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Twice-Daily Clopidogrel vs Ticagrelor to Reduce Short-Term Major Adverse Cardiovascular Events After Primary
Abdul Hakeem1, Jehangir Ali Shah1, Rajesh Kumar1
1National Institute of Cardiovascular Diseases, Karachi, Pakistan.
Insights
Ticagrelor was not superior to twice daily clopidogrel for reducing major adverse cardiovascular events (MACE) one month after primary percutaneous coronary intervention (PCI). However, ticagrelor significantly lowered MACE within the first two weeks post-PCI.
Area of Science:
- Cardiology
- Interventional Cardiology
- Pharmacology
Background:
- The first month after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) presents the highest risk for major adverse cardiovascular events (MACE).
- Ticagrelor and double-dose clopidogrel are established antiplatelet therapies, but direct comparative data in the STEMI post-PCI setting is limited.
Purpose of the Study:
- To evaluate the efficacy of ticagrelor compared to twice-daily clopidogrel in reducing MACE within the initial month following primary PCI for STEMI.
Main Methods:
- The TADCLOT trial was a double-blind, randomized superiority study involving 2,201 STEMI patients within 24 hours of primary PCI.
- Patients received either ticagrelor (180 mg loading, 90 mg BID) or twice-daily clopidogrel (600 mg loading, 75 mg BID) for one month.
- The primary endpoint was MACE (composite of death, myocardial infarction, stent thrombosis, stroke, or target lesion revascularization) at 30 days.
Main Results:
- No significant difference in MACE was observed between ticagrelor (2.2%) and twice-daily clopidogrel (2.9%) at 30 days (HR 0.75; P=0.28).
- Clinically significant bleeding rates were similar between the groups (0.5% ticagrelor vs. 0.4% clopidogrel).
- Ticagrelor demonstrated a significant reduction in MACE at 7 days (HR 0.15; P=0.002) and 14 days (HR 0.46; P=0.02) compared to twice-daily clopidogrel.
Conclusions:
- Ticagrelor did not prove superior to twice-daily clopidogrel in preventing MACE at one month post-primary PCI, with comparable bleeding rates.
- Despite not meeting the primary endpoint, ticagrelor showed a significant early benefit, reducing MACE within the first two weeks.
- The study suggests that while overall MACE rates were lower than anticipated, early protection may favor ticagrelor.
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).
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