Twice-A-Day CLOpidogrel vs Ticagrelor to Reduce Short-Term MACE after Primary PCI: The TADCLOT Trial.

Background: The first month post-primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is the highest risk period for major adverse cardiovascular events (MACE), including stent thrombosis. Ticagrelor and double dose clopidogrel are effective antiplatelet therapies, but no head-to-head comparison exists in this setting.

Objectives: We sought to evaluate the efficacy of ticagrelor over twice daily clopidogrel in reducing MACE events within the first one month post primary PCI.

Methods: TADCLOT, a double-blind, randomized superiority trial at the National Institute of Cardiovascular Diseases, Karachi, Pakistan (February 19, 2024-January 30, 2025), randomized 2,201 patients with STEMI within 24 hours of primary PCI 1:1 to ticagrelor (180 mg loading dose, 90 mg BID) or BID clopidogrel (600 mg loading dose, 75 mg BID) for 1 month. The primary endpoint was MACE (death, myocardial infarction, stent thrombosis, stroke, or target lesion revascularization) at 1 month, analyzed by intention-to-treat. Secondary endpoints included individual MACE components and clinically significant bleeding (BARC types 2, 3, or 5).

Results: Among 2,201 randomized patients, MACE occurred in 24 (2.2%) ticagrelor patients vs. 32 (2.9%) in BID clopidogrel patients (HR 0.75; 95% CI, 0.44-1.27; P=0.28; ARD -0.7%; 95% CI, -2.05% to 0.60%). Cardiovascular death or definite stent thrombosis occurred in 21 (1.9%) vs. 27 (2.5%) patients (HR 0.77; 95% CI, 0.44-1.37). Clinically significant bleeding (BARC type 2, 3, or 5) occurred in 6 patients (0.5%) with ticagrelor versus 4 (0.4%) with clopidogrel (HR 1.50, 95% CI 0.42-5.31). Major bleeding (BARC 3 or 5) was infrequent and similar between the groups: 3 patients (0.3%) in the ticagrelor arm and 2 (0.2%) in the clopidogrel arm (HR 1.50, 95% CI 0.25-8.97). At both 7 (HR 0.15, 95% CI 0.04-0.5; p=0.002) and 14 days (HR 0.46, 95% CI 0.23-0.91; p=0.02), MACE was significantly lower with ticagrelor compared with BID clopidogrel, although these differences were no longer statistically significant at 30 days.

Conclusions: Ticagrelor was not superior to BID clopidogrel in reducing MACE at one month after primary PCI, and bleeding rates were similar. However, event rates were lower than anticipated and ticagrelor significantly reduced MACE within the first 2 weeks compared with BID clopidogrel. (ClinicalTrials.gov, NCT06318481).