Ticagrelor Plus Aspirin Dual Antiplatelet Therapy Benefits Moderate Ischemic Stroke

Clay Johnston, MD, PhD

An exploratory analysis of the THALES clinical trial (NCT03354429) showed that patients with moderate ischemic stroke consistently benefitted from a dual antiplatelet therapy, or DAPT, of ticagrelor (Brilinta; AstraZeneca) plus aspirin compared to patients with less severe ischemic stroke, with no increased safety concerns.¹

Ticagrelor previously received FDA approval in November 2020 to reduce the risk of stroke in patients with acute ischemic stroke (AIS) or high-risk transient ischemic attack (TIA).² The THALES trial was the basis for the approval, in which approximately 30% of the patient population had National Institutes of Health Stroke Scale (NIHSS) scores between 4 to 5.

In this analysis, senior author Clay Johnston, MD, PhD, dean, Dell Medical School, University of Texas at Austin, and colleagues, evaluated 3312 patients with moderate stroke (baseline NIHSS score of 4 to 5), and 6671 patients with less severe stroke (NIHSS score of 0 to 3). Ticagrelor 180-mg loading dose on day 1 followed by 90 mg twice daily on days 2 to 30 or placebo were given 24 hours after symptom onset while all patients received aspirin, 300 mg to 325 mg, on day 1 followed by aspirin, 75 mg to 100 mg, daily on days 2 to 30.

The primary outcome, time to stroke or death within 30 days, was observed in 7.6% of patients with moderate stroke (129 of 1671) for those in the ticagrelor group and 9.1% (150 of 1641) for those in the placebo group (hazard ratio [HR], 0.84 [95% CI, 0.66-1.06]). Additionally, the primary outcome event rate in patients with less severe stroke was 4.7% (158 of 3359) for those in the ticagrelor group and 5.7% (190 of 3312) for those in the placebo group (HR, 0.82 [95% CI, 0.66-1.01];P for interaction = .88).

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Among those with moderate stroke, the primary safety end point, GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) severe bleeding, occurred in 8 patients (0.5%) in the ticagrelor group and 4 patients (0.2%) in the placebo group (HR, 1.97 [95% CI, 0.59-6.53]; risk difference, 0.24% [95% CI, –0.18 to 0.65]), with a number needed to harm (NNH) of 425 to produce 1 severe bleeding within 30 days. For those with an NIHSS score of 0 to 3, the primary safety end point occurred in 16 patients (0.5%) in the ticagrelor group and 3 patients (0.1%) in the placebo group (risk difference, 0.39% [95% CI, 0.13-0.64]), with a NNH of 259 (P for interaction = .26).

At day 30, the proportion of overall disability, indicated by modified Rankin Scale (mRS) score greater than 1, was greater in patients with moderate stroke compared with those with less severe stroke (37.2% [612 of 1643] vs 18.8% [620 of 3299] in the ticagrelor group; 37.6% [609 of 1619] vs 19.4% [627 of 3236] in the placebo group). In patients with moderate stroke, a subsequent disabling stroke up to day 30 occurred in 90 of 1667 patients (5.9%) in the ticagrelor group and in 115 of 1637 patients (7.0%) in the placebo group (odds ratio, 0.83 [95% CI, 0.63-1.10]), with a number needed to treat of 91 to avoid 1 disabling stroke at day 30.

"Although the risk of disability is higher overall in patients with stroke with a baseline NIHSS score of 4 to 5 owning to greater severity of the index event, DAPT with ticagrelor and aspirin reduced the number of patients with subsequent disabling stroke,” Johnston et al wrote.

Previously reported data from THALES showed that patients with a mild-to-moderate AIS or TIA who were not undergoing intravenous or endovascular thrombosis saw a reduction in the rate of the primary composite end point of stroke and death by 17% (HR, 0.83 [95% CI, 0.71-0.96]; P = .02) compared to aspirin alone.²

Naeem Khan, MD, vice president of AstraZeneca’s Cardiovascular and Metabolic Diseases Portfolio, sat down with NeurologyLive following the first data readout in July 2020. In the video below, he discussed the trial in further detail and provided an overview on why ticagrelor has a unique path among other stroke treatments.

REFERENCES

1. Wang Y, Pan Y, Li H, et al. Efficacy and safety of ticagrelor and aspirin in patients with moderate ischemic stroke: an exploratory analysis of the THALES randomized clinical trial. JAMA Neurol. Published online July 9, 2021. doi: 10.1001/jamaneurol.2021.2440

2. Brilinta approved in the US to reduce the risk of stroke in patients with an acute ischemic stroke or high-risk transient ischemic attack. News release. AstraZeneca. November 6, 2020. Accessed July 20, 2020. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2020/brilinta-approved-in-the-us-to-reduce-the-risk-of-stroke-in-patients-with-an-acute-ischemic-stroke-or-high-risk-transient-ischemic-attack-11062020.html