Effect of remote ischaemic conditioning on platelet reactivity and endogenous fibrinolysis in ST-elevation myocardial infarction: a substudy of the CONDI-2/ERIC-PPCI randomized controlled trial

Author:

Gorog Diana A123ORCID,Farag Mohamed24,Spinthakis Nikolaos23ORCID,Yellon Derek M5,Bøtker Hans Erik6,Kharbanda Rajesh K78ORCID,Hausenloy Derek J910111213

Affiliation:

1. National Heart and Lung Institute, Faculty of Medicine, Imperial College, Dovehouse Street, London SW3 6LR, UK

2. Postgraduate Medical School, University of Hertfordshire, Hertfordshire, UK

3. Department of Cardiology, East and North Hertfordshire NHS Trust, Hertfordshire, UK

4. Cardiology Department, Royal Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, UK

5. The Hatter Cardiovascular Institute, University College London, London, UK

6. Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark

7. Cardiology Department, Oxford Heart Centre, Oxford University Hospitals NHS Trust, Oxford, UK

8. Department of Cardiovascular Medicine, University of Oxford, Oxford, UK

9. The Hatter Cardiovascular Institute,  University College London, London, UK

10. Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore

11. Department of Cardiology, National Heart Research Institute Singapore, National Heart Centre, Singapore, Singapore

12. Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore

13. Cardiovascular Research Center, College of Medical and Health Sciences, Asia University, Taichung City, Taiwan

Abstract

Abstract Aims Remote ischaemic conditioning (RIC) has been shown to reduce myocardial infarct size in animal models of myocardial infarction. Platelet thrombus formation is a critical determinant of outcome in ST-segment elevation myocardial infarction (STEMI). Whether the beneficial effects of RIC are related to thrombotic parameters is unclear. Methods and results In a substudy of the Effect of Remote Ischaemic Conditioning on clinical outcomes in STEMI patients undergoing Primary Percutaneous Coronary Intervention (ERIC-PPCI) trial, we assessed the effect of RIC on thrombotic status. Patients presenting with STEMI were randomized to immediate RIC consisting of an automated autoRIC™ cuff on the upper arm inflated to 200 mmHg for 5 min and deflated for 5 min for four cycles (n = 53) or sham (n = 47). Venous blood was tested at presentation, discharge (48 h) and 6–8 weeks, to assess platelet reactivity, coagulation, and endogenous fibrinolysis using the Global Thrombosis Test and thromboelastography. Baseline thrombotic status was similar in the two groups. At discharge, there was some evidence that the time to in vitro thrombotic occlusion under high shear stress was longer with RIC compared to sham (454 ± 105 s vs. 403 ± 105 s; mean difference 50.1 s; 95% confidence interval 93.7–6.4, P = 0.025), but this was no longer apparent at 6–8 weeks. There was no difference in clot formation or endogenous fibrinolysis between the study arms at any time point. Conclusion RIC may reduce platelet reactivity in the first 48 h post-STEMI. Further research is needed to delineate mechanisms through which RIC may reduce platelet reactivity, and whether it may improve outcomes in patients with persistent high on-treatment platelet reactivity.

Funder

British Heart Foundation Clinical Study

University College London Hospital/University College London Biomedical Research Clinical Research

Danish Innovation Foundation

Novo Nordisk Foundation

TrygFonden

British Heart Foundation

National Institute for Health Research University College London Hospitals Biomedical Research Centre

Duke-National University Singapore Medical School, Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Senior Investigator scheme

Singapore Ministry of Education Academic Research Fund Tier 2

Oxford NIHR Biomedical Centre

National Institute for Health Research

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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4. Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: trials and tribulations;Hausenloy;Eur Heart J,2017

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