Effects of ischaemic conditioning on major clinical outcomes in people undergoing invasive procedures: systematic review and meta-analysis.
OBJECTIVE
To summarise the benefits and harms of ischaemic conditioning on major clinical outcomes in various settings.


METHODS
Systematic review and meta-analysis.


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


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


METHODS
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.
The George Institute for Global Health, University of Sydney, Sydney, NSW 2050, Australia.|Concord Clinical School, University of Sydney, Sydney, Australia.
Louisa
L
Sukkar
The George Institute for Global Health, University of Sydney, Sydney, NSW 2050, Australia.|Division of Nephrology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
Daqing
D
Hong
The George Institute for Global Health, University of Sydney, Sydney, NSW 2050, Australia.
Muh Geot
MG
Wong
The George Institute for Global Health, University of Sydney, Sydney, NSW 2050, Australia.|St George Hospital, Kogarah, NSW, Australia.
Sunil V
SV
Badve
The George Institute for Global Health, University of Sydney, Sydney, NSW 2050, Australia.
Kris
K
Rogers
The George Institute for Global Health, University of Sydney, Sydney, NSW 2050, Australia.
Vlado
V
Perkovic
Departments of Medicine, Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.|Population Health Research Institute, Hamilton, ON, Canada.
Michael
M
Walsh
Sun Yat-Sen University, Guangdong Province, China.
Xueqing
X
Yu
The George Institute for Global Health, University of Sydney, Sydney, NSW 2050, Australia.|University of Western Australia, Crawley, WA, Australia.
Graham S
GS
Hillis
The George Institute for Global Health, University of Sydney, Sydney, NSW 2050, Australia.|Concord Clinical School, University of Sydney, Sydney, Australia.
Martin
M
Gallagher
The George Institute for Global Health, University of Sydney, Sydney, NSW 2050, Australia.|Concord Repatriation General Hospital, Sydney, Australia.
Meg
M
Jardine
D058186:Acute Kidney Injury / Q000517:prevention & control; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D051799:Delayed Graft Function / Q000517:prevention & control; D006801:Humans; D019194:Ischemic Preconditioning; D009203:Myocardial Infarction / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000517:prevention & control; D013514:Surgical Procedures, Operative / Q000401:mortality