Delayed Postconditioning Ineffective in STEMI Patients Undergoing Primary PCI

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Mechanical ischemic postconditioning after percutaneous coronary intervention (PCI) does not reduce infarct size among patients with ST-segment elevation myocardial infarction (STEMI) who have spontaneous reperfusion of the culprit vessel at the time of admission. The findings, from a multicenter randomized trial, were published online February 28, 2014, ahead of print in the European Heart Journal.

Michel Ovize, MD, PhD, of Hôpital Louis Pradel (Lyon, France), and colleagues looked at 90 STEMI patients who presented within 12 hours of symptom onset and had TIMI flow grade 2-3 at the time of admission. Patients first underwent direct stenting of the culprit lesion then received standard care (n = 46) or postconditioning (n = 44), during which the angioplasty balloon was re-inflated in 4 cycles (1-minute inflation/1-minute deflation) within 1 minute after stenting.

Baseline characteristics were similar between the 2 groups, and both cohorts had comparable mean values for area at risk (approximately 38% of LV circumference; P = 0.89) and time from chest pain onset to intervention (slightly over 4 hours; P = 0.93).

Yet postconditioning failed to reduce infarct size on cardiac magnetic resonance (CMR) imaging (primary endpoint) or affect biomarker release (table 1). Findings remained similar after adjustment for area at risk.

Table 1. Measures of Infarct Size

 

Postconditioning
(n = 44)

Controls
(n = 46)

P Value

CMR Infarct Size, g

21 ± 18

23 ± 17

0.64

Creatine Kinase
Area Under the Curve, AU
Peak, IU/L

 
42,901 ± 34,463
1,580 ± 1,491

 
47,424 ± 36,246
1,755 ± 1,360

 
0.49
0.41

Troponin I
Area Under the Curve, AU
Peak, µg/L

 
1,988 ± 2,296
87 ± 140

 
1,941 ± 1,637
70 ± 63

 
0.52
0.45

No adverse events related to postconditioning occurred, nor was there any difference in clinical outcomes at 6 months between the study arms (P = 0.36).

Timing, Other Details Key to Benefit

In an email, Dr. Ovize told TCTMD that he is unsurprised by the results. “Large experimental evidence suggests that the time window for protection by postconditioning is very narrow after reflow,” he noted. “Yet, a couple of studies had showed that application of postconditioning with some delay would still be protective. This question is of importance in clinical practice for PCI cardiologists. Here we found no significant benefit, confirming most of the preclinical findings.”

The current study “suggests that PCI (and likely pharmacological postconditioning) [must be applied] before or at the time of reopening of the culprit coronary artery,” Dr. Ovize explained. “In other words, patients admitted with a TIMI flow > 1 likely will not benefit from protective intervention, while TIMI 0-1 patients can still get protection. In several negative past studies, this type of inclusion criteria has not been carefully considered. We now know that it is key.”

Future studies should focus on whether a given intervention is protective in a particular subpopulation, he suggested, adding, “Selection of study population is a crucial issue. We have a good example here. STEMIs are a heterogenous population and investigators ought to pay attention to inclusion criteria, including TIMI flow at admission, collateral circulation, size of the risk region, [and] timing of administration of the protective intervention.”

Joo-Yong Hahn, MD, of Samsung Medical Center (Seoul, South Korea), told TCTMD in an email that the current findings make sense. “It is unlikely that ischemic postconditioning is beneficial in patients with TIMI flow grade 2-3, in whom reperfusion injury may be not substantial.”

In the POST trial, for which he served as an investigator, ischemic postconditioning did not improve myocardial reperfusion or clinical outcomes, Dr. Hahn pointed out. POST “was the largest study on this issue until now,” he said. “Cardioprotective effect of ischemic postconditioning seems to be modest, at best, in patients undergoing primary PCI with current standard practice.”

Also in an email, Giuseppe Tarantini, MD, PhD, of the University of Padua (Padua, Italy), stressed to TCTMD that the current study pushes the “(pathophysiologic) envelop” too far.

“It is counterintuitive why postconditioning should have worked when [reperfusion] of the infarct-related artery has already happened,” he said, noting that the “jury is still out” on whether the method works even in patients who present early with occluded arteries. “Moreover, in the absence of a concrete rationale it seems imprudent to apply a technique that may increase microembolization,” Dr. Tarantini added.

Other Conditioning Options Being Explored

Pharmacological postconditioning in addition to PCI still merits a phase III trial to determine clinical benefit, Dr. Ovize said.

Unlike mechanical ischemic postconditioning, “both remote and pharmacological conditioning can be initiated before coronary angiography, as early as at the time of first medical care or during the ambulance transfer to the hospital,” the researchers note in the paper. “This is a major advantage that also opens the opportunity to treat 2-3 TIMI flow patients and have them benefit from protective interventions against lethal reperfusion injury. This, however, remains to be demonstrated.”




Source:
Roubille F, Mewton N, Elbaz M, et al. No post-conditioning in the human heart with thrombolysis in myocardial infarction flow 2-3 on admission. Eur Heart J. 2014;Epub ahead of print.

 

 

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Disclosures
  • Drs. Ovize and Hahn report no relevant conflicts of interest.

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