Preconditioning, Postconditioning Join Forces to Limit STEMI Damage

PARIS, France—Combining remote ischemic conditioning with postconditioning in STEMI patients undergoing PCI is feasible and increases myocardial salvage over standard care. But the same benefit is not seen with postconditioning alone, according to data from the LIPSIA-CONDITIONING trial presented May 19, 2015, at EuroPCR.

Prompt reperfusion during STEMI can protect the myocardium and reduce the risk of cardiovascular events, but it may also cause reperfusion injury, said researcher Ingel Eitel, MD, of Heart Center Leipzig (Leipzig, Germany), in his presentation. Given that animal models suggest such “injury accounts for up to 50% of the final infarct size,” he continued, it is “an important treatment target.”

According to Dr. Eitel, the “most powerful intervention” appears to be conditioning, which consists of brief episodes of ischemia and reperfusion either before or after PCI. “Recent evidence suggests that postconditioning and remote ischemic conditioning share some but not all mechanistic signaling pathways, and therefore the combination of these 2 conditioning stimuli may result in better cardioprotection [than either therapy alone],” he explained.

LIPSIA-CONDITIONING randomized 696 STEMI patients within 12 hours of symptom onset to receive:

• Combined remote ischemic conditioning via upper-arm cuff immediately after hospitalization/randomization, followed by postconditioning at the culprit lesion immediately after reperfusion during primary PCI (n = 232)
• Postconditioning alone (n = 232)
• Standard PCI (control; n = 232)

Baseline characteristics were well balanced among the 3 groups.

Better Myocardial Salvage, ST-Segment Resolution

Myocardial salvage index (primary endpoint) was measured on day 1-4 using CMR and assessed by a core lab, with full results available for 71% of the original cohort.

Index value was higher for the combined therapy group than for the control group at approximately 48% vs 38% (P = .024), with a treatment effect that was “consistent across all important subgroups,” Dr. Eitel reported. However, there were no differences between the 2 conditioning arms (P = .16) or between postconditioning and standard PCI (P = .38).

No differences across groups were seen for infarct size, microvascular obstruction, or peak creatine kinase. ST-segment resolution was greater with combined therapy than with standard PCI at approximately 70% vs 62% (P = .046), and again postconditioning alone offered no benefit (P = .51).

At 6 months, the composite of death, reinfarction, and new congestive heart failure occurred with equal frequency among the 3 groups (log-rank P = .44).

Clinical Relevance Yet to Be Determined

“A combined intrahospital [protocol for remote ischemic conditioning and postconditioning] is clinically feasible and effective in increasing myocardial salvage as compared to conventional PCI,” Dr. Eitel concluded. “Our data indicate that combined [treatment has] additive cardioprotective effects, and therefore [the therapy] should be further investigated in future well-designed clinical trials powered for clinical outcome.”

Panelist Michel Ovize, MD, PhD, of Hôpital Louis Pradel (Lyon, France), pointed out that strategies affecting infarct size also influence edema, questioning whether this might account for the lack of difference in myocardial salvage observed by CMR for postconditioning alone.

“That is an important comment,” Dr. Eitel agreed, citing research that suggests edema is also reduced by cardioprotective strategies, including postconditioning. But data come from smaller studies, he noted, and in LIPSIA-CONDITIONING, no differences in the myocardium at risk were observed among the 3 groups.

William Wijns, MD, PhD, of Cardiovascular Center Aalst (Aalst, Belgium), who co-chaired the session, asked whether the differences in myocardial salvage were actually clinically relevant.

Not at 6 months, Dr. Eitel said, “but probably we need to wait longer [to see] if the increase in myocardial salvage may translate into improved outcomes at later time points.”

Source: 
Eitel I. Randomized comparison of combined ischemic pre- and postconditioning versus postconditioning versus control in patients with STEMI: the LIPSIA-CONDITIONING trial. Presented at: EuroPCR; May 19, 2015; Paris, France.

Disclosures:

• Dr. Eitel’s presentation contained no statement regarding potential conflicts of interest.

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