Effect of Ticagrelor Versus Clopidogrel on Aortic Stiffness in Patients With Coronary Artery Disease

Charalambos Vlachopoulos, Christos Georgakopoulos, Panagiota Pietri, Nikolaos Ioakeimidis, Michael Koutouzis, Sophia Vaina, Konstantinos Aznaouridis, Konstantinos Toutouzas, George Latsios, Dimitrios Terentes-Printzios, Aggeliki Rigatou, Dimitris Tousoulis, Charalambos Vlachopoulos, Christos Georgakopoulos, Panagiota Pietri, Nikolaos Ioakeimidis, Michael Koutouzis, Sophia Vaina, Konstantinos Aznaouridis, Konstantinos Toutouzas, George Latsios, Dimitrios Terentes-Printzios, Aggeliki Rigatou, Dimitris Tousoulis

Abstract

Background We compared the acute and midterm effect of ticagrelor versus clopidogrel on aortic stiffness. Methods and Results We studied 117 patients in a randomized, assessor-blinded, parallel-group trial. The acute effect of ticagrelor was studied in 58 patients randomized (1:1) to receive a loading dose of clopidogrel (600 mg) or ticagrelor (180 mg). Carotid-femoral pulse wave velocity (cf PWV ) was measured before, 3, and 24 hours after the loading dose. The midterm effect (30-day treatment period) was studied in 59 subjects who underwent percutaneous coronary intervention and were randomized to either clopidogrel (75 mg, OD) or ticagrelor (90 mg BID). cf PWV was measured before and at 30 days of treatment. Circulating markers of inflammation and endothelial function were measured at all study points. Repeated-measures analysis showed a significant main effect for treatment ( P=0.03), with the ticagrelor showing a reduction in cf PWV after treatment. cf PWV at 24 hours was significantly lower in the ticagrelor group compared with the clopidogrel group ( P=0.017) (maximal response reduction by 0.42±0.26 m/s). At 30 days, cf PWV decreased in the ticagrelor group, whereas there was no change with clopidogrel (-0.43±0.57 versus 0.12±0.14 m/s, P=0.004). There were no significant changes in both the acute and midterm study period in the pro-inflammatory and endothelial function parameters. Conclusions URL : https://www.clinicaltrials.gov . Unique identifier: NCT02071212. Ticagrelor decreases cf PWV for 24 hours after the loading dose and at 1 month post-percutaneous coronary intervention compared with clopidogrel. Considering that aortic stiffness is an independent predictor of cardiovascular events, this finding may have clinical implications regarding the beneficial effect of ticagrelor. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT02071212.

Keywords: adenosine; aortic stiffness; clopidogrel; coronary artery disease; ticagrelor.

Figures

Figure 1
Figure 1
Participant recruitment flow chart of the acute and midterm studies.
Figure 2
Figure 2
cfPWV according to antiplatelet loading dose (ticagrelor vs clopidogrel) measured across time points during the overall study time course. ANCOVA P value indicates the main effect (between‐subjects effect) for treatment. cfPWV expressed as means; errors bars indicate SE. *P<0.05 in post hoc comparisons between ticagrelor and clopidogrel at 24 hours. cfPWV indicates carotid‐femoral pulse wave velocity.
Figure 3
Figure 3
Comparison of changes in cfPWV at 30‐day follow‐up after ticagrelor and clopidogrel daily administration. P values at the top of graph by ANCOVA. Error bars indicate SE. *P<0.001 compared with baseline value (paired t test). cfPWV indicates carotid‐femoral pulse wave velocity.

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