Remote Ischemic Preconditioning in Noncardiac Surgery: The End of a Promising Hypothesis?

Postoperative myocardial injury remains a major determinant of morbidity and mortality after noncardiac surgery, prompting sustained interest in preventive strategies such as Remote Ischemic Preconditioning (RIPC). Initially supported by compelling experimental data and numerous small-randomized trials, RIPC has been widely perceived as a low-cost, low-risk intervention with potential systemic organ-protective effects. The PRINCE randomized clinical trial represents the most rigorous and definitive evaluation of RIPC in this setting to date. Conducted across 25 centres in eight countries and enrolling more than 1,200 high-risk patients, PRINCE used a double-blind, sham-controlled design, avoided propofol anaesthesia, and selected postoperative myocardial injury, defined by troponin elevation as a clinically meaningful primary endpoint. The trial demonstrated no reduction in myocardial injury or secondary outcomes, including myocardial infarction, stroke, acute kidney injury, or mortality, with RIPC compared with sham treatment. Moreover, modest safety signals, including increased limb petechiae and hospital readmissions, further weaken the rationale for routine use. This editorial place PRINCE in the broader context of perioperative research, highlighting the recurrent discordance between small, single-centre trials and large multicentre randomized studies. The findings decisively challenge the clinical utility of RIPC in noncardiac surgery and underscore the importance of adequately powered methodologically robust trials before adopting biologically appealing interventions into standard perioperative practice.