• Stefan Weisshaar, Brigitte Litschauer, Tillmann Kerbel, and Michael Wolzt.
• Department of Clinical Pharmacology, Medical University of Vienna, Austria. Electronic address: stefan.weisshaar@meduniwien.ac.at.
• Int. J. Cardiol. 2018 Mar 15; 255: 1-7.

BackgroundAtorvastatin and ticagrelor have been shown to prevent against tissue injury in animals. It is unclear if these beneficial effects are also detectable in humans. We studied the effect of high-dose atorvastatin combined with ticagrelor loading on endothelial dysfunction in a model of forearm vascular ischemia-reperfusion (IR) injury.Methods32 healthy subjects (n=16 per group) were enrolled in this randomized, placebo-controlled, double-blinded trial. Forearm blood flow (FBF) measurements in response to increasing intra-arterial doses of the vasodilator acetylcholine (ACh; endothelium-dependent agonist) and glyceryltrinitrate (GTN; endothelium-independent) were performed before and after a cuff-induced 20min forearm ischemia, respectively. FBF reactivity was assessed prior to any pharmacological intervention and after 14days intake of 80mg atorvastatin once daily or placebo, followed by an oral loading dose of 180mg ticagrelor. In addition, lipoprotein parameters and platelet aggregation were evaluated.ResultsTicagrelor loading mitigated ischemia-induced endothelial dysfunction and in combination with repeated atorvastatin dosing the response to ACh during reperfusion was completely normalized (FBF AChAUC ratio post- vs. pre-ischemia: 0.81 [ticagrelor] vs. 1.04 [atorvastatin+ticagrelor]; P=0.001). As expected, GTN-induced vasodilation was not affected by IR injury. Atorvastatin significantly reduced total and low density lipoprotein cholesterol concentrations, while high density lipoprotein cholesterol and triglyceride levels remained unchanged.ConclusionChronic atorvastatin treatment combined with ticagrelor loading prevents against endothelial dysfunction after acute forearm ischemia. Ticagrelor alone mitigated the impaired endothelium-dependent FBF response as compared to no pharmacological intervention.Clinical Trial RegistrationURL: https://clinicaltrials.gov. Unique identifier: NCT02910778.Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

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