C ardiac R emote I schemic P reconditioning Prior to E lective Vascular S urgery (CRIPES): A Prospective, Randomized, Sham‐Controlled Phase II Clinical Trial

Abstract

BackgroundRemote 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 ResultsCardiac 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).ConclusionsIn 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.

Diagnosis and Management of Patients With Myocardial Injury After Noncardiac Surgery: A Scientific Statement From the American Heart Association

“…69 In contrast, in the larger, sham-controlled CRIPES study (Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery), ischemic preconditioning did not reduce the incidence of MINS (22.2% versus 24.7%; P =0.67). 70 Thus, current evidence does not support a benefit of ischemic preconditioning to prevent MINS.…”

Clinical translation of myocardial conditioning

“…Noncardiac surgery. In major noncardiac surgery, RIC has mainly been applied to high-risk procedures such as vascular surgery (7,36,70,93,165,(302)(303)(304). The protective effect of RIC seems to be modest with the use of a variety of outcome measure (Table 4).…”

Preventing Myocardial Injury Following Non-Cardiac Surgery: A Potential Role for Preoperative Antioxidant Therapy with Ubiquinone

“…In a randomized controlled study involving over 500 veterans undergoing elective vascular surgery and 20 medical centers within the Veterans Affair (VA) health care system, we demonstrated that a strategy of preoperative coronary artery revascularization before an elective vascular surgery did not reduce the long-term risk of death at 2.7 years following the operation [ 4 ]. Using an additional preoperative strategy with a preconditioning protocol, we also failed to reduce the incidence of postoperative elevations in cardiac troponin [ 5 ]. Other randomized controlled trials have tried to reduce adverse perioperative outcomes and have targeted well-accepted risk factors among patients undergoing elective surgery, including pharmacological agents that are known to reduce secondary outcome measures in patients with coronary artery disease.…”