Aspirin combined with ticagrelor or clopidogrel may help reduce stroke risk

Dual antiplatelet therapy that combined aspirin with either ticagrelor or clopidogrel outperformed aspirin alone in minor ischemic stroke and transient ischemic attack, according to results of a network meta-analysis.

However, researchers reported no statistically significant difference between the two regimens for the primary outcome of a composite of recurrent stroke or death up to 90 days.“Multiple clinical trials established the superior efficacy of short-term dual antiplatelet therapy (DAPT) with clopidogrel and aspirin compared with antiplatelet monotherapy for secondary stroke prevention following minor stroke or TIA,” Ronda Lun, MD, of the University of Ottawa School of Epidemiology and Public Health in Canada, and colleagues wrote. “This led to revised guideline recommendations from multiple organizations, including the American Heart Association Guidelines for the Prevention of Stroke in Patients With Stroke and TIA and the Heart and Stroke Foundation of Canada Stroke Best Practice Recommendations for Stroke Prevention.

“Subsequently, the recent publication of the Acute Stroke or Transient Ischaemic Attack Treated with Ticagrelor and ASA [acetylsalicylic acid] for Prevention of Stroke and Death (THALES) trial in 2020 demonstrated similar results using an alternative DAPT regimen; the combination of ticagrelor and aspirin was also superior to aspirin monotherapy in reducing the risk of stroke or death,” they added.

To the researchers’ knowledge, no large randomized clinical trials have directly compared these two DAPT regimens. In the current study, they searched three databases between inception and February 2021 for randomized clinical trials with adults with acute minor ischemic stroke or TIA that included those that provided the two DAPT interventions within 72 hours of symptoms and had at least 30 days of follow-up. They included five trials with 22,098 patients overall, of whom 5,517 were in the clopidogrel and aspirin arm, 5,859 were in the ticagrelor and aspirin arm and 10,722 were in the aspirin arm. In addition to the aforementioned primary outcome, for which they performed a sensitivity analysis at 30 days, Lun and colleagues examined major bleeding, mortality, adverse events and functional disability as secondary outcomes.

Results showed superiority for clopidogrel and aspirin (HR = 0.74; 95% credible interval [CrI], 0.64-0.84) and ticagrelor and aspirin (HR = 0.79; 95% CrI, 0.68-0.91) compared with aspirin for preventing recurrent stroke and death. Clopidogrel and aspirin showed no statistically significant difference compared with ticagrelor and aspirin (HR = 0.94; 95% CrI, 0.78-1.13). The researchers noted higher rates of major hemorrhage for both DAPT regimens compared with aspirin alone. Further, they reported an association between clopidogrel and aspirin and decreased risk for functional disability compared with aspirin alone (HR = 0.82; 95% CrI, 0.74-0.91) and ticagrelor and aspirin (HR = 0.85; 95% CrI, 0.75-0.97).

“Our study suggests aspirin and ticagrelor is a reasonable alternative to aspirin and clopidogrel where there is clopidogrel failure or intolerance,” Lun and colleagues wrote.