Remote Preconditioning Before CABG Reduces Not Only Myocardial Injury but Also Mortality

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Patients who undergo remote ischemic preconditioning prior to elective coronary artery bypass graft (CABG) surgery not only obtain perioperative myocardial protection but also have better long-term prognosis. The findings, from a randomized controlled trial, appear in the August 17, 2013, issue of the Lancet.

Gerd Heusch, MD, PhD, of the University of Essen Medical School (Essen, Germany), and colleagues enrolled 329 patients scheduled to undergo elective, isolated first-time CABG under cold crystalloid cardioplegia and cardiopulmonary bypass at the West German Heart Centre (Essen, Germany) between April 2008 and October 2012. Patients were randomized to remote ischemic preconditioning (3 cycles of 5-minute blood pressure cuff inflations and deflations on the upper left arm while under anesthesia; n = 162) or no added treatment (n = 167).

Baseline characteristics were similar between groups, and no safety concerns arose related to remote ischemic preconditioning.

Myocardial Injury, Long-term Outcomes Affected

Perioperative myocardial injury (primary endpoint; mean area under the curve for concentration of cardiac troponin I over 72 hours) was reduced for preconditioning patients compared with controls at 266 ng/mL (95% CI 237-298 ng/mL) vs. 321 ng/mL (95% CI 287-360 ng/mL), an estimated ratio of 0.83 (95% CI 0.70-0.97; P = 0.022).

In the main intention-to-treat analysis, the prevalence of troponin I concentrations greater than 30 ng/mL was lower after preconditioning, as was perioperative MI (type 5). All-cause mortality was lower at 1 year. MI rates also were reduced, while rates of cardiac death, stroke, and MACCE (postoperative MI and TIA or stroke) all showed trends favoring preconditioning (table 1). Repeat revascularization rates were similar between the 2 groups.

Table 1. Perioperative and Clinical Outcomes

By the end of follow-up at more than 4 years after CABG, the 1-year reductions in all-cause mortality and MACCE were sustained, as was the trend toward less cardiac death. Per-protocol analysis also showed a reduction in cardiac troponin I release but no protection against mortality over the long-term.

Building on previous research showing that remote ischemic preconditioning reduces perioperative myocardial injury during elective CABG, the current study shows “a persistent benefit” from the treatment, the paper notes. Dr. Heusch and colleagues acknowledge several limitations to the study, including its single-center design and lack of power to detect clinical outcomes. Moreover, the patient population was at low risk of adverse events.

Cardioprotection and Beyond

Dr. Heusch told TCTMD in an e-mail communication that the researchers were “indeed surprised that a moderate troponin reduction translated into such marked reduction in all-cause and more specifically cardiovascular mortality.” Importantly, he said, “protection by remote preconditioning goes beyond cardioprotection, insofar as postoperative kidney function is better acutely and also stroke and sepsis occur less frequently during follow-up.”

Dr. Heusch advised that preconditioning is less beneficial in conjunction with propofol rather than isoflurane anesthesia. “Whether protection is attenuated in diabetes is currently not clear and under investigation,” he added.

Yet there are no known drawbacks to the treatment, Dr. Heusch said. “From our perspective, remote preconditioning is ready for clinical use: It is safe and effective, simple, and cheap. However, the underlying mechanistic signal transduction is still largely unclear and deserves further investigation.”

One such trial is ERICCA, a United Kingdom-based study slated to enroll over 1,600 CABG patients at 28 centers.

An editorial accompanying the paper by Nathan Mewton, MD, of Université Claude Bernard Lyon (Lyon, France), and Michel Ovize, MD, PhD, of Hôpital L. Pradel, Hospices Civils de Lyon (Lyon, France), also points to the RIPHeart-Study, which aims to enroll approximately 2,000 patients undergoing CABG in Germany.

“The exciting findings of [the Lancet paper] need to be supported by strong experimental evidence and elucidation of the mechanisms underlying the effects of remote conditioning,” they say, agreeing that the benefits of preconditioning likely extend beyond the heart itself.

‘Low Tech and Cheap’

In an e-mail communication, Robert A. Kloner, MD, PhD, of Good Samaritan Hospital (Los Angeles, CA), described the paper as “very exciting, indeed.”

Dr. Kloner pointed out that, in 1993, his research group was the first to describe the phenomenon of remote preconditioning. “Since then there have been well over a hundred clinical trials looking at remote ischemic conditioning in situations of CABG, PCI, and acute myocardial infarction. The results of these studies have been somewhat mixed, with some studies being positive and others negative,” he said, describing the new research as “very carefully done.”

According to Dr. Kloner, the findings “show that a low-tech and cheap therapy can further reduce cardiac damage during CABG. . . . It is nice to see a concept such as remote ischemic conditioning that was developed in the laboratory translate to a clinically relevant benefit to patients.”

 

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Sources:
1. Thielmann M, Kottenberg E, Kleinbongard P, el. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: A single-centre randomised, double-blind, controlled trial. Lancet. 2013;382:597-604.

2. Mewton N, Ovize M. Remote preconditioning and all-cause mortality [editorial]. Lancet. 2013;382:579-580.

 

 

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