The first month following primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is a period of high risk for major adverse cardiovascular events (MACEs). The TADCLOT trial aimed to compare the efficacy of ticagrelor against a twice-daily clopidogrel regimen in this critical short-term window.¹
The TADCLOT (Twice-A-Day CLOpidogrel vs Ticagrelor) study was a double-blind, randomised superiority trial conducted in Karachi, Pakistan. The trial enrolled 2,201 patients presenting with STEMI who had undergone primary PCI within the previous 24 hours.
Participants were randomised 1:1 to receive either ticagrelor (180 mg loading dose, followed by 90 mg twice daily) or twice-daily clopidogrel (600 mg loading dose, followed by 75 mg twice daily) for one month. The use of a double-dose clopidogrel regimen has been explored previously, notably in the CURRENT-OASIS 7 trial.²
The primary endpoint was the incidence of MACE (a composite of death, myocardial infarction, stent thrombosis, stroke, or target lesion revascularisation) at one month. Secondary endpoints included the individual components of MACE and clinically significant bleeding, defined as Bleeding Academic Research Consortium (BARC) type 2, 3, or 5.
The trial did not meet its primary endpoint of superiority for ticagrelor. At one month, MACE occurred in 24 patients (2.2%) in the ticagrelor group compared to 32 patients (2.9%) in the twice-daily clopidogrel group (HR: 0.75; 95% CI: 0.44–1.27; p=0.28).
Rates of clinically significant bleeding (BARC type 2, 3, or 5) were low and similar between the groups, occurring in six patients (0.5%) receiving ticagrelor and four patients (0.4%) receiving clopidogrel. Major bleeding (BARC type 3 or 5) was also infrequent and comparable (0.3% vs 0.2%, respectively).
Interestingly, an early benefit was observed with ticagrelor. The incidence of MACE was significantly lower in the ticagrelor arm at both 7 days (HR: 0.15; p=0.002) and 14 days (HR: 0.46; p=0.02). However, this difference did not remain statistically significant by the 30-day follow-up.
The TADCLOT trial found that ticagrelor was not superior to a twice-daily clopidogrel regimen for reducing MACE at one month post-primary PCI for STEMI, with both strategies demonstrating similar safety profiles. The authors concluded that while the primary endpoint was not met, “ticagrelor significantly reduced MACEs within the first 2 weeks compared with twice-daily clopidogrel.”¹ This suggests a potential early, but not sustained, benefit for ticagrelor in the immediate post-procedural period.
References
1. Hakeem A, Shah JA, Kumar R, et al. Twice-Daily Clopidogrel vs Ticagrelor to Reduce Short-Term Major Adverse Cardiovascular Events After Primary Percutaneous Coronary Intervention: The TADCLOT Trial. J Am Coll Cardiol. 2025;86(23):2330-2345. https://doi.org/10.1016/j.jacc.2025.08.041
2. Mehta SR, Tanguay JF, Eikelboom JW, et al. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet. 2010;376(9748):1233-1243. https://doi.org/10.1016/S0140-6736(10)61088-4
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