Dataset Information

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.

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.

SUBMITTER: Gorog DA

PROVIDER: S-EPMC7820881 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRemote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months.MethodsWe did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed.FindingsBetween Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

Project description:BackgroundWe aimed to evaluate the effect of early intravenous metoprolol treatment, microvascular obstruction (MVO), intramyocardial hemorrhage (IMH) and adverse left ventricular (LV) remodeling on the evolution of infarct and remote zone circumferential strain after acute anterior ST-segment elevation myocardial infarction (STEMI) with feature-tracking cardiovascular magnetic resonance (CMR).MethodsA total of 191 patients with acute anterior STEMI enrolled in the METOCARD-CNIC randomized clinical trial were evaluated. LV infarct zone and remote zone circumferential strain were measured with feature-tracking CMR at 1 week and 6 months after STEMI.ResultsIn the overall population, the infarct zone circumferential strain significantly improved from 1 week to 6 months after STEMI (- 8.6 ± 9.0% to - 14.5 ± 8.0%; P < 0.001), while no changes in the remote zone strain were observed (- 19.5 ± 5.9% to - 19.2 ± 3.9%; P = 0.466). Patients who received early intravenous metoprolol had significantly more preserved infarct zone circumferential strain compared to the controls at 1 week (P = 0.038) and at 6 months (P = 0.033) after STEMI, while no differences in remote zone strain were observed. The infarct zone circumferential strain was significantly impaired in patients with MVO and IMH compared to those without (P < 0.001 at 1 week and 6 months), however it improved between both time points regardless of the presence of MVO or IMH (P < 0.001). In patients who developed adverse LV remodeling (defined as ≥ 20% increase in LV end-diastolic volume) remote zone circumferential strain worsened between 1 week and 6 months after STEMI (P = 0.036), while in the absence of adverse LV remodeling no significant changes in remote zone strain were observed.ConclusionsRegional LV circumferential strain with feature-tracking CMR allowed comprehensive evaluation of the sequelae of an acute STEMI treated with primary percutaneous coronary intervention and demonstrated long-lasting cardioprotective effects of early intravenous metoprolol.Trial registrationClinicalTrials.gov, NCT01311700. Registered 8 March 2011 - Retrospectively registered.

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