Abstract Body (Do not enter title and authors here): Background
Dual antiplatelet therapy (DAPT) consisting of ticagrelor, a P2Y₁₂ inhibitor, and aspirin, is the recommended treatment of acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI). However, recently ticagrelor monotherapy has been shown to preserve ischemic protection while reducing bleeding risk in ACS patients. We aimed to compare the clinical outcomes of DAPT and ticagrelor monotherapy in ACS patients undergoing PCI.

Methods
MEDLINE, Scopus, and EMBASE were queried up to May 2024 for randomized controlled trials (RCTs) comparing ticagrelor monotherapy after 1 to 3 months of DAPT versus continued DAPT for 12 months in ACS patients. The primary outcomes were all-cause death, net adverse clinical events (NACE) and Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. Key secondary endpoints included BARC 3 or 5 bleeding, myocardial infarction (MI), hemorrhagic and ischemic stroke, and target vessel revascularization (TVR). A random-effects meta-analysis was performed to derive risk ratios (RR) and corresponding 95% confidence intervals (CI).

Results
Six RCTs including 28,526 patients, with a mean age of 63.5 years, were included. DAPT was associated with a significantly higher risk of all-cause death (RR: 1.32, 95% CI: 1.05-1.64, P=0.02), NACE (RR: 1.20, 95% CI: 1.01-1.42, P=0.04), and BARC 2, 3, or 5 bleeding (RR: 1.96, 95% CI: 1.71-2.26, P<0.00001) compared to monotherapy. DAPT significantly increased the risk of BARC 3 or 5 bleeding (RR: 2.06, 95% CI: 1.69-2.51, P<0.00001) however, no association was seen in myocardial infarction (RR: 1.01, 95% CI: 0.84-1.20, P=0.94). Conversely, DAPT resulted in a non-significant reduction in ischemic (RR: 0.94, 95% CI: 0.63-1.41, P=0.77) and hemorrhagic stroke (RR: 0.83, 95% CI: 0.36-1.95, P=0.67). Additionally, no significant association could be ascertained in TVR (RR: 1.18, 95% CI: 0.94-1.48, P=0.15).

Conclusion
Our analysis highlights the elevated risks of all-cause death, NACE, and major bleeding with DAPT compared to monotherapy in ACS patients post-PCI, favoring the latter for safety. Future investigations should refine antiplatelet therapy durations and identify specific patient subsets for optimal DAPT utilization.