ORIGINAL ARTICLE
Remote ischemic preconditioning inhibits platelet αIIbβ3 activation in coronary artery disease patients receiving dual antiplatelet therapy: A randomized trial

https://doi.org/10.1111/jth.14763Get rights and content
Under an Elsevier user license
open archive

Abstract

Objectives

We investigated whether remote ischemic preconditioning (RIPC) inhibits agonist‐induced conformational activation of platelet αIIbβ3 in patients with coronary artery disease already receiving conventional antiplatelet therapy.

Patients/Methods

Consecutive patients with angiographically confirmed coronary artery disease were randomized to RIPC or sham treatment. Venous blood was collected before and immediately after RIPC/sham. Platelet aggregometry (ADP, arachidonic acid) and whole blood platelet flow cytometry was performed for CD62P, CD63, active αIIbβ3 (PAC‐1 binding) before and after stimulation with ADP, thrombin ± collagen, or PAR‐1 thrombin receptor agonist.

Results

Patients (25 RIPC, 23 sham) were well matched, 83% male, age (mean ± standard deviation) 63.3 ± 13.2 years, 95% aspirin, 81% P2Y12 inhibitor. RIPC did not affect platelet aggregation, nor agonist‐induced expression of CD62P, but selectively and significantly decreased αIIbβ3 activation after stimulation with either PAR‐1 agonist peptide or the combination of thrombin + collagen, but not after ADP nor thrombin alone. The effect of RIPC on platelet αIIbβ3 activation was evident in patients receiving both aspirin and P2Y12 inhibitor, and was not associated with an increase in vasodilator‐stimulated phosphoprotein phosphorylation.

Conclusions

Remote ischemic preconditioning inhibits conformational activation of platelet αIIbβ3 in response to exposure to thrombin and collagen in patients with coronary artery disease receiving dual antiplatelet therapy. These findings indicate agonist‐specific inhibition of platelet activation by RIPC in coronary artery disease that is not obviated by the prior use of P2Y12 inhibitors.

Keywords

coronary artery disease
ischemic preconditioning
platelet activation
platelet antagonists
platelet glycoprotein GPIIb‐IIIa complex

Cited by (0)

Leonard Kritharides and Vivien M. Chen contributed equally to this work.

This work was carried out at Concord Hospital and the ANZAC Research Institute, Sydney, Australia.

This study is registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12616000486426, www.anzctr.org.au).

Manuscript handled by: Yukio Ozaki

Final decision: Yukio Ozaki, 6 February 2020

Funding informationJKL was supported by an NHMRC/National Heart Foundation of Australia Postgraduate Scholarship (1094384). Equipment maintenance was supported by a Sydney Local Heath District Infrastructure Grant. Sponsors had no role in the study design, data analysis, data interpretation, or writing of the manuscript. There was no additional external funding received for this study.