CONDI-2/ERIC-PPCI Puts the Kibosh on Ischemic Conditioning in STEMI

The results may be “emphatic,” but there may still be subgroups who could benefit from myocardial salvage, the discussant said.

CONDI-2/ERIC-PPCI Puts the Kibosh on Ischemic Conditioning in STEMI

PARIS, France—Remote ischemic conditioning (RIC) does not offer any clinical outcome benefit among STEMI patients undergoing primary PCI, according to results of the CONDI-2/ERIC-PPCI study presented here today in a Hot Line session at the European Society of Cardiology Congress 2019.

Prior studies in this space have been limited and small, but this analysis “provides definitive evidence” with regard to RIC in the setting of contemporary primary PCI, said Hans Erik Bøtker, MD, PhD (Aarhus University Hospital, Denmark), during his presentation. “That's unfortunate because until now, RIC has been the most promising cardioprotective strategy for improving clinical outcome following STEMI. So we now need to identify novel cardioprotective strategies and innovative approaches to cardioprotection in STEMI patients undergoing primary PCI and that might include a combination of multitarget therapies.”

For the analysis, researchers randomized 5,401 STEMI patients slated to undergo primary PCI from two study populations—CONDI-2 and ERIC-PPCI—at 33 centers in Denmark, Serbia, Spain, and the United Kingdom to balloon dilatation and stenting with or without remote ischemic conditioning either in the ambulance or on hospital admission. The conditioning procedure was performed through intermittent arm ischemia via four cycles of 5-minute inflation followed by 5-minute deflation of a blood-pressure cuff.

After 1 year of follow-up, there was no difference between the control and study groups with regard to the primary composite endpoint of cardiac death or heart failure hospitalization (8.6% vs 9.4%; HR 1.10; 95% CI 0.91-1.32). There were also no differences in the composite secondary endpoints of cardiac death and heart failure hospitalization at 30 days, and MACCE at 30 days and 1 year.

Results were maintained throughout subgroup analyses by age, diabetes status, infarct location, TIMI flow, and time elapsed from first medical contact to balloon. There was also no difference in high-sensitivity troponin T release between the groups, which indicates that there was no visible reduction in infarct size by RIC, said Bøtker.

‘Hopefully’ Not the End of the RIC Road

“I would not be quite honest if I didn't admit that we were somewhat disappointed about these results, given the promising results that we have seen in the majority of previous proof-of-concept trials,” said Bøtker during the session, adding that he can only guess as to why RIC didn’t work here.

Other RIC studies as well as those have looked at using pharmacologic compounds—like exenatide (Bydureon; Vidal) and cyclosporin—as well as mechanical approaches—like local postconditioning and reinflating the balloon in the coronary artery—to increase myocardial salvage in STEMI patients. But so far they have only established proof of concept and seem to have no effect on clinical outcomes, he said. “You can speculate why that is the case . . . and perhaps the explanation is that most STEMI patients fare so well nowadays with their outcomes that the magnitude of the target, reperfusion injury, is too small to translate into a clinical benefit,” Bøtker said.

It’s also possible that the follow-up period of this study wasn’t substantial enough to adequately evaluate clinical benefit of cardiac ischemic conditioning, he added.

Bernard Gersh, MB, ChB, DPhil (Mayo Clinic, Rochester, MN), who discussed the study during the session, called it a “very well-executed, large pivotal trial.”

“Nonetheless, the results of this trial are emphatic, and there appears to be no role for routine remote ischemic preconditioning in the management of most—and I will emphasize most, perhaps not all, but most—patients with STEMI undergoing primary PCI,” he continued. “The results may not be what we’d hoped to hear, and I share Dr. Bøtker’s disappointment, but the data appear to be conclusive in regard to the majority of the primary PCI population.”

It’s possible that the window of opportunity for myocardial salvage is limited, and “when you have the cardiac mortality, as in this trial, of about 2%, it’s very difficult to even demonstrate a difference even if you can make a small difference,” said Gersh. “That's the era that we now live in.”

Still, there may be subgroups of STEMI patients who may still benefit, he guessed, namely those with cardiogenic shock but no cardiac arrest for whom the mortality rate has been around 23% in previous studies.

“It’s been a very long and bumpy and perhaps frustrating road,” Gersh concluded. “Have we come to the end? I hope not.”

Sources
  • Bøtker HE. Effect of remote ischaemic conditioning on clinical outcomes in patients with STEMI undergoing primary PCI: the CONDI-2/ERIC-PPCI trial. Presented at: ESC 2019. September 1, 2019. Paris, France.

Disclosures
  • CONDI-2/ERIC-PPCI was funded by the British Heart Foundation, University College London, Danish Innovation Foundation, Novo Nordisk Foundation, and Trygfonden.
  • Bøtker reports holding stock in CellAegis.

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