Comparison of the Effects of Ticagrelor and Clopidogrel on Microvascular Dysfunction in Patients With Acute Coronary Syndrome Using Invasive Physiologic Indices

Abstract

Background: Ticagrelor reduced the rate of myocardial infarction and death compared with clopidogrel in patients with acute coronary syndrome. However, little is understood about chronic treatment of ticagrelor on microvascular dysfunction. The objective of this study was to assess the impact of ticagrelor maintenance treatment on microvascular system and coronary flow in comparison with clopidogrel. Methods: This study was a nonblinded, open-label, parallel-group, prospective, randomized controlled trial that enrolled 120 patients with acute coronary syndrome requiring stent implantation. Patients were randomized into the ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 to 600 mg loading dose, 75 mg daily thereafter) group. The primary end point was coronary microvascular dysfunction as measured by an index of microcirculatory resistance (IMR) at 6 months after treatment. Results: The baseline clinical characteristics and physiological parameters, such as fractional flow reserve, coronary flow reserve, and IMR, did not differ between the ticagrelor and clopidogrel groups. Six-month follow-up physiological data showed that the IMR value was significantly lower in the ticagrelor group than the clopidogrel group (15.57±5.65 versus 21.15±8.39, P <0.01), and coronary flow reserve was higher in the ticagrelor group than in the clopidogrel group (3.85±0.72 versus 3.37±0.76, P <0.01). However, there was no difference in fractional flow reserve (0.87±0.08 versus 0.87±0.09, P =0.94) between the 2 groups. The improvement in IMR after 6 months of treatment was higher in the ticagrelor group ( P <0.01). Analyses of 223 nonculprit vessels of registered patients based on physiological results showed no differences in baseline fractional flow reserve (0.93±0.13 versus 0.92±0.09, P =0.58), coronary flow reserve (3.62±1.27 versus 3.51±1.24, P =0.16), or IMR (21.37±12.37 versus 24.19±21.08, P =0.22) or in follow-up fractional flow reserve (0.91±0.09 versus 0.91±0.08, P =0.67), coronary flow reserve (3.91±1.22 versus 3.75±1.16, P =0.36), or IMR (19.43±10.32 versus 21.52±18.90, P =0.34) between the 2 groups. Conclusions: Compared with clopidogrel, 6 months of ticagrelor therapy significantly improved microvascular dysfunction in acute coronary syndrome patients with stent implantation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02618733.