Dual antiplatelet therapy after non-cardioembolic ischemic stroke or transient ischemic attack beyond randomized controlled trials: results from the “REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack” (READAPT - NCT05476081)

Background and aims. Dual antiplatelet therapy (DAPT) has proven superior to monotherapy in preventing early recurrent events after minor non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA) in randomized clinical trials (RCTs). However, the applicability of these results to broader real-world populations remains poorly characterized, particularly for patients with moderate stroke severity, diverse etiologies, acute reperfusion treatments, or complex comorbidities. We aimed to assess the real-world effectiveness and safety of early short-term DAPT in clinical scenarios extending beyond the eligibility criteria of landmark trials. Methods: The READAPT study is a large, prospective, multicenter, observational cohort study conducted across 64 Italian stroke centers. It enrolled patients with acute non-cardioembolic ischemic stroke or TIA who were treated with short-term DAPT in routine clinical practice, regardless of stroke severity, timing, or treatment protocols. Several pre-specified analyses were performed to evaluate the effectiveness and safety of DAPT in patient populations not represented in RCTs, including individuals with (1) mild-to-moderate ischemic stroke (National Institute of Health Stroke Scale [NIHSS] 4–10), (2) strokes due to small-artery occlusion (SAO) or large-artery atherosclerosis (LAA) , (3) those receiving intravenous thrombolysis, and (4) patients with cancer. Results: In propensity-matched comparisons, DAPT was associated with improved 90-day functional outcomes and greater early neurological improvement compared to single antiplatelet therapy (SAPT) in patients with mild-to-moderate stroke, without increased risk of intracranial hemorrhage. Women with mild-to-moderate stroke, especially at younger age, had a lower 90-day risk of vascular recurrence after DAPT compared to men. Infarct location (anterior vs. posterior circulation) did not significantly influence the safety or effectiveness of DAPT, except for slightly worse 90-day functional outcomes in posterior circulation strokes. In SAO-related stroke, short-term DAPT appeared safe and potentially beneficial. Among patients with LAA, DAPT use beyond trial boundaries was common but linked to higher bleeding risks, highlighting the need for individualized assessment. DAPT following thrombolysis was safe and associated with improved 90-day functional outcomes and fewer ischemic events compared to DAPT alone, whereas in patients with active malignancy, particularly hematological cancer, it was linked to a higher risk of both ischemic and bleeding events at 90 days. Conclusions: The READAPT study expands current knowledge on DAPT use beyond randomized trial criteria, confirming potential benefits in broader real-world populations while emphasizing the importance of careful patient selection. These findings support a more personalized approach to secondary stroke prevention with DAPT.