Effect of Ischemic Postconditioning on Infarct Size in Patients With ST‐Elevation Myocardial Infarction Treated by Primary PCI Results of the POSTEMI (POstconditioning in ST‐Elevation Myocardial Infarction) Randomized Trial

Abstract

BackgroundReduction of infarct size by ischemic postconditioning (IPost) has been reported in smaller proof‐of‐concept clinical studies, but has not been confirmed in other smaller studies. The principle needs to be evaluated in larger groups of ST‐elevation myocardial infarction (STEMI) patients before being implemented in clinical practice. This study assessed the effect of ischemic postcoditioning (IPost) on infarct size in patients with STEMI treated by primary percutaneous coronary intervention (PCI).Methods and ResultsPatients with first‐time STEMI, <6 hours from symptom onset, referred to primary PCI were randomized to IPost or control groups. IPost was administered by 4 cycles of 1‐minute reocclusion and 1‐minute reperfusion, starting 1 minute after opening, followed by stenting. In the control group, stenting was performed immediately after reperfusion. The primary endpoint was infarct size measured by cardiac magnetic resonance after 4 months. A total of 272 patients were randomized. Infarct size (percent of left ventricular mass) after 4 months (median values and interquartile range) was 14.4% (7.7, 24.6) and 13.5% (8.1, 19.3) in the control group and IPost group, respectively (P=0.18). No significant impact of IPost was found when controlling for baseline risk factors of infarct size in a multivariate linear regression model (P=0.16). The effects of IPost on secondary endpoints, including markers of necrosis, myocardial salvage, and ejection fraction, as well as adverse cardiac events during follow‐up, were consistently neutral.ConclusionsIn contrast to several smaller trials reported previously, we found no significant effects of IPost on infarct size or secondary study outcomes.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov Unique identifier: NCT.No.PO1506.

Time to Give Up on Cardioprotection?

“…[73][74][75][76][77][78][79][81][82][83]86,[91][92][93] In most of the studies, the patient cohorts were small; of note, the 3 studies with the largest patient cohorts were neutral with respect to infarct size. 90,94,96 All studies in adult 97,98 or pediatric [99][100][101][102][103] cardiac surgery reported a significant infarct size reduction, as reflected by biomarker (creatine kinase-muscle brain, and troponin) release. A consistent reduction of infarct size by biomarker release and by imaging was confirmed in recent meta-analyses.…”

“…The 3 trials on ischemic postconditioning with the largest patient cohorts were neutral with respect to infarct size and clinical outcome. 90,94,96 With respect to the above criteria to identify a cardioprotective intervention, a straightforward explanation emerges: different from the original proof-of-concept studies of Ovize and collaborators, 73 either the time from symptom onset was longer, that is, within 12 90,96 rather than 6 hours, or no direct stenting was used. 90,94 As outlined earlier, little protection is expected after 12 hours of coronary occlusion.…”

“…90,94,96 With respect to the above criteria to identify a cardioprotective intervention, a straightforward explanation emerges: different from the original proof-of-concept studies of Ovize and collaborators, 73 either the time from symptom onset was longer, that is, within 12 90,96 rather than 6 hours, or no direct stenting was used. 90,94 As outlined earlier, little protection is expected after 12 hours of coronary occlusion. 19,20,230,231 Direct stenting avoids coronary microembolization and further myocardial injury by manipulation of the culprit coronary lesions, 243 which may obscure the otherwise protective effect of ischemic postconditioning.…”

Postconditioning of ischemic heart by intermittent ventricular pacing at the beginning of reperfusion: novel mechanisms and potential utilities in interventional cardiology settings

“…It is noteworthy that while there is mounting evidence for the cardioprotective efficacy of postconditioning in normal individuals of various species (14,16,21,23), the cardioprotective effect of ischemic postconditioning was blunted in aged mice, hypercholesterolemic rabbits, and leptindeficient obese ob/ob mice (28). The study from our laboratory (28) also reported the inability of ischemic postconditioning to protect type 2 diabetic mice against I/R injury.…”

“…First, the potential clinical utilities and opportunities of pacing-induced postconditioning seem to be very promising, considering that at least four carefully designed clinical trials published from 2012 to 2014 on ischemic postconditioning have yielded disappointing negative results (11,12,16,26). Therefore, it is warranted to further investigate whether ventricular pacing as an alternative postconditioning modality that differs from the graded reperfusion afforded by ischemic postconditioning could provide better cardioprotection.…”