ESC 2016: Adding N-acetylcysteine to glyceryl trinitrate reduces infarct size by a third

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ESC Picto 2016_feature

A placebo-controlled, double-blind trial—NACIAM (N-acetylcysteine in acute myocardial infarction)—indicates that adding intravenous N-acetylcysteine to intravenous glyceryl trinitrate significantly reduced infarct size by approximately one third in patients undergoing percutaneous coronary intervention (PCI) after ST-segment elevation acute myocardial infarction (STEMI).

Presenting the study at the 2016 European Society of Cardiology (ESC) congress (27–31 August, Rome, Italy), Sivabaskari Pasupathy (University of Adelaide, Adelaide, Australia) reported that 112 STEMI patients undergoing emergency PCI were randomised (prior to the procedure) receive either high dose (15 grams/24 hours) N-acetylcysteine or an identical placebo—both delivered intravenously over 48 hours. All patients received low-dose intravenous glyceryl trinitrate. She commented that the hypothesis of the study was “the hypothesis that N-acetylcysteine might reduce infarct size, either by potentiating the effects of GTN or via ‘scavenging’ of reactive oxygen species”.

N-acetylcysteine was associated with significant reductions in infarct size compared with placebo (as observed with cardiac magnetic resonance imaging, MRI): 33% at one week and 50% at three months (p=0.02 for both comparisons). Additionally, myocardial salvage, measured at one week after the PCI, was approximately doubled in patients who received N-acetylcysteine (60% vs. 27%; p<0.001). There was also evidence of accelerated tissue reperfusion and hypochlorous acid “scavenging” in these patients. Furthermore, there was a similar—but not significant trend—towards reduction in creatine kinase release with N-acetylcysteine.

Over two years of follow-up, the combination of cardiac readmissions and deaths was less frequent in N-acetylcysteine-treated patients (3 vs. 16 for placebo patients; p<0.01).  Safety endpoints, including hypotension, bleeding, and contrast-induced nephropathy, were similar in both groups.

Pasupathy commented: “Intravenous N-acetylcysteine administration was associated with more rapid chest pain resolution, improved myocardial salvage, a favourable in-hospital safety profile, sustained infarct size reduction at three months post-STEMI, and promising clinical outcomes at two years. While the results of this study are encouraging, we would prefer to regard NACIAM as the precursor of a follow-up study, sized for clinical end-points.”