BACKGROUND: Dual antiplatelet therapy (DAPT) for 1 year after acute coronary syndrome (ACS) in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is the standard of care. However, it is associated with a higher incidence of bleeding events. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the safety and efficacy of short-term DAPT. AIMS: This study aimed to assess the relative risk of major and minor bleeding, net adverse clinical and cerebral events (NACCE), and all-cause mortality in patients with ACS undergoing PCI with DES, comparing ticagrelor-based short-term DAPT (≤ 3 months) followed by ticagrelor monotherapy for up to 12 months versus 12-month DAPT. The secondary endpoint evaluated the relative risk of complications, including myocardial infarction, stroke, stent thrombosis, repeat revascularization, and cardiovascular mortality. METHODS: A systematic search of PubMed, Scopus, and Cochrane Central was conducted for eligible RCTs. A subgroup analysis of ultrashort-term DAPT (≤ 1 month) followed by ticagrelor monotherapy for up to 12 months was also performed. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Five RCTs were included with a total of 21,407 patients. Short-term DAPT was associated with a significant reduction in major bleeding (RR 0.50
95% CI 0.38-0.66
p <
0.01), minor bleeding (RR 0.53
95% CI 0.35-0.80
p <
0.01), NACCE (RR 0.71
95% CI 0.59-0.85
p <
0.01), and all-cause mortality (RR 0.78
95% CI 0.62-0.98
p =0.04). CONCLUSIONS: Short-term DAPT followed by ticagrelor monotherapy up to 12 months was associated with a significant reduction in major and minor bleeding, NACCE, and all-cause mortality compared to 12-month DAPT. There were no significant differences in myocardial infarction, stroke, stent thrombosis, repeat revascularization, or cardiovascular mortality. Major bleeding and NACCE remained consistently reduced in the subgroup analysis.