AT ACC 2015

SAN DIEGO (FRONTLINE MEDICAL NEWS)Remote ischemic preconditioning failed to improve long-term clinical outcomes in higher-risk patients undergoing coronary artery bypass surgery in the ERICCA trial.

At 1 year, there were no differences between patients receiving remote ischemic conditioning (RIC) or a sham procedure in the combined primary endpoint of cardiovascular death, MI, stroke, and coronary revascularization (27% vs. 28%) or its individual components.

Only the extent of perioperative myocardial injury, measured as area under the curve troponin T levels, at 72 hours was significantly lower with RIC (median 30.1 ng.h/mL vs. 35.7 ng.h/mL), principal investigator Dr. Derek Hausenloy reported at the annual meeting of the American College of Cardiology.

The simple, low-cost intervention consisted of four 5-minute blood pressure cuff inflations to 200 mm Hg and deflations immediately before patients went on bypass.

Multiple proof-of-concept studies have shown that brief, reversible episodes of ischemia followed by reperfusion reduces the extent of perioperative myocardial injury in patients undergoing elective coronary artery stenting or bypass grafting.

“In the setting of cardiac bypass surgery, the cardioprotective effect presented by RIC, or remote ischemic conditioning, may be affected by factors during surgery,” said Dr. Hausenloy of University College, London.

There are multiple causes of injury in patients undergoing bypass that include not only myocardial reperfusion injury, but also coronary microembolization, inflammation as the patient is taken on and off bypass, and direct injury to the heart, he noted.

ERICCA (Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Graft Surgery) also focused on a higher-risk aged population (76 years) with high rates of comorbidities like diabetes (25%) and hypertension (75%) that have been shown to impact RIC and other conditioning strategies.

Discussant Dr. Richard Fogel of St. Vincent Heart Center in Indianapolis, suggested RIC may not have worked because of a dose-response issue and questioned whether the results would have been different had the investigators, for example, done six inflations for 10 minutes each or performed RIC the day before.

Discussant Dr. Eric Bates of the University of Michigan in Ann Arbor, suggested that as long as patients are anesthetized, prolonged conditioning immediately before and after surgery might be considered.

“The RIC protocol has not been very well characterized, although most of the prior studies used three or four cycles,” Dr. Hausenloy said. “Whether this is the optimal stimulus is not known or clear.”

ERICCA enrolled 1,612 patients with an additive Euroscore of at least 5 who underwent CABG using blood cardioplegia at 29 centers in the United Kingdom. Of these, 801 received RIC and 811 received sham, simulated BP cuff inflations/deflations.

One year after surgery, the RIC and control groups had similar rates of major adverse cardiac and cerebral events, at 26.7% and 27.7%, respectively; cardiovascular death, at 5.9% and 3.9%; MI, at 21.8% and 23.7%; stroke, at 2.1% and 2.0%; and revascularization, at 0.2% and 0.4%.

“It’s interesting that we show a modest effect on reducing perioperative myocardial injury, but we didn’t see any associated improvement in clinical outcome,” he said. “This may question the use of perioperative myocardial injury, as measured by serum biomarkers, as a surrogate marker of cardioprotection. However, the caveat is that we only have a complete dataset for this conclusion in half the patients.”

The potential effect of RIC remains to be investigated in other settings of ischemia and reperfusion injury such as patients with ST-segment elevation MI or undergoing organ transplantation, Dr. Hausenloy said.

“Clearly in these settings of STEMI and organ transplantation, the contribution of ischemia reperfusion injury is greater, and one may speculate that the effect of RIC may be greater,” he added.