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The US Food and Drug Administration (FDA) has expanded the approved use of the antiplatelet agent ticagrelor (Brilinta).
The FDA first approved ticagrelor in 2011 to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS).
Now, the agency has approved a 60 mg dose that can be used long-term. The 60 mg tablet is expected to be available in pharmacies by the end of this month.
The recommended dosing for ticagrelor is a loading dose of 180 mg, followed by 90 mg twice daily during the first year after the ACS event. The drug is combined with aspirin, typically at a loading dose of 325 mg, followed by a daily maintenance dose of 75-100 mg.
After 1 year, patients can now receive ticagrelor at 60 mg twice daily.
The expanded indication for ticagrelor has been approved under FDA Priority Review, a designation granted to medicines with the potential to provide significant improvements in the treatment, prevention, or diagnosis of a disease.
Ticagrelor has been approved in more than 100 countries and is included in 12 major ACS treatment guidelines globally. The drug is under development by AstraZeneca.
Trial results
The FDA’s expanded approval of ticagrelor is based on results of the PEGASUS TIMI-54 trial, a large-scale study involving more than 21,000 patients.
Investigators compared ticagrelor (at 60 mg or 90 mg) plus low-dose aspirin to placebo plus low-dose aspirin in patients who had experienced a heart attack 1 to 3 years prior to study enrollment.
The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, or stroke. And the investigators found that patients in either ticagrelor arm were significantly less likely to achieve this endpoint.
At 3 years, the proportion of patients meeting the endpoint was 7.85% in the 90 mg group, 7.77% in the 60 mg group, and 9.04% in the placebo group (P=0.008 for 90 mg vs placebo and P=0.004 for 60 mg vs placebo).
Patients receiving ticagrelor also had a significantly higher incidence of major bleeding and dyspnea. The rate of TIMI major bleeding was 2.60% in the 90 mg group, 2.30% in the 60 mg group, and 1.06% in the placebo group (P<0.001 for each ticagrelor dose vs placebo).
The rate of dyspnea was 18.93% in the 90 mg group, 15.84% in 60 mg group, and 6.38% in the placebo group (P<0.001 for both comparisons). The rate of dyspnea leading to treatment discontinuation was 6.5% in the 90 mg group, 4.55% in the 60 mg group, and 0.79% in the placebo group (P<0.001 for both).
