Stroke

Aspirin plus Ticagrelor for mild stroke or TIA?

The THALES study investigated dual antiplatelet therapy with Aspirin plus Ticagrelor in patients with mild non-cardioembolic stroke or high-risk TIA.

The CHANCE and POINT trials (published in 2013 and 2018) compared the combination treatment of Aspirin and Clopidogrel to Aspirin alone for three months in patients with mild stroke or high-risk TIA and indicated benefits of the combination treatment, showing a reduction of recurrent ischemic strokes, especially within the first 21 days.

THALES, a recently published randomized-controlled multicentre trial sponsored by AstraZeneca, has now compared a 30-day course of dual antiplatelet therapy with Aspirin plus Ticagrelor to Aspirin plus placebo in patients with non-cardioembolic mild stroke (NIHSS ≤5) or high-risk TIA. Patients were excluded if they were treated with thrombolysis. A total of 11016 patients in 414 sites were randomized in this trial, treatment was assigned without 24 hours of symptom onset.

Among included patients, the median age was 65, about 39% of patients were female, White and Asian ethnicities were predominant and most included patients had an ischemic stroke (opposed to 9% with a high-risk TIA). The two treatment groups were well matched regarding baseline characteristics.

The study found a reduction of the primary endpoint (stroke or death within 30 days) in patients treated with Aspirin plus Ticagrelor (5.4% vs 6.5%, p=0.02). However, overall disability (modified Rankin Scale scores of 2-6 after 30 days) was not different between the treatment groups. Severe bleeding of any sort and intracranial haemorrhage occurred more frequently in patients treated with Aspirin plus Ticagrelor (0.5% vs. 0.1%, p=0.001 and 0.4% vs. 0.1%, p=0.005). Patients treated with Aspirin plus Ticagrelor more frequently discontinued the study medication because of bleeding (2.8% vs. 0.6%, p<0.001) and mortality was slightly (but non-significantly) higher in that treatment group (36 vs 27 deaths).

In other words, for every 1000 patients who were treated with Aspirin plus Ticagrelor compared to Aspirin plus Placebo for 30 days, 12.5 ischemic strokes were avoided (number needed to treat: 80), but 3.8 additional intracranial haemorrhages occurred (number needed to harm: 263).

It is difficult to make a direct comparison between dual antiplatelet therapies with Aspirin plus Ticagrelor and Aspirin plus Clopidogrel (studied in the CHANCE and POINT trials in similar settings), but the editorial accompanying the THALES study noted that when examining data from those three trials, there might be advantages for Aspirin plus Clopidogrel regarding reduction of ischemic stroke recurrence and smaller bleeding risk. However, a trial directly comparing those two treatment strategies would be necessary to provide clear insights.

In conclusion, while a dual antiplatelet therapy with Aspirin plus Ticagrelor for 30 days in patients with mild non-cardioembolic stroke or high-risk TIA led to a moderate reduction of recurrent strokes compared to treatment with Aspirin alone, there was an increased risk of severe bleeding and disability was not different between both treatment groups. Potential benefits and adverse effects of the combination of Ticagrelor and Aspirin need to be balanced carefully by clinicians.

Key Points:

- THALES was a randomized-controlled trial comparing Aspirin plus Ticagrelor to Aspirin plus placebo for 30 days after mild non-cardioembolic stroke or high-risk TIA

- The primary outcome, stroke or death within 30 days, was moderately decreased in the Ticagrelor-Aspirin group.

- However, the risk of severe bleeding was increased in the Ticagrelor-Aspirin group and disability was not different between both treatment groups.

 

References:

Yang P, Zhang Y, Zhang L, et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N Engl J Med. 2020 Jul 16;383(3):207-217. https://pubmed.ncbi.nlm.nih.gov/32668111/

 

Rothwell P. Antiplatelet Treatment to Prevent Early Recurrent Stroke. N Engl J Med. 2020 Jul 16;383(3):276-278. https://pubmed.ncbi.nlm.nih.gov/32668118/