Tailoring Dual Antiplatelet Therapy for Stroke Prevention: A Meta-Analysis of Timing, Duration, and Stroke Subtypes

NAIF M. ALHAWITI ^1* Sherouk Fouda ² Naser D. Alotaibi ³ Hassan A. Madkhali ⁴ Fahad K. Alsharef ⁵ Ashraf El-Metwally ⁶ Jamal M Alhawiti ⁷

• ¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
• ² School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia
• ³ Department of Neurology, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia., Riyadh, Saudi Arabia
• ⁴ Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
• ⁵ College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia, Riyadh, Saudi Arabia
• ⁶ College of Public Health and Health Informatics, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
• ⁷ College of Medicine, Jouf University, Sakakah, Saudi Arabia

Background: DAPT is commonly used for secondary stroke prevention, but the optimal timing and duration of treatment remain uncertain. This meta-analysis investigated the efficacy and safety of DAPT compared to any single antiplatelet therapy in stroke patients. We examined the effectiveness of DAPT versus monotherapy, stratified by stroke type, timing of intervention onset, and duration of DAPT. We systematically searched electronic databases for RCTs comparing DAPT with any single antiplatelet therapy in stroke patients. Data from 30 RCTs involving 75,504 patients were pooled using a random-effects model. The primary outcome was the recurrent ischemic stroke. Secondary outcomes included hemorrhagic stroke, cardiovascular events, major bleeding, and mortality. Subgroup analysis examined the effectiveness of DAPT versus any single antiplatelet therapy, stratified by stroke types, timing of intervention onset (within 12, 24, 48, and 72 hours, and 7 to 180 days), and duration of DAPT (short-term: up to 30 days; long-term: beyond 30 days).Results: Compared to any single antiplatelet therapy, DAPT significantly reduced the risk of recurrent ischemic stroke (RR: 0.69; 95% CI: 0.60-0.79; I²=47%). Subgroup analyses revealed that DAPT was most effective when initiated within 12 hours (RR: 0.73; 95% CI: 0.57-0.92) and 24 hours (RR: 0.66; 95% CI: 0.52-0.84) of symptom onset. Short-term DAPT (up to 30 days) showed a greater reduction in recurrent ischemic events (RR: 0.65; 95% CI: 0.53-0.79) compared to longterm DAPT (beyond 30 days; RR: 0.72; 95% CI: 0.60-0.86). DAPT also significantly reduced the risk of cardiovascular events (RR: 0.77; 95% CI: 0.69-0.87; I²=47%). However, DAPT did not have a significant effect on hemorrhagic stroke (RR: 1.28; 95% CI: 0.80-2.07), major bleeding (RR: 1.10; 95% CI: 0.91-1.33; I²=45%), or mortality (RR: 1.01; 95% CI: 0.88-1.15; I²=27%).DAPT is effective in reducing recurrent ischemic stroke and cardiovascular events compared to monotherapy. The greatest benefit appears to be associated with early initiation (within 24 hours) and short-term treatment (up to 30 days). These findings support the use of DAPT in secondary stroke prevention, with consideration for individualized treatment strategies based on timing and duration. Further research is needed to optimize DAPT protocols and explore its role in specific stroke subtypes.