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@NEJM Ask the Authors & Experts: A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery

Original Article

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery


Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains.


We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90.


A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed.


Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.)


Remote Ischemic Preconditioning in Cardiac Surgery — Ineffective and Risky?


Every year millions of patients undergo cardiac surgery, which may be associated with short- and long-term cardiovascular complications in as many as 20% of patients. Although the perioperative care of patients undergoing cardiac surgery has become highly sophisticated and is facilitated by the availability of guidelines, there is ample room to improve clinical outcomes. However, the search for a magic bullet — a cardioprotective strategy that could be successfully administered in addition to the current standard treatment to provide additional benefits — is tantalizing but frustrating, as evidenced by the negative results of two trials of remote ischemic preconditioning in cardiac surgery now reported by Hausenloy et al.1 and by Meybohm et al.2 in the Journal.

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