Gorog, DA; Farag, M; Spinthakis, N; Yellon, DM; Bøtker, HE; Kharbanda, RK; Hausenloy, DJ; (2020) Effect of remote ischaemic conditioning on platelet reactivity and endogenous fibrinolysis in ST-elevation myocardial infarction- a substudy of the CONDI-2/ERIC-PPCI randomised controlled trial. Cardiovascular Research 10.1093/cvr/cvaa061. (In press).

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Abstract

Background: 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 randomised to immediate RIC consisting of an automated autoRICTM cuff on the upper arm inflated to 200mmHg for 5 minutes and deflated for 5 minutes for 4 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 (TEG). Baseline thrombotic status was similar in the 2 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±105s vs. 403±105s; mean difference 50.1s; 95% confidence interval [CI] 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 48h 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. / Translational Perspective: ST-elevation myocardial infarction (STEMI) results from coronary thrombosis. Remote ischaemic conditioning (RIC) can reduce infarct size in animals, but its effects on thrombus formation are unclear. We show that in patients with STEMI, the time to in vitro thrombotic occlusion was longer in patients receiving RIC than sham at 48h, but this was no longer apparent at 6-8 weeks. There was no difference in coagulation or endogenous fibrinolysis between RIC and sham groups. The short-term reduction in platelet reactivity by RIC may be useful in individuals with enhanced platelet reactivity to reduce the propensity for further thrombosis.

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