Could you explain the rationale and design behind the NACIAM trial?
The NACIAM trial, which stands for the N-acetylcysteine in Acute Myocardial Infarction trial, is a study investigating the potential benefits of N-acetylcysteine in both reperfusion injury as well as perfusion in patients with ST-elevation myocardial infarction.

The rational behind this is, as we all know ST-elevated myocardial infarction is associated with an acute coronary occlusion, for which we undertake reperfusion therapy. As a result of the promptness of the reperfusion therapy will result in an infarct size. But the dependent variables for the infarct size are the duration of ischaemia as well as reperfusion injury. So the duration of ischemia results in ischaemic injury due to free radical generation, as does the reperfusion injury.

The rational behind using N-acetylcysteine is that it is a free radical scavenger, and therefore reduces oxidative stress and also reperfusion injury. It also has a secondary effect in that it potentiates the effect of glyceryl trinitrate, or GTN.

And GTN has beneficial properties both in vasodilation, anti-platelet effects as well as reducing inflammation. So these benefits are enhanced with the use of N-acetylcysteine.

The purpose of the NACIEM study was to assess the efficacy of adding high-dose intravenous N-acetylcysteine to low-dose intravenous GNT in acute ST-elevation myocardial infarction patients undergoing primary percutaneous coronary interventions.

It was a randomised double-blind placebo-controlled multi-centre trial, and it involved patients who had a first time ST-elevation myocardial infarction within 12 hours of being randomized to either N-acetylcysteine or placebo with background GTN therapy.

It was a high-dose of NACIAN given in the first hour, and then continued at a low dose for the next 47 hours.

An MRI was performed was performed at about five days, the primary end point being the myocardial infarct size on MRI.

The secondary end point was myocardial salvage.

The key findings from this study was that there was a 5.5 per cent reduction in infarct size with the use of N-acetylcysteine compared with placebo. This is despite the fact that there was not any difference between the groups in terms of size of infarction.

Consequently, there was a significant improvement in myocardial salvage. The plot you can see [see video] looking at myocardial salvage demonstrates that the shorter ischaemic time results in a greater beneficial effect of the N-acetylcysteine.

To summarise, the main findings from the study is that the addition of N-acetylcysteine to low-dose intravenous GTN reduces infarct size, increases myocardial salvage and there is a larger effect with a shorter duration of ischaemia.

The implications of this study is that with a reduction in infarct size of about 5.5 per cent could potentially translate in a 20 per cent reduction in mortality based on previous studies.

From here the next point to move on to, is to undertake a study where we’re looking at clinical end points, rather than the surrogate end point of myocardial infarct size.