N-acetylcysteine reduces infarct size

An inexpensive drug delivered promptly to patients with ST-elevated myocardial infarction (STEMI) reduces infarct size by about a third compared to standard treatment with PCI alone, cardiologists in Adelaide have found.

Results from the NACIAM trial involving 112 STEMI patients showed that the addition of IV N-acetylcysteine (NAC) to low dose glyceryl trinitrate (GTN) given to STEMI patients undergoing PCI resulted in reductions in infarct size of 33% and 50%, respectively, compared with placebo at five days and three months respectively.

NAC was also associated with faster chest-pain resolution and improved myocardial salvage despite the fact that there was no difference between the intervention and control groups in terms of size of infarction.

Speaking to the limbic lead author Dr Sivabaskari Pasupathy from the University of Adelaide said: “The key finding from this study was that NAC was associated with a 5.5% reduction in infarct size so, compared to placebo, that’s a 30% reduction. Studies have shown if there is a 5% reduction in infarct size that can reduce the chance of death or a second infarct by 20% – that’s a substantial long-term benefit.”

She said doctors at Adelaide’s Queen Elizabeth hospital first became interested in using NAC for STEMI after they found it reduced the risk of MI in patients with stable angina.

The hypothesis for the drugs effectiveness in STEMI centered around the fact that it was a free radical scavenger that might reduce infarct size either by potentiating the effects of GTN or via scavenging of reactive oxygen species.

Over two years of follow-up, the combination of cardiac readmissions and deaths was less frequent in NAC-treated patients (three vs 16 patients) Dr Pasupathy said, adding that most benefit occurred in patients treated early.

“That’s a key point – we started the drug as soon as possible, the moment the patient comes in through the door, if they had a ST elevation on ECG we started them on the drug combination straight away so at least most of the time it was given at least 40 minutes before the angiogram was performed.”

She added that more patients in the NAC arm had an open artery at angiography, suggesting that NAC may aid reperfusion as well as reduce reperfusion injury.

Dr Pasupathy also noted that while infarct size was reduced in the intervention arm there seemed to be no significant improvement in LV function.

“That was surprising…we were expecting to see improvement in LV function but we didn’t see that and that’s probably because of improved medical management at the moment – most of the patients were already on medication to improve LV function – and I guess you can’t improve on something that’s already being optimally treated.”

While there were no adverse events observed in the study Dr Pasupathy said hypotension with GTN may be concern but a larger outcomes study would be needed to assess that and other questions raised about how the drugs work to reduce infarct size.

Dr Pasupathy is currently recruiting hospitals to be involved in a larger study.

Patients in the trial all received GTN and were randomised to receive either 15 g/24 hours of  NAC or placebo, within 12 hours of symptom onset. Both drugs were started in the emergency department and given intravenously over 48 hours.

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