Twice-Daily Clopidogrel vs Ticagrelor to Reduce Short-Term Major Adverse Cardiovascular Events After Primary Percutaneous Coronary Intervention: The TADCLOT Trial

Abstract

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

Objectives: The authors sought to evaluate the efficacy of ticagrelor over twice-daily clopidogrel in reducing MACE events within the first 1 month postprimary PCI.

Methods: TADCLOT (Twice-A-Day CLOpidogrel vs Ticagrelor), a double-blind, randomized superiority trial at the National Institute of Cardiovascular Diseases, Karachi, Pakistan (February 19, 2024 to 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 twice a day) or twice-daily clopidogrel (600-mg loading dose, 75 mg twice a day) for 1 month. The primary endpoint was MACEs (death, myocardial infarction, stent thrombosis, stroke, or target lesion revascularization) at 1 month, analyzed by intention to treat. Secondary endpoints were individual MACE components and clinically significant bleeding (Bleeding Academic Research Consortium [BARC] type 2, 3, or 5).

Results: Among 2,201 randomized patients, MACEs occurred in 24 (2.2%) ticagrelor patients vs 32 (2.9%) in twice-daily clopidogrel patients (HR: 0.75; 95% CI: 0.44-1.27; P = 0.28; absolute risk difference: -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 vs 4 (0.4%) with clopidogrel (HR: 1.50; 95% CI: 0.42-5.31). Major bleeding (BARC type 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), MACEs were significantly lower with ticagrelor compared with twice-daily clopidogrel, although these differences were no longer statistically significant at 30 days.

Conclusions: Ticagrelor was not superior to twice-daily clopidogrel in reducing MACEs at 1 month after primary PCI, and bleeding rates were similar. However, event rates were lower than anticipated, and ticagrelor significantly reduced MACEs within the first 2 weeks compared with twice-daily clopidogrel. (TADCLOT-a Double Blind Randomized Controlled Trial [TADCLOT]; NCT06318481).

Keywords: acute myocardial infarction; adverse events; antiplatelet therapy; stent thrombosis.