On June 1, 2020, the FDA announced the approval of an expanded indication of ticagrelor, an oral, reversible, direct-acting P2Y12 receptor antagonist for reducing the risk of a first myocardial infarction (MI) or stroke in high-risk patients with coronary artery disease (CAD). This is the first regulatory approval for aspirin plus ticagrelor dual-antiplatelet therapy in patients who have a high cardiovascular (CV) risk without a history of heart attack or stroke.
The approval was based on data from the multinational, double-blind, placebo-controlled phase III THEMIS trial that compared the effects of ticagrelor plus aspirin to placebo plus aspirin in 19,220 patients aged ≥50 years with CAD and type 2 diabetes and no prior history of MI or stroke. The primary endpoint was the composite of first occurrence of CV death, MI, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria.
In the THEMIS trial, results demonstrated that ticagrelor was superior to placebo in reducing the incidence of CV death, MI, or stroke at a median follow-up of 39.9 months (7.7% vs. 8.5%, respectively; hazard ratio [HR] 0.90; 95% CI, 0.81-0.99; P = .04). As for safety, treatment with ticagrelor was associated with a higher incidence of TIMI major bleeding (2.2% vs. 1.0% for placebo; HR 2.32; 95% CI, 1.82-2.94; P <.001) and intracranial hemorrhage (0.7% vs. 0.5% for placebo; HR 1.71; 95% CI, 1.18-2.48; P = .005). However, there was no considerable variation between groups with regard to fatal bleeding (0.2% in the ticagrelor group vs .0.1% in the placebo group; HR 1.90; [95% CI, 0.87-4.15]; P =.11).
In a press release, Deepak L. Bhatt, MD, MPH, THEMIS trial co-chair, executive director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “The addition of ticagrelor to aspirin offers a new therapeutic option to decrease the likelihood of both heart attack and stroke, a significant advance in our ability to treat these high-risk patients.”
Earlier this year, the manufacturer announced positive findings from the phase III THALES trial, which investigated ticagrelor plus aspirin in patients with minor acute ischemic stroke or high-risk transient ischemic attack in the 24 hours prior to treatment initiation. Results revealed that treatment with ticagrelor led to a statistically substantial and clinically meaningful decline in the risk of the primary composite endpoint of stroke and death, compared with aspirin alone.
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