Abstract 4144782: Identifying Factors Influencing Response to Dual Antiplatelet Therapy in Non-Cardioembolic Ischemic Stroke and Transient Ischemic Attack: A Meta-analysis of Randomized Controlled Trials

Background: While dual antiplatelet therapy (DAPT) has been shown to significantly decrease recurrent stroke in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of non-cardioembolic origin, it comes with a substantial increase in the risk of bleeding. Research Question: Do all patients with non-cardioembolic, mild ischemic stroke/high-risk TIA derive benefits from DAPT for secondary prevention? Aims: To identify patients who derive attenuated benefit from DAPT to avoid excessive bleeding risk. Methods: We searched 6 databases from inception to May 10, 2024 to identify randomized-controlled trials (RCTs) comparing short-term DAPT (up to 3 months) with aspirin for secondary prevention of non-cardioembolic ischemic stroke or TIA. The primary efficacy outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of any stroke, myocardial infarction, and cardiovascular (CV) death, with prespecified subgroups based on participants’ pre-stroke treatment with statins and antiplatelet agents. Secondary efficacy outcomes comprised of recurrent ischemic events and hemorrhagic stroke. Safety outcomes included major bleeding, CV mortality, and all-cause mortality. A random-effects meta-analysis was performed using restricted maximum likelihood method. Results: There were 5 RCTs including 27,559 patients. In the unselected population, DAPT significantly reduced MACCE (RR, 0.78; 95% CI, 0.71 to 0.85; I 2 = 0%; Figure 1A), compared to aspirin. However, patients with baseline statin (RR, 0.93; 95% CI, 0.73 to 1.17; I 2 = 0%; Figure 1A) or antiplatelet (RR, 0.91; 95% CI, 0.69 to 1.21; I 2 = 0%; Figure 1A) before index events did not derive benefits from DAPT. While DAPT led to significantly lower recurrent ischemic stroke (RR, 0.74; 95% CI, 0.68 to 0.81; I 2 = 0%; Figure 1B), it resulted in a significantly higher risk of hemorrhagic stroke, major bleeding, and intracerebral hemorrhage, compared to aspirin (Figure 1B). Moreover, the use of DAPT trended toward an increased risk of all-cause and CV mortality (Figure 1B). Conclusions: Patients with baseline statin/antiplatelts use may not derive the same benefits from DAPT for secondary prevention of non-cardioembolic ischemic stroke or TIA.