Early use of N-Acetylcysteine (NAC) with Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Reduces Myocardial Infarct Size (The NACIAM Trial)
Background—Contemporary ST-elevation myocardial infarction (STEMI) management involves primary percutaneous coronary intervention (PCI) with on-going studies focusing on infarct size reduction utilizing ancillary therapies. N-acetylcysteine (NAC) is an antioxidant with reactive oxygen species scavenging properties that also potentiates the effects of nitroglycerin (NTG) and thus represents a potentially beneficial ancillary therapy in primary PCI. The NACIAM (NAC In Acute Myocardial infarction) trial examined the effects of NAC on infarct size in STEMI patients undergoing PCI.
Methods—This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous high dose NAC (29g over 2 days) with background low-dose NTG (7.2mg over 2 days) on early cardiac magnetic resonance (CMR) imaging-assessed infarct size. Secondary endpoints included CMR-determined myocardial salvage and creatine kinase (CK) kinetics.
Results—Of 112 randomized STEMI patients, 75 (37 in NAC & 38 in Placebo) underwent early CMR imaging. Median duration of ischemia pre-treatment was 2.4 hours. With background NTG infusion administered to all patients, those randomized to NAC exhibited an absolute 5.5% reduction in CMR-assessed infarct size relative to placebo (median 11.0% vs 16.5%; p=0.02). Myocardial salvage was approximately doubled in the NAC group (60% [37, 79%]) compared to placebo (27% [14, 42%], p<0.01) and median CK areas under the curve were 22,000 IU.hours and 38,000 IU.hours in the NAC and placebo groups, respectively (p=0.08).
Conclusions—High dose intravenous NAC administered with low dose intravenous NTG is associated with reduced infarct size in STEMI patients undergoing PCI. A larger study is required to assess the impact of this therapy on clinical cardiac outcomes.
Clinical Trial Registration—Australian New Zealand Clinical Trials Registry URL: http://www.anzctr.org.au/ Unique identifier: 12610000280000
- ST-segment elevation myocardial infarction
- percutaneous coronary intervention
- ischemia reperfusion injury
- magnetic resonance imaging
- clinical trial
- Received January 26, 2017.
- Revision received June 4, 2017.
- Accepted June 8, 2017.