Remote ischemic preconditioning does not improve cardiac surgery outcomes

Remote ischemic preconditioning failed to improve clinical outcomes after elective cardiac surgery, according to two studies published in The New England Journal of Medicine.

The RIPHeart trial showed no benefit of remote ischemic preconditioning in patients undergoing elective cardiac surgery, and the ERICCA trial showed no benefit for it in patients undergoing elective on-pump CABG, sometimes coupled with valve surgery. The results of ERICCA were previously presented at the American College of Cardiology Scientific Sessions.

RIPHeart study

Researchers for the RIPHeart study randomly assigned 1,403 patients undergoing elective cardiac surgery that required cardiopulmonary bypass and total anesthesia with IV propofol. After anesthesia but before surgery, patients received upper-limb remote ischemic preconditioning or a sham procedure. Remote ischemic preconditioning consisted of four cycles of upper-limb ischemia, defined as 5-minute BP-cuff inflation to at least 200 mm Hg followed by 5-minute deflation.

The primary endpoint was a composite of death, MI, stroke or acute renal failure by hospital discharge. Secondary endpoints were the individual components of the primary endpoint at 90 days.

Patrick Meybohm, MD, MHBA, from the department of anesthesiology, intensive care medicine and pain therapy at University Hospital Frankfurt, Germany, and colleagues found no difference between the groups in the primary outcome (intervention group, 14.3%; sham group, 14.6%; P = .89).

The results also showed no difference in any secondary outcomes (death: intervention group, 1.3% vs. sham group, 0.6%; P = .21; MI: 6.8% vs. 9.1%; P = .12; stroke: 2% vs. 2.2%; P = .79; acute renal failure: 6.1% vs. 5.1%, respectively; P = .45).

The researchers also observed no differences in troponin release level, duration of mechanical ventilation, overall or ICU length of stay, new-onset atrial fibrillation and postoperative delirium. No adverse events related to remote ischemic preconditioning were observed.

ERICCA study

Researchers for the ERICCA study randomly assigned 1,612 patients undergoing on-pump CABG with blood cardioplegia with or without valve surgery to remote ischemic preconditioning or sham conditioning. Remote ischemic preconditioning was performed in the same manner as in the RIPHeart study.

The primary endpoint was a composite of CV death, nonfatal MI, coronary revascularization or stroke at 12 months.

Derek J. Hausenloy

Derek J. Hausenloy, MBChB, PhD, FACC, from the Hatter Cardiovascular Institute at University College London, and colleagues found no difference in the primary outcome between the groups (intervention group, 26.5%; sham group, 27.7%; HR = 0.95; 95% CI, 0.79-1.15).

The groups also had similar rates of adverse events, perioperative myocardial injury, inotrope score, acute kidney injury, overall and ICU length of stay, 6-minute walk distance and quality of life.

Questions about risk

Remote ischemic preconditioning failed to improve outcomes in two large-scale, randomized, sham-controlled trials despite positive results in smaller clinical studies and animal studies, Michael Zaugg, MD, MBA, and Eliana Lucchinetti, PhD, from the University of Alberta, Edmonton, wrote in an accompanying editorial.

A possible explanation, according to Zaugg and Lucchinetti, is that “it is likely that such preconditioning is less effective in patients with infarct-remodeled hearts or diabetes and in older patients than in patients without those risk factors.” Other explanations may be that since CABG itself is protective, “perhaps further protection is impossible to achieve” or concomitant medications may interfere with the preconditioning process.

Zaugg and Lucchinetti also expressed concern about a trend toward higher CV death in the remote ischemic preconditioning group in the ERICCA trial (P = .08).

“In view of these findings, one might ask whether remote ischemic conditioning may even be risky — specifically, in certain patients with highly unstable coronary plaques,” Zaugg and Lucchinetti concluded. – by Erik Swain

References:

Hausenloy DJ, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1413534.

Meybohm P, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1413579.

Zaugg M, Lucchinetti E. N Engl J Med. 2015;doi:10.1056/NEJMe1510338.

Disclosures: Lucchinetti, Meybohm, Hausenloy and Zaugg report no relevant financial disclosures. See the full studies for a list of the other researchers’ relevant financial disclosures.