P2Y12i plus aspirin reduces composite of recurrent stroke or death in stroke patients
Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIALiterature - Johnston SC, Amarenco P, Denison H, et al. - N Engl J Med 2020;383:207-17. DOI: 10.1056/NEJMoa1916870
Introduction and methods
No benefit of ticagrelor alone vs. aspirin on prevention of subsequent CV events was observed in patients with acute ischemic stroke or TIA . Findings from exploratory analyses suggest that a subgroup of patients who had received aspirin 7 days prior to randomization and were subsequently randomized to ticagrelor may benefit from this treatment strategy . Therefore, a combination of ticagrelor and aspirin was investigated for the prevention of subsequent stroke or death. Risk of recurrent stroke is highest in the first month after an acute ischemic stroke or TIA [1,3], therefore, a 30-day treatment period was considered to be appropriate for this study.
The Acute Stroke or Transient Ischaemic Attack Treated with Ticagrelor and ASA (acetylsalicylic acid) for Prevention of Stroke and Death (THALES) trial was performed to examine whether 30-day treatment with ticagrelor and aspirin is superior to aspirin alone in reducing risk of subsequent stroke or death in patient with acute noncardioembolic cerebral ischemia. It was a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Eligible patient had either a mild-to-moderate acute noncardioembolic ischemic stroke (91% of patients) or a high-risk TIA (9% of patients). 5523 Patients were randomized to receive ticagrelor plus aspirin and 5493 to matching placebo plus aspirin within 24 hours after onset of symptoms. Exclusion criteria were planned intravenous or intraarterial thrombolysis or mechanical thrombectomy within 24 hours before randomization or planned use of anticoagulation of specific antiplatelet therapy other than aspirin. Bleeding events were classified as severe, moderate or mild according to definitions in the GUSTO trial. Primary outcome was a composite of stroke or death. Stroke included ischemic stroke, hemorrhagic stroke and stroke of undetermined type. Primary safety outcome was first severe bleeding event, a composite of first intracranial hemorrhage or fatal bleeding event.
- Primary outcome occurred less often in the ticagrelor plus aspirin group (5.5%) compared to the aspirin group (6.6%) (HR 0.63, 95%CI: 0.71-0.96, P=0.02).
- First secondary outcome of subsequent ischemic stroke occurred less often in the ticagrelor plus aspirin group (5.0%) compared to the aspirin group (6.3%) (HR 0.79, 95%CI: 0.68-0.93, P=0.004). Secondary outcomes of overall disability (score >1 on the modified Rankin scale) occurred in 23.8% of patients in the ticagrelor plus aspirin group and in 24.1% of the patients in the aspirin group (OD 0.98, 95%CI: 0.89-1.07, P=0.61).
- Primary safety outcome event (severe bleeding) occurred in 28 patient (0.5%) in the ticagrelor plus aspirin group and in 7 patients (0.1%) in the aspirin group (HR 3.99, 95%CI: 1.74-9.14, P=0.001).
- Composite outcome event of intracranial hemorrhage or fatal bleeding occurred in 22 patients (0.4%) in the ticagrelor plus aspirin group and in 6 patients (0.1%) in the aspirin group. Intracranial hemorrhage occurred in 20 patients (0.4%) in the ticagrelor plus aspirin group and in 6 patients (0.1%) in the aspirin group. Fatal bleeding occurred in 11 patients (0.2%) in the ticagrelor plus aspirin group and 2 patients (<0.1%) in the aspirin group.
- Discontinuation rate due to bleeding was 2.8% (152 patients) in ticagrelor plus aspirin group and 0.6% (32 patients) in the aspirin group. Discontinuation rate because of dyspnea was 1.0% in the ticagrelor plus aspirin group and 0.2% in the aspirin group. These events accounted for the entire between-group difference in discontinuation rate.
A combination of ticagrelor and aspirin compared to aspirin alone resulted in a reduction of recurrent stroke or death in patients with mild-to-moderate stroke or TIA after 30 days. Severe bleeding was increased in those on ticagrelor and aspirin compared to aspirin alone.