Effectiveness and safety of prasugrel- versus clopidogrel-based dual antiplatelet therapy for acute ischemic stroke

Although dual antiplatelet therapy (DAPT) prevents early recurrence of non-cardioembolic stroke, data on prasugrel-based DAPT are limited. We aimed to compare the effectiveness and safety of prasugrel- and clopidogrel-based DAPTs in acute atherothrombotic stroke.

Using the Diagnosis Procedure Combination database from April 2020 to March 2023, we identified patients admitted with atherothrombotic stroke who received aspirin plus clopidogrel or prasugrel. We compared a favorable functional outcome at discharge, hemorrhagic complications, seven-day mortality, and readmission for atherothrombotic stroke recurrence between the groups using propensity score overlap-weighting analyses. The number needed to treat (NNT) and harm (NNH) was calculated for each effectiveness and safety measure, respectively.

Among 48,863 eligible patients (46,153 receiving clopidogrel and 2710 receiving prasugrel), the proportion of patients with a favorable functional outcome at discharge was higher in the prasugrel-based DAPT group (41.4 % vs. 40.0 %; adjusted risk difference [aRD], 1.4 %; 95 % confidence interval [CI], 0.4 %-2.4 %), corresponding to an NNT of 71. Overall hemorrhagic complications were more frequent in the prasugrel-based DAPT group (3.9 % vs. 2.4 %; aRD, 1.4 %; 95 % CI, 1.1 %-1.8 %), with an NNH of 67. No significant difference was observed in the seven-day mortality (0.50 % vs. 0.43 %; aRD, 0.07 %; 95 % CI, -0.06 %-0.21 %) or the proportion of 90-day readmissions for atherothrombotic stroke recurrence (0.91 % and 1.08 %; aRD, -0.17 %; 95 % CI, -0.37 %-0.03 %).

Prasugrel-based DAPT may improve outcomes without increasing early mortality, however, bleeding risk warrants caution. Careful patient selection is crucial for balancing ischemic benefits and bleeding risks, aiding acute-phase treatment decisions for high-risk patients.