The addition of intravenous (IV) N-acetylcysteine (NAC) to IV glyceryl trinitrate (GTN) significantly reduced infarct size by approximately one third in patients undergoing percutaneous coronary intervention (PCI) after ST-segment elevation acute myocardial infarction (STEMI), according to Hot Line research.
"Timely and effective myocardial reperfusion by PCI is the treatment of choice for limiting myocardial infarct size and improving clinical outcomes in patients presenting with STEMI. However, additional pharmacological interventions may help to reduce infarct size further," noted Sivabaskari Pasupathy, PhD candidate, from the University of Adelaide, in Adelaide, Australia, who presented the findings at ESC Congress 2016.
"Any intervention that actually reduces myocardial infarct size by approximately a third might reasonably be expected to substantially improve long-term outcomes."
NACIAM (N-AcetylCysteine In Acute Myocardial infarction), a placebo-controlled, double-blind trial, included 112 STEMI patients (mean age 64 years) from 3 Australian hospitals.
All patients underwent emergency PCI and also received low dose intravenous GTN. They were randomized pre-PCI to receive either high dose (15 grams/24 hours) NAC or an identical placebo, both delivered intravenously over 48 hours, "with the hypothesis that NAC might reduce infarct size, either by potentiating the effects of GTN or via 'scavenging' of reactive oxygen species," said Dr. Pasupathy.
Cardiac magnetic resonance (CMR) imaging performed within one week (early) and again 3 months post MI (late) showed that patients who received NAC had reductions in infarct size of 33% and 50% respectively compared to placebo (p=0.02 for both).
There was a similar but not significant trend towards reduction in creatine kinase release.
Additionally, myocardial salvage, measured at one week, was approximately doubled in patients who received NAC (60% vs 27%, p<0.001), and there was also evidence of accelerated tissue reperfusion and hypochlorous acid "scavenging" in these patients.
Over 2 years of follow-up, the combination of cardiac readmissions and deaths was less frequent in NAC-treated (3 vs 16 patients, P<0.01).
Safety endpoints including hypotension, bleeding, and contrast-induced nephropathy were similar in both groups.
"Intravenous NAC administration was associated with more rapid chest pain resolution, improved myocardial salvage, a favourable in-hospital safety profile, sustained infarct size reduction at 3 months post-STEMI, and promising clinical outcomes at 2 years," concluded Dr. Pasupathy. "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," she noted.
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