Effects of ticagrelor monotherapy vs. clopidogrel monotherapy on platelet reactivity: a randomized, crossover clinical study (SINGLE study)

Abstract

Increasing clinical trials demonstrated that the discontinuation of aspirin while maintaining a P2Y₁₂ inhibitor monotherapy could decrease the risk of bleeding without losing the antithrombotic effect. However, no data are available on the platelet reactivity of patients undergoing ticagrelor monotherapy vs. clopidogrel. Therefore, we performed this study to observe the efficacy of ticagrelor monotherapy vs. clopidogrel in Chinese patients with chronic coronary syndrome. This randomized, single-blinded, crossover trial enrolled 50 patients who were administered with ticagrelor (90 mg twice daily for 2 weeks) or clopidogrel (75 mg once daily for 2 weeks). Followed by a 2-week washout period, the two groups of patients underwent a crossover trial. Light transmission aggregometry (LTA) and thromboelastography (TEG) assays were used to test platelet reactivity. The platelet aggregation rate (PAgR) of ADP and AA was significantly lower with ticagrelor than clopidogrel (PAgR of ADP, 27.30% (7.30%-42.635%) vs. 35.55% (12.03%-69.25%), P = .0254; PAgR of AA, 77.80% (21.60%-86.43%) vs. 83.10% (67.13%-87.20%), P = .0400). There was no significant difference in PAgR of collagen and epinephrine between the two groups. The TEG assay showed that ADP and AA, which induced the inhibition of platelet aggregation, were significantly higher in the ticagrelor group than those in the clopidogrel group [ADP%, 69.00% (59.68%–88.95%) vs. 60.55% (35.98%–78.35%), P = .0020; AA%, 53.65% (22.75%–79.28%) vs. 15.15% (5.75%–70.25%), P = .0127]. High on-treatment platelet reactivity (HTPR) on ADP was 2.17% with ticagrelor and 19.57% with clopidogrel. HTPR on AA was 50.00% with ticagrelor and 69.57% with clopidogrel. Ticagrelor and clopidogrel caused the inhibition of ADP and AA-induced platelet aggregation. Moreover, ticagrelor monotherapy had a stronger inhibitory effect than clopidogrel monotherapy (except on collagen and epinephrine).

Keywords:

• Chronic coronary syndrome
• clopidogrel
• platelet aggregation
• ticagrelor

Acknowledgements

We are grateful to Junsheng Jing for his excellent technical support.

Contributorship Statement

Yue Li and Meijiao He were responsible for the concept and design of the study. Meijiao He was responsible for the study coordination and conduct. Yue Li, Jing Shi, Meijiao He and Wei Yan contributed to the drafting of the manuscript. Yun Zhang, Yihui Kong, Xuejie Han, Jie Ren and Zhongyang Zhao collected and analysed the data. Guangzhong Liu interpreted the data.

Disclosure Statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the grants from National Natural Science Foundation of China (No. 81830012), Youth Program of the National Natural Science Foundation of China (No. 81900374), and CS Optimizing Antithrombotic Research Fund (BJUHFCSOARF201801- 09).