In addition to showing significant and clinically meaningful reduction in acute ischemic stroke and transient ischemic attack, ticagrelor showed a consistent safety profile to what has been observed in previous trials.
Results from the phase 3 THALES trial (NCT03354429) demonstrated that treatment with ticagrelor (Brilinta; AstraZeneca) lowers the risk of the composite of stroke or death among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (AIS) or transient ischemic attack (TIA) who were not undergoing intravenous or endovascular thrombosis.1,2
Patients who were administered 90-mg ticagrelor twice daily with aspirin saw a reduction in the rate of the primary composite end point of stroke and death by 17% (hazard ratio [HR], 0.83; 95% CI, 0.71—0.96; P = .02) compared to aspirin alone.
THALES comprised of 11,016 patients who were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90-mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily; n = 5523) or matching placebo plus aspirin (n = 5493).
“Patients who had an acute ischemic stroke or transient ischemic attack may experience a subsequent, potentially avoidable stroke. Results from the phase 3 THALES trial confirm that aspirin plus Brilinta has the potential to be a new effective treatment option for these high-risk patients and we look forward to continuing discussions with regulatory authorities,” Mene Pangalos, PhD, executive vice president, BioPharmaceuticals R&D, AstraZeneca, said in a statement.
The primary outcome, a compositive of stroke or death within 30 days, occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group. Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (HR, 0.79; 95% CI, 0.68—0.93; P = .004).
The other secondary outcome of overall disability, measured as >1 on the modified Rankin Scale (mRS) occurred in 23.8% of the patients in the ticagrelor-aspirin group and in 24.1% of the patients in the aspirin group (odds ratio [OR], 0.98; 95% CI, 0.89—1.07; P = .61). Disabling stroke, measured as mRS score >2, occurred in 2.7% of the patients in the ticagrelor-aspirin group and in 3.5% of the patients in the aspirin group.
Researchers found that severe bleeding, the primary safety end point of the study, occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 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.
Overall, the safety results were consistent with those of the primary intention-to-treat analysis. Premature permanent discontinuation of trial treatment owing to bleeding accounted for 152 patients (2.8%) in the ticagrelor-aspirin group and 32 (0.6%) in the aspirin group.
Results of the trial come less than a week after AstraZeneca announced that the FDA had accepted its supplemental new drug application (sNDA) and granted priority review designation for ticagrelor for the reduction of subsequent stroke in patients who experienced an acute ischemic stroke (AIS) or transient ischemic attack (TIA). The decision was made based on the results of THALES.3 The Prescription Drug User Fee Act date for ticagrelor is scheduled for the fourth quarter of 2020.
Ticagrelor is a long history with the FDA, becoming approved as a blood-thinning agent in 2011 and again in September 2015 as an oral 60-mg tablet for an expanded indication for the reduction of cardiovascular risk in patients with a history of cardiovascular disease.4 Most recently, the treatment became FDA approved for the reduction of risk for first heart attack or stroke in patients with coronary artery disease (CAD) in June. It became the first regulatory approval for aspirin plus ticagrelor in those who are high risk but have no history of heart attack or stroke.5
1. BRILINTA significantly reduced the rate of the composite of stroke and death in patients who had an acute ischemic stroke or transient ischemic attack in the phase 3 THALES trial [news release]. Wilmington, DE. AstraZeneca. Published July 16, 2020. Accessed July 16, 2020. astrazeneca-us.com/content/az-us/media/press-releases/2020/brilinta-significantly-reduced-the-rate-of-the-composite-of-stroke-and-death-in-patients-who-had-an-acute-ischemic-stroke-or-transient-ischemic-attack-in-the-phase-iii-thales-trial-07162020.html
2. Johnson CS, Amarenco P, Denison H, et al. Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA. N Engl J Med. Published June 16, 2020. doi: 10.1056/NEJMoa1916870.
3. Brilinta granted FDA priority review for the reduction of subsequent stroke in patients who had an acute ischemic stroke or transient ischemic attack [news release]. Wilmington, DE. AstraZeneca. Published July 9, 2020. Accessed July 16, 2020. astrazeneca-us.com/content/az-us/media/press-releases/2020/brilinta-granted-fda-priority-review-for-the-reduction-of-subsequent-stroke-in-patients-who-had-an-acute-ischemic-stroke-or-transient-ischemic-attack-07082020.html.
4. BRILINTA Approved in the US to Reduce the Risk of a First Heart Attack or Stroke in High-Risk Patients with Coronary Artery Disease [news release]. Wilmington, DE. AstraZeneca. Published June 1, 2020. Accessed July 16, 2020. businesswire.com/news/home/20200601005200/en/BRILINTA-Approved-Reduce-Risk-Heart-Attack-Stroke
5. BRILINTA Approved in the US to Reduce the Risk of a First Heart Attack or Stroke in High-Risk Patients with Coronary Artery Disease [news release]. Wilmington, DE. AstraZeneca. Published June 1, 2020. Accessed July 16,