeding and dyspnea.
Ticagrelor was first approved by the FDA as a blood-thinning agent in 2011 and again in September 2015 as an oral 60-mg tablet with an expanded indication for the reduction of cardiovascular risk in patients with a history of cardiovascular disease.
“In the US, someone has a stroke every 40 seconds and the impact on a person’s life can be truly devastating,” Mene Pangalos, PhD, executive vice president, BioPharmaceuticals R&D, said. “Brilinta is a well-established medicine across patients with coronary artery disease and with today’s approval, we can now expand its potential to patients with an acute ischemic stroke or transient ischemic attack.”