Long‐term outcome following remote ischemic postconditioning during percutaneous coronary interventions—the RIP‐PCI trial long‐term follow‐up

Abstract

The clinical value of ischemic conditioning during percutaneous coronary intervention (PCI) and mode of administration is controversial. Our aim was to assess the long-term effect of remote ischemic postconditioning among patients undergoing PCI. We randomized 360 patients undergoing PCI who presented with a negative troponin T at baseline into 3 groups: 2 groups received remote ischemic postconditioning (with ischemia applied to the arm in 1 group and to the thigh in the other group), and the third group acted as a control group. Remote ischemic postconditioning was applied during PCI immediately following stent deployment, by 3, 5-minute cycles of blood pressure cuff inflation to >200 mm Hg on the arm or thigh (20 mm Hg to the arm in the control), with 5-minute breaks between each cycle. There were no differences in baseline characteristics among the 3 groups. Periprocedural myocardial injury occurred in 33% (P = 0.64). After 1 year, there was no difference between groups in death (P = 0.91), myocardial infarction (P = 0.78), or repeat revascularization (P = 0.86). During 3 years of follow-up, there was no difference in death, myocardial infarction, and revascularization among the groups there is a debate regarding the prognostic implications of minor periprocedural infarcts, and suggestions for using more restrictive definitions, 4 many reports suggest that even a minor degree of elevation in cardiac markers, either pre-or postprocedure, can have longterm prognostic implications. 5-7 Some investigators consider alleviating periprocedural myocardial injury as a therapeutic target for cardioprotection. 8 One potential method of cardioprotection during PCI is ischemic conditioning. 9,10 The concept of ischemic conditioning for cardioprotection, is that brief, repeated episodes of ischemia and reperfusion, render the heart to be more resistant to subsequent ischemia-reperfusion episodes. 10 The mechanism involves complex neuronal and humoral signal transduction pathways. 11Whereas the effects of ischemic conditioning in animal studies were impressive, even if applied remotely 12 or after the initial ischemic injury (postconditioning), 13 the results from human studies were less consistent. In patients undergoing PCI, remote ischemic preconditioning (RIPre) induced by cyclic prolonged blood pressure cuff inflation on the arm prior to PCI was associated with a decrease in periprocedural myocardial injury, which later translated into a decrease in cardiac events. 14,15 The beneficial effect of RIPre in the setting of PCI was also confirmed in meta-analyses. 16,17 However, in a large meta-analysis that included application of ischemic conditioning in multiple settings, overall ischemic conditioning had no effect on major cardiovascular outcomes, 18 and so far we have not witnessed the translation of ischemic conditioning into clinical practice. 19

Ischemic postconditioning during primary percutaneous coronary interventions—not ready for prime time

“…It is possible that ischemic conditioning might not be effective in humans. This is supported by many recent trials (8,21,24).…”

“…The effect of ischemic conditioning as a way of myocardial protection seemed initially promising with many small studies demonstrated dramatic effect. However, as more data is gathered, the benefit of ischemic conditioning seems more controversial (7,8).…”

Endothelial cell-derived exosomes protect SH-SY5Y nerve cells against ischemia/reperfusion injury

“…A possible mechanism is thought to be associated with endothelial dysfunction in cerebral ischemia ( 7 ). Remote ischemic postconditioning (RIP) in the treatment of CVD relieves ischemia/reperfusion (I/R) injury ( 8 – 10 ). However, it is not known if RIP induces neuroprotection against cerebral ischemia and what the underlying mechanism is.…”

Cardioprotection during ischemia by coronary collateral growth

“…Because reperfusion injury plays a significant role in a patient's outcome, a great deal of focus has been directed toward cardioprotection by ischemic pre-, per-, and postconditioning, yielding disparate results in terms of potential therapies. Although pharmacological approaches have not translated into therapies (26) and most postconditioning trials have not produced positive outcomes (12,32), some recent trials using perconditioning strategies have shown promise (44).…”