Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery (CRIPES): A Prospective, Randomized, Sham-Controlled Phase II Clinical Trial

Santiago Garcia, Thomas S Rector, Marina Zakharova, Rebekah R Herrmann, Selcuk Adabag, Stefan Bertog, Yader Sandoval, Steve Santilli, Emmanouil S Brilakis, Edward O McFalls, Santiago Garcia, Thomas S Rector, Marina Zakharova, Rebekah R Herrmann, Selcuk Adabag, Stefan Bertog, Yader Sandoval, Steve Santilli, Emmanouil S Brilakis, Edward O McFalls

Abstract

Background: Remote ischemic preconditioning (RIPC) has been shown to reduce infarct size in animal models. We hypothesized that RIPC before an elective vascular operation would reduce the incidence and amount of a postoperative rise of the cardiac troponin level.

Methods and results: Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery (CRIPES) was a prospective, randomized, sham-controlled phase 2 trial using RIPC before elective vascular procedures. The RIPC protocol consisted of 3 cycles of 5-minute forearm ischemia followed by 5 minutes of reperfusion. The primary endpoint was the proportion of subjects with a detectable increase in cardiac troponin I (cTnI) and the distribution of such increases. From June 2011 to September 2015, 201 male patients (69±7, years) were randomized to either RIPC (n=100) or a sham procedure (n=101). Indications for vascular surgery included an expanding abdominal aortic aneurysm (n=115), occlusive peripheral arterial disease of the lower extremities (n=37), or internal carotid artery stenosis (n=49). Of the 201 patients, 47 (23.5%) had an increase in cTnI above the upper reference limit within 72 hours of the vascular operation, with no statistically significant difference between those patients assigned to RIPC (n=22; 22.2%) versus sham procedure (n=25; 24.7%; P=0.67). Among the cohort with increased cTnI, the median peak values (interquartile range) in the RIPC and control group were 0.048 (0.004-0.174) and 0.017 (0.003-0.105), respectively (P=0.54).

Conclusions: In this randomized, controlled trial of men with increased perioperative cardiac risks, elevation in cardiac troponins was common following vascular surgery, but was not reduced by a strategy of RIPC.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01558596.

Keywords: remote preconditioning; troponins; vascular surgery.

© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1
Figure 1
Flow diagram of study patients. RIPC indicates remote ischemic preconditioning.
Figure 2
Figure 2
Primary endpoint: proportion with cardiac troponin I (cTnI) increases. RIPC indicates remote ischemic preconditioning.
Figure 3
Figure 3
Distribution of cardiac troponin I according to assigned treatment. RIPC indicates remote ischemic preconditioning.

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