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N Engl J Med. 2015 Oct 8;373(15):1408-17. doi: 10.1056/NEJMoa1413534. Epub 2015 Oct 5.

Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery.

Collaborators (392)

Goss A, Desouza A, Relvas C, Morgan H, Saunders I, Donovan J, Booth J, Shah M, Yates M, Chawla N, Stanger O, Savory R, Trimlett R, Gonella R, Wang S, Morgan T, Roesler V, Suri A, Jarvis C, Warren L, Xenou M, Tehrani S, Sivaraman V, Roberts N, Lawrence D, Di Salvo C, Barnard M, Martin B, Smith A, Malik A, Cortez A, O'Donovan M, Shand N, Desai J, Eka A, Williams A, Kunst G, Jessup J, Breeze J, Salaunkey K, Andrews M, Joseph M, Williams R, Bristol R, Patale S, Preston T, Dew T, Hogervorst V, Jenkins D, Kenny A, Freeman C, Kelly C, Salisbury D, King E, Marston K, Fingleton L, Myszko L, Bennett M, Lowry R, Woods S, Fakelman S, Deeley S, Dean T, Howlett T, Hacking A, Pooley M, Sudarshan C, Ng C, Nashef S, Catarino P, Codispoti M, Large S, Dunning J, Nair S, Abuomar Y, Punjabi P, Macys A, Pengelley C, Moscarelli M, Munro I, Scriven J, Smee J, Iddamalgoda T, Chan K, Salam AA, Jahangiri M, Edwards B, Cousins E, Nyamajiyah H, Clutterbuck L, Smith M, Rajab M, Day S, Blauth C, Damm J, Wilson K, Clack L, Straiton N, Jones S, Clark S, Russell V, Taylor Y, Uppal R, Barrett C, Habada H, Veerapen J, Lungley J, Baig K, Martin C, Andiapen M, Dowlut S, Brookman P, Prossora M, Ritchie A, Birdi I, Pilcher A, Solesbury A, Sevillano A, Hadebe B, Alves C, Alves D, Hamarneh A, Redman E, Butt G, Chitty H, Udeozor I, Hampton-Till J, Byrne J, Guinto J, Tidey J, Hayden K, Goodsell K, Cruse L, Bondoc M, Masuku M, Christmas N, Mguni N, Harding P, Koothoor R, Adeniba R, Theodule R, Tshumi S, Pepper S, Moyo S, McCormick C, Allen K, Trivedi U, MacKenzie A, Cohen A, McGregor A, Hill A, Cowling C, Joyce E, Peasgood E, Roberts E, Wickham E, Duncan F, Duncliffe J, Hyde J, Roberts L, Bennett L, Cooper L, Maccario M, Millar M, Lewis M, Hutchinson N, Skipper N, Cooter N, Kong R, Berg G, Aitken C, Boyd E, Kelly J, Mason M, Small R, Simon A, Hughes C, Gowen M, Dolphin N, Warsama S, Pessotto R, Fairbairn A, Ferrara A, Marshall L, Laird M, Van Dalen M, Morrissey M, De Haan M, Giordano V, Bhabra M, Luckraz H, Smallwood A, Greatbatch E, Jarvis E, Dean-Goodridge F, Phiri L, Kempson S, Metherell S, Angelini G, Treagus A, Gravani A, Hopkins E, Wilcox J, Evans J, Rajakaruna K, Painter K, Wright K, Culliford L, Wahab M, Lambert P, Wyatt R, Underwood W, Keenan D, Paschalis A, Tallon B, Cummings-Fosong G, Phillips H, Iles-Smith H, Palmer K, Maciver K, Doyle L, O'Keeffe N, Evans S, McLoughlin S, Williams S, Kanyama S, Elwood S, Osborne W, Youhana A, Davies AS, Jones C, Fagan C, Griffiths J, Scott J, Blytt-Jordens N, Thomas R, Morgan R, Mehta D, Waters A, Marco AL, John A, Luen A, Braim D, Rathod J, Podila SR, Rajnish R, James S, Roberts T, Unsworth-White J, Stewart C, Brown C, Lloyd C, Waugh D, Alderton J, Tantam K, Barrett L, Pearse M, Persad N, Brockman P, Wosley R, Olver S, Riches T, Colwell W, Briffa N, Alli A, Jenkins A, Weedon A, Bailey C, King C, Okhuoya F, Mackenzie F, Mills G, Lindley J, Humphreys J, Fofie J, Sorrell J, Hill L, Agyemang M, Deighton M, Braidley P, Walker R, Warren R, Kerrison S, Jackson Y, Richens D, Szafranek A, Mahmoud A, Singh A, Skinner H, Skoyles J, Shajar M, Ther G, Muthuswammy G, Richards J, Dakkak K, Wyllie L, Sadhahalli P, Basu R, Jutley R, Bose A, Mitchell B, Brennan E, Hatton G, Angus K, Flannery L, Ullyott L, Helliwell L, Lane L, Puronit M, Caswell M, Pickervance S, Waterhouse C, Vasudevan V, Srivastava V, Yonan N, Moran A, Oommen A, Leonard D, Daniel D, Flook E, Hashmi F, Perks H, Kirwan M, Ferguson S, Mcnamara T, Spyt T, Alexander D, Szostek J, Maxfield K, Hickey M, Williams M, Worthy S, Legi S, Ohri S, Diprose P, Curry A, Wilkinson K, King A, Jarca A, Wadams B, Tyrell B, Bolger C, Grinyer E, Ekins E, Beckett G, Collins H, Crockett J, Piper J, Salmon K, Golder K, Seaward L, Gill R, Deng W, Bannister W, Tantony N, O'Regan D, Wilby E, Birch S, Elliot S, Beardow Z, Goodwin A, Atkinson B, Richardson C, Morley E, Robinson H, Brown I, Thompson L, Finlayson M, Hill P, Simmons S, Cormack S, Abid Q, Sellars E, Delaney J, Machin J, Barnett L, Castro-Foskett K, Griffiths M, Gallagher S, Wain J, Martin M, Bhudia S, Gibson C, Gocher D, Archer E, Ward G, Ting J, Lindsay J, McCauley M, Hawthorne N, Gibbons-Smith S, Clay S.

Author information

From the Hatter Cardiovascular Institute, University College London (D.J.H., L.C., M.X., D.M.Y.), the National Institute of Health Research University College London Hospitals Biomedical Research Centre (D.J.H., D.M.Y.), the Clinical Trials Unit, London School of Hygiene and Tropical Medicine (R.E., R.K., J.N., S.R., T.C.), the Nuffield Trust (C.A.), the Heart Hospital, University College London Hospital (S.K.); King's College London and King's College Hospital (G.K.); Royal Free Hospital (C.L.); and the National Institute of Health Research Cardiovascular Biomedical Research Unit at Royal Brompton and Harefield NHS Trust (J.P.), London, and Papworth Hospital, Cambridge (D.P.J.) - all in the United Kingdom; and the National Heart Research Institute Singapore, National Heart Centre Singapore (D.J.H.), and the Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (D.J.H.) - both in Singapore.



Whether remote ischemic preconditioning (transient ischemia and reperfusion of the arm) can improve clinical outcomes in patients undergoing coronary-artery bypass graft (CABG) surgery is not known. We investigated this question in a randomized trial.


We conducted a multicenter, sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG (with or without valve surgery) with blood cardioplegia. After anesthesia induction and before surgical incision, patients were randomly assigned to remote ischemic preconditioning (four 5-minute inflations and deflations of a standard blood-pressure cuff on the upper arm) or sham conditioning (control group). Anesthetic management and perioperative care were not standardized. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization, or stroke, assessed 12 months after randomization.


We enrolled a total of 1612 patients (811 in the control group and 801 in the ischemic-preconditioning group) at 30 cardiac surgery centers in the United Kingdom. There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group (212 patients [26.5%] and 225 patients [27.7%], respectively; hazard ratio with ischemic preconditioning, 0.95; 95% confidence interval, 0.79 to 1.15; P=0.58). Furthermore, there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury (assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours), inotrope score (calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery), acute kidney injury, duration of stay in the intensive care unit and hospital, distance on the 6-minute walk test, and quality of life.


Remote ischemic preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery. (Funded by the Efficacy and Mechanism Evaluation Program [a Medical Research Council and National Institute of Health Research partnership] and the British Heart Foundation; ERICCA number, NCT01247545.).

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