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Effects of ischaemic conditioning on major clinical outcomes in people undergoing invasive procedures: systematic review and meta-analysis

BMJ 2016; 355 doi: https://doi.org/10.1136/bmj.i5599 (Published 07 November 2016) Cite this as: BMJ 2016;355:i5599
  1. Louisa Sukkar, research fellow1 2,
  2. Daqing Hong, visiting fellow1 3,
  3. Muh Geot Wong, senior research fellow1,
  4. Sunil V Badve, research fellow1 4,
  5. Kris Rogers, statistician1,
  6. Vlado Perkovic, professor of medicine1,
  7. Michael Walsh, assistant professor5 6,
  8. Xueqing Yu, professor of medicine7,
  9. Graham S Hillis, professor of medicine1 8,
  10. Martin Gallagher, associate professor of medicine1 2,
  11. Meg Jardine, associate professor of medicine1 9
  1. 1The George Institute for Global Health, University of Sydney, Sydney, NSW 2050, Australia
  2. 2Concord Clinical School, University of Sydney, Sydney, Australia
  3. 3Division of Nephrology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, China
  4. 4St George Hospital, Kogarah, NSW, Australia
  5. 5Departments of Medicine, Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada
  6. 6Population Health Research Institute, Hamilton, ON, Canada
  7. 7Sun Yat-Sen University, Guangdong Province, China
  8. 8University of Western Australia, Crawley, WA, Australia
  9. 9Concord Repatriation General Hospital, Sydney, Australia
  1. Correspondence to: M Gallagher mgallagher{at}georgeinstitute.org.au
  • Accepted 4 October 2016

Abstract

Objective To summarise the benefits and harms of ischaemic conditioning on major clinical outcomes in various settings.

Design Systematic review and meta-analysis.

Data sources Medline, Embase, Cochrane databases, and International Clinical Trials Registry platform from inception through October 2015.

Study selection All randomised controlled comparisons of the effect of ischaemic conditioning on clinical outcomes were included.

Data extraction Two authors independently extracted data from individual reports. Reports of multiple intervention arms were treated as separate trials. Random effects models were used to calculate summary estimates for all cause mortality and other pre-specified clinical outcomes. All cause mortality and secondary outcomes with P<0.1 were examined for study quality by using the GRADE assessment tool, the effect of pre-specified characteristics by using meta-regression and Cochran C test, and trial sequential analysis by using the Copenhagen Trial Unit method.

Results 85 reports of 89 randomised comparisons were identified, with a median 80 (interquartile range 60-149) participants and median 1 (range 1 day-72 months) month intended duration. Ischaemic conditioning had no effect on all cause mortality (68 comparisons; 424 events; 11 619 participants; risk ratio 0.96, 95% confidence interval 0.80 to 1.16; P=0.68; moderate quality evidence) regardless of the clinical setting in which it was used or the particular intervention related characteristics. Ischaemic conditioning may reduce the rates of some secondary outcomes including stroke (18 trials; 5995 participants; 149 events; risk ratio 0.72, 0.52 to 1.00; P=0.048; very low quality evidence) and acute kidney injury (36 trials; 8493 participants; 1443 events; risk ratio 0.83, 0.71 to 0.97; P=0.02; low quality evidence), although the benefits seem to be confined to non-surgical settings and to mild episodes of acute kidney injury only.

Conclusions Ischaemic conditioning has no overall effect on the risk of death. Possible effects on stroke and acute kidney injury are uncertain given methodological concerns and low event rates. Adoption of ischaemic conditioning cannot be recommended for routine use unless further high quality and well powered evidence shows benefit.

Footnotes

  • Contributors: VP, MG and MJ were responsible for the study concept. LS, SVB, MW, MG, and MJ were responsible for study design. SVB was responsible for the literature search. LS and MGH were responsible for study selection. LS and DH were responsible for data extraction. MJ and KR were responsible for statistical analysis. LS, DH, MGW, SVB, KR, MW, VP, XY, GSH, MG, and MJ were responsible for data analysis and interpretation. MG, MJ, and LS were responsible for drafting the manuscript. LS, DH, MGW, SVB, KR, VP, XY, GSH, MG, and MJ were responsible for critical revision of the manuscript. MG is the guarantor.

  • Funding: There was no specific funding source for this study. LS was supported by an Australian postgraduate award and a George Institute for Global Health postgraduate scholarship. DH is supported by a Youth Science and Technology Creative Research Groups of Sichuan Province scholarship. VP is supported by a senior research fellowship from the National Health and Medical Research Council of Australia. MGW was supported by a new investigator award from the Canadian Institutes of Health Research. MJ was supported by a career development fellowship from the National Health and Medical Research Council of Australia and by the National Heart Foundation.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work other than that described above; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work [or describe if any]..

  • Ethical approval: Not needed.

  • Data sharing: No additional data available.

  • Transparency: The lead author (the manuscript’s guarantor) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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