Ticagrelor monotherapy after three-month dual antiplatelet therapy in patients with acute coronary syndrome: a target trial emulation

Randomized trials suggest that switching from dual antiplatelet therapy (DAPT) to ticagrelor alone after a short DAPT period reduces bleeding without increasing ischemic events. Whether this finding extends to Chinese patients with acute coronary syndrome (ACS) in routine practice remains uncertain. To emulate the TICO trial using multisite electronic health record (EHR) data from China and compare ticagrelor monotherapy after 3 months of DAPT with ticagrelor-based DAPT continued through 12 months among patients with ACS treated with drug-eluting stents by percutaneous coronary intervention (PCI). We conducted a target trial emulation using EHR data from four tertiary teaching hospitals (March 2021-June 2024). Patients aged 19–80 years who remained event-free through 90 +/- 14 days after PCI while receiving ticagrelor plus aspirin were classified as receiving monotherapy or continued DAPT. From 28,313 eligible patients, 1:5 propensity score matching yielded 5,070 patients (845 monotherapy; 4,225 DAPT). The primary outcome was net adverse clinical events (NACE), a composite of Thrombolysis in Myocardial Infarction (TIMI) major bleeding or major adverse cardiac and cerebrovascular events (MACCE). Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs); incidence rates are reported per 100 person-years (PY). Over a median 270-day follow-up (593 and 2,956 PY), NACE occurred in 66 monotherapy patients (7.81%; 11.13 per 100 PY) and 332 DAPT patients (7.86%; 11.23 per 100 PY; HR 1.00, 95% CI 0.77–1.31; P = 0.986). In exploratory analyses, monotherapy was associated with less TIMI major bleeding (2.49% vs. 4.09%; HR 0.61, 95% CI 0.39–0.97) and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding (2.25% vs. 4.40%; HR 0.50, 95% CI 0.31–0.81). MACCE was numerically more frequent (5.33% vs. 3.86%; HR 1.39, 95% CI 1.00-1.94; P = 0.051), and stroke was more frequent (1.07% vs. 0.47%; HR 2.35, 95% CI 1.06–5.18; P = 0.035; 9 vs. 20 events). Ticagrelor monotherapy after 3 months of DAPT was not associated with a difference in NACE compared with continued DAPT. Bleeding was less frequent, whereas MACCE and stroke were more frequent in exploratory analyses. Because this observational study cannot establish therapeutic equivalence and did not ascertain stroke etiology or incident atrial fibrillation, these findings require confirmation in adequately powered randomized trials.