Ischemic Postconditioning Holds No Clinical Benefit for STEMI Patients
In addition to failing to improve myocardial reperfusion after primary PCI, ischemic postconditioning does not reduce major adverse events through 1 year, according to a secondary analysis of the POST trial published online February 28, 2015, ahead of print in the American Heart Journal.
The main results of the trial showed that adding the intervention to primary PCI did not increase the rate of complete ST-segment resolution 30 minutes after the procedure (primary endpoint) or reduce 30-day MACE. The 1-year outcomes, reported by Joo-Yong Hahn, MD, of Samsung Medical Center (Seoul, South Korea), and colleagues, were a prespecified secondary endpoint.
The POST trial included 700 STEMI patients (mean age 60 years; 77% male) who underwent primary PCI within 12 hours of the onset of chest pain and had TIMI flow grade 0 or 1 in the infarct-related artery and a target lesion located in a native coronary vessel with a diameter of 2.25 to 4.25 mm.
The patients were randomized between July 2009 and June 2012 to conventional primary PCI with or without ischemic postconditioning. Successfully performed per protocol in 323 patients (92.3%), postconditioning was initiated immediately after restoration of coronary blood flow. An angioplasty balloon positioned at the culprit lesion was inflated for 1 minute followed by 1 minute of deflation, for 4 cycles.
All patients received loading doses of aspirin and clopidogrel, with dual antiplatelet therapy recommended for at least 12 months. Baseline, angiographic, and procedural characteristics and medication use at discharge and 1 year were similar between groups, although clopidogrel use trended higher in the postconditioning group at 1 year (P = .053).
At 1 year, rates of the composite of death, MI, severe heart failure, or definite/probable stent thrombosis (primary endpoint) and its individual components did not differ between groups, with the numbers suggesting possible harm from postconditioning (table 1).
There also were no differences in rates of cardiac death and TVR. The overall findings were consistent in a per-protocol analysis and across subgroups.
Compared with patients who had partial or no ST-segment resolution, those with complete resolution had lower risks of MACE (HR 0.37; 95% CI 0.16-0.84) and death (HR 0.32; 95% CI 0.12-0.85) at 1 year, showing that “complete [ST-segment resolution] was relevant as the primary endpoint in the POST trial,” the authors write.
Lack of Benefit Might Be Explained by Adjunctive Therapies, Reflow Method
Both animal studies and smaller human trials have suggested that ischemic postconditioning reduces myocardial infarct size. The limited information on clinical outcomes came from smaller single-center studies.
“The number of enrolled patients and multicenter design were merits of our study in which the benefit of ischemic postconditioning regarding long-term clinical outcomes was not observed,” Dr. Hahn and colleagues write. Pointing to the hint of worse outcomes in the postconditioning group, they note that “several previous studies using cardiac magnetic resonance imaging reported harmful effects of ischemic postconditioning, supporting our results.”
According to the researchers, some aspects of the study design could explain why no benefit was observed.
“First of all, we allowed thrombus aspiration, predilation before stenting, or use of glycoprotein IIb/IIIa inhibitors [to be at] the operators’ discretion,” they write. “These adjunctive measures may mitigate [the] protective effect of ischemic postconditioning, which may reduce infarct size in selected [settings].”
Second, achieving reflow by using “thrombus aspiration or wire passage, withdrawal of an aspiration catheter, and insertion of an angioplasty balloon may result in delay between reflow and the first reocclusion,” they note. “In an animal study, delaying the postconditioning intervention decrease[d] the infarct size reduction and the first minute after reperfusion appear[d] to be critical to cardioprotection by ischemic postconditioning.”
Subgroup analyses did not support a difference in outcomes based on the method of obtaining reflow, however.
Although the authors acknowledge that the trial included too few patients to draw definitive conclusions about clinical outcomes, they say that the lack of effects on complete ST-segment resolution, myocardial blush, and postprocedural TIMI flow grade—“well-established surrogates for clinical outcomes”—make it unlikely that a larger trial would provide different results.
“Further studies are warranted to investigate other strategies, such as remote conditioning or pharmacologic conditioning, to prevent lethal reperfusion injury,” they write.
Hahn J-Y, Yu CW, Park HS, et al. Long-term effects of ischemic postconditioning on clinical outcomes: 1 year follow-up of the POST randomized trial. Am Heart J. 2015;Epub ahead of print.
- The study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare of the Republic of Korea.
- Dr. Hahn reports receiving research grants from the Korean Society of Interventional Cardiology and the Sungkyunkwan University Foundation for Corporate Collaboration and speaker’s fees from Abbott Vascular, AstraZeneca, Daiichi Sankyo, Eli Lilly, Pfizer, and Sanofi-Aventis.
- Postconditioning Ineffective in STEMI Patients Receiving Primary PCI
- Delayed Postconditioning Ineffective in STEMI Patients Undergoing Primary PCI
- Postconditioning Again Fails to Reduce Reperfusion Injury After STEMI