Letter by Mansour et al Regarding Article, “Early Use of N-Acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-Acetylcysteine in Acute Myocardial Infarction])”

To the Editor:

We read with great interest the article by Pasupathy et al¹ reporting the beneficial role of the early administration of intravenous N-acetylcysteine with low-dose intravenous nitroglycerin in patients with acute ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention.

N-Acetylcysteine (NAC), by disrupting the disulfide bond in the von Willebrand Factor A1 domain, can induce arterial thrombolysis through the reduction of large von Willebrand Factor multimers.^2,3 It is important to note that this thrombolytic effect might be limited to high–shear-stress zones, which is conceptually appealing to reduce the risk of systemic bleeding when used in patients with ST-segment–elevation myocardial infarction.

In vitro, this structural effect on the von Willebrand Factor is only seen at concentrations >4 mmol/L.^2,3

A pharmacokinetic study of intravenous NAC during acetaminophen overdose showed that the mean maximum plasma concentration after a 150 mg/kg NAC bolus over 15 minutes was 554 mg/L (3.4 mmol/L).⁴

Pasupathy and colleagues administered intravenous NAC at 20 mg/min during the first hour, followed by 10 mg/min for 47 hours.¹ With the use of this regimen, the plasma concentration of NAC should not exceed 4 mmol/L in the first hours of treatment.

It seems therefore unlikely that the beneficial effects of NAC demonstrated in the NACIAM trial (N-Acetylcysteine in Acute Myocardial Infarction) are related to its thrombolytic properties.

Further research is needed to assess the thrombolytic effect of high intravenous concentrations of NAC on coronary artery thrombosis.