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Comparing the effect of clopidogrel versus ticagrelor on coronary microvascular dysfunction in acute coronary syndrome patients (TIME trial): study protocol for a randomized controlled trial

Sang-Don Park, Yong-Soo Baek, Seong-Ill Woo, Soo-Han Kim, Sung-Hee Shin, Dae-Hyeok Kim*, Jun Kwan and Keum-Soo Park

Author Affiliations

Department of Internal Medicine, Inha University Hospital, 7-206, 3-GA Sinheung-Dong, Jung-gu, Incheon 400-711, South Korea

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Trials 2014, 15:151  doi:10.1186/1745-6215-15-151

Published: 1 May 2014



Although prompt reperfusion treatment restores normal epicardial flow, microvascular dysfunction may persist in some patients with acute coronary syndrome (ACS). Impaired myocardial perfusion is caused by intraluminal platelets, fibrin thrombi and neutrophil plugging; antiplatelet agents play a significant role in terms of protecting against thrombus microembolization. A novel antiplatelet agent, ticagrelor, is a non-thienopyridine, direct P2Y12 blocker that has shown greater, more rapid and more consistent platelet inhibition than clopidogrel. However, the effects of ticagrelor on the prevention of microvascular dysfunction are uncertain. The present study is a comparison between clopidogrel and ticagrelor use for preventing microvascular dysfunction in patients with ST elevation or non-ST elevation myocardial infarction (STEMI or NSTEMI, respectively).


The TIME trial is a single-center, randomized, open-label, parallel-arm study designed to demonstrate the superiority of ticagrelor over clopidogrel. A total of 152 patients with a spectrum of STEMI or NSTEMI will undergo prospective random assignment to clopidogrel or ticagrelor (1:1 ratio). The primary endpoint is an index of microcirculatory resistance (IMR) measured after percutaneous coronary intervention (PCI); the secondary endpoint is wall motion score index assessed at 3 months by using echocardiography.


The TIME trial is the first study designed to compare the protective effect of clopidogrel and ticagrelor on coronary microvascular dysfunction in patients with STEMI and NSTEMI.

Trial registration NCT02026219. Registration date: 24 December 2013.

MeSH terms; Myocardial infarction; Antiplatelet agents; Microcirculation