Dual treatment with ticagrelor and aspirin effective for moderate ischemic stroke beyond aspirin monotherapy

1. Dual treatment with ticagrelor and aspirin is both safe and effective for patients with moderate ischemic stroke, beyond the benefits of aspirin monotherapy

Evidence Rating Level: 2 (Good)

Study Rundown: Dual antiplatelet therapy (DAPT) is a well-studied approach to the treatment of ischemic stroke and transient ischemic attack (TIA). Studies investigating various combinations with aspirin have demonstrated that early, short-term DAPT should be recommended for those at high risk for TIA and minor noncardioembolic ischemic stroke. Many of these studies, however, have not included participants with moderate ischemic stroke. The THALES trial included this group for a specific medication combination but did not report on the safety and efficacy of DAPT among those with moderate ischemic stroke.

This exploratory post-hoc analysis of the THALES trial sought to explore dual antiplatelet therapy with ticagrelor and aspirin for patients with moderate acute ischemic stroke. This combination demonstrated similar safety and efficacy to aspirin monotherapy among this population, as well as those with less severe ischemic cerebrovascular events.

Overall, this study suggests that combination treatment with ticagrelor and aspirin is both safe and effective for patients with moderate ischemic stroke, beyond the benefits of aspirin monotherapy. This DAPT also appears to reduce the number of stroke patients who are subsequently disabled, compared to aspirin alone. Limitations include small sample sizes with respect to safety outcomes and bleeding events.

Click to read the study in JAMA Neurology

Relevant Reading: Guidelines for the Early Management of Patients With Acute Ischemic Stroke

In-Depth [ retrospective cohort]:

DAPT as an early, 21-day treatment for those at risk for TIA and ischemic stroke is currently recommended. The Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES) randomized clinical trial focused on the combination of ticagrelor and aspirin. However, the reported benefits of this combination compared to aspirin alone for those at risk for stroke did not include safety and efficacy results among those with moderate ischemic stroke. As a gap in the literature, this exploratory study aimed to discuss DAPT safety among those with moderate ischemic stroke.

The THALES trial took place at 414 hospitals in 28 countries, between January 2018 and December 2019. Patients with a NIHSS score greater than 5 and those with TIA were excluded. Patients were randomized to placebo or 180mg loading on Day 1 and 90mg bid through Day 30, all starting within 24 hours of symptom onset. All participants were given aspirin 300-325mg on Day 1 and 75-100mg for Days 2 through 30, followed by another 30-day observation period. The primary outcome was stroke or death within 30 days, as well as time to severe bleeding. A total of 3,312 patients had moderate stroke (M [SD] age = 64.5 [10.8] years, 39.0% female) and 6,671 presented with a less severe stroke (M [SD] age = 64.8 [11.2] years, 37.7% female). Among those with moderate ischemic stroke, the primary outcome event rate was 7.6% for the ticagrelor group and 9.1% for the placebo group (HR = 0.84, 95% CI 0.66 to 1.06). For those who had less severe strokes, the primary outcome event rate for ticagrelor was 4.7% compared to 5.7% in the placebo group (HR = 0.82, 95% CI 0.66 to 1.01, p interaction = 0.88). In terms of safety outcomes for those with moderate stroke, severe bleeding occurred in 0.5% of the ticagrelor group compared to 0.2% of the placebo group (HR = 1.97, 95% CI 0.59 to 6.53, risk difference = 0.24%, 95% CI -0.18 to 0.65). For those with less severe stroke, severe bleeding occurred in 0.5% of the ticagrelor group and 0.1% of the placebo group (risk difference = 0.39%, 95% CI 0.13 to 0.64, p interaction = 0.26)

Image: PD

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