Ticagrelor mitigates ischaemia–reperfusion induced vascular endothelial dysfunction in healthy young males – a randomized, single-blinded study

Abstract

Aims: Animal data suggest that ticagrelor but not clopidogrel protects against tissue injury. It is unclear if this effect of ticagrelor is also detectable in humans. We studied the effect of ticagrelor and clopidogrel at standard clinical doses on endothelial dysfunction in an experimental model of forearm vascular ischaemia–reperfusion (IR) injury. Methods: In a randomized, single-blinded trial, 24 subjects underwent forearm blood flow (FBF) measurements in response to the endothelium-dependent vasodilator acetylcholine (ACh) and to glyceryltrinitrate (GTN; endothelium-independent) before and after a 20 min forearm ischaemia. FBF reactivity was assessed after an oral loading dose of ticagrelor or clopidogrel and after 14 days of regular intake of maintenance doses of the study medicines. In addition, the effect on platelet inhibition was evaluated using multiple electrode aggregometry. Results: ACh-induced vasodilation was impaired during reperfusion and not completely normalized by acute or chronic treatment with ticagrelor or clopidogrel (post- vs. pre-ischaemia). However, ticagrelor mitigated endothelial dysfunction compared to clopidogrel after loading (FBF AChAUC ratio post- vs. pre-ischaemia: 0.83 [0.70; 0.96] vs. 0.64 [0.56; 0.72]; P = 0.024) and after chronic administration (FBF AChAUC ratio: 0.86 [0.71; 1.00] vs. 0.66 [0.55; 0.77]; P = 0.027). As expected, GTN-induced vasodilation was not affected by ischaemia. Ticagrelor or clopidogrel treatment inhibited platelet activation to a similar degree. Conclusion: Our data indicate that ticagrelor treatment exerts a greater vascular salutary effect than clopidogrel during reperfusion after an acute vascular occlusion. IR-induced vascular injury cannot be prevented completely by administration of these antiplatelet agents at standard clinical doses.