Elsevier

The Lancet

Volume 375, Issue 9716, 27 February–5 March 2010, Pages 727-734
The Lancet

Articles
Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial

https://doi.org/10.1016/S0140-6736(09)62001-8Get rights and content

Summary

Background

Remote ischaemic preconditioning attenuates cardiac injury at elective surgery and angioplasty. We tested the hypothesis that remote ischaemic conditioning during evolving ST-elevation myocardial infarction, and done before primary percutaneous coronary intervention, increases myocardial salvage.

Methods

333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerised block randomisation to receive primary percutaneous coronary intervention with (n=166 patients) versus without (n=167) remote conditioning (intermittent arm ischaemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to hospital, and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00435266.

Findings

82 patients were excluded on arrival at hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0·75 (IQR 0·50–0·93, n=73) in the remote conditioning group versus 0·55 (0·35–0·88, n=69) in the control group, with median difference of 0·10 (95% CI 0·01–0·22; p=0·0333); mean salvage index was 0·69 (SD 0·27) versus 0·57 (0·26), with mean difference of 0·12 (95% CI 0·01–0·21; p=0·0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group), and heart failure (n=3 per group).

Interpretation

Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. Our findings merit a larger trial to establish the effect of remote conditioning on clinical outcomes.

Funding

Fondation Leducq.

Introduction

ST-elevation myocardial infarction is a leading cause of mortality and morbidity. Infarct size is an important determinant of outcome. Hence reduction of myocardial injury is a therapeutic mainstay, best achieved by early reperfusion through primary percutaneous coronary intervention.1 Patients receiving such treatment will achieve infarct-related vessel patency and reperfusion, but risk sustaining clinically significant myocardial infarction, even when the procedure is done soon after symptom onset.2 Attempts to improve outcomes with adjuvant mechanical treatments such as thrombectomy and distal protection devices show inconsistent benefit.3, 4, 5

An alternative approach for treatment is to exploit innate cytoprotective mechanisms. Findings from recent studies of local postconditioning and targeting of mitochondrial pathways in myocardial infarction have indicated success in reduction of infarct size in patients with occluded left anterior descendent artery.6, 7 Remote ischaemic preconditioning, induced by repeated brief periods of limb ischaemia before index ischaemia,8 reduces myocardial injury in patients exposed to predictable ischaemia.9, 10, 11 Furthermore, remote ischaemic postconditioning, applied in the early reperfusion phase after prolonged ischaemia, seems to be more effective than local postconditioning in experimental myocardial infarction.12 We have shown that conditioning, by intermittent limb ischaemia after the onset of myocardial ischaemia and before reperfusion, reduces infarct size in a porcine model.13 This simple technique can be used during hospital transport.

We used myocardial perfusion imaging to examine whether remote ischaemic conditioning done before primary percutaneous coronary intervention increases myocardial salvage, a predictor of mortality,14 in patients with a first acute and evolving myocardial infarction.

Section snippets

Patients

This prospective, single-centre randomised controlled trial was done during February, 2007–November, 2008 in Aarhus University Hospital Skejby, Aarhus N, Denmark. Eligible patients were aged 18 years or older; presented with chest pain before admission to hospital and within 12 h of onset; had ST-segment elevation of more than 0·1 mV in two contiguous leads in the first electrocardiogram (ECG) recorded on the scene; and were telemedically assigned the clinical decision to receive primary

Results

Figure 1 shows the trial profile. 333 patients were assessed during ambulance transport and randomly allocated to treatment, but 82 patients did not fulfil entry criteria on arrival at the hospital and were excluded. Of the remaining 251 patients, final infarct size was obtained in 110 (88%) patients in the control group and 109 (87%) in the intervention group. A lack of 24-h imaging availability meant that acute myocardial perfusion imaging was not possible in all patients within 8 h after

Discussion

Our study shows that remote ischaemic conditioning, induced by intermittent upper-arm ischaemia and done before primary percutaneous coronary intervention, can attenuate reperfusion injury in patients with evolving myocardial infarction, thereby resulting in increased myocardial salvage. This protective effect seemed to be strongest in patients with totally occluded vessels and with infarcts in the left anterior descending artery—both of which were associated with almost double the area at

References (28)

  • T Svilaas et al.

    Thrombus aspiration during primary percutaneous coronary intervention

    N Engl J Med

    (2008)
  • P Staat et al.

    Postconditioning the human heart

    Circulation

    (2005)
  • C Piot et al.

    Effect of cyclosporine on reperfusion injury in acute myocardial infarction

    N Engl J Med

    (2008)
  • RK Kharbanda et al.

    Transient limb ischemia induces remote ischemic preconditioning in vivo

    Circulation

    (2002)
  • Cited by (855)

    View all citing articles on Scopus
    View full text