N-Acetylcysteine for Myocardial Salvage in STEMI? NACIAM Trial Treads Where Many Have Flopped Before

A small study out of Australia is using some old agents in a new setting and seeing some promising—albeit preliminary—results.

According to Sivabaskari Pasupathy (University of Adelaide, Australia), who presented the study during a Hotline session at the European Society of Cardiology Congress 2016 today, early N-acetylcysteine (NAC) infusion on top of glyceryl trinitrate (GTN) appears to reduce infarct size and increase myocardial salvage in STEMI patients.

The NACIAM pilot trial is the latest in a long string of neutral studies that have studied a range of compounds with the hope of reducing reperfusion injury and protecting the myocardium in acute MI. N-acetylcysteine is more commonly used with to prevent contrast nephropathy although even here, support for its protective powers are mixed.

For NACIAM, Pasupathy, with senior author John Beltrame, MD (University of Adelaide), and colleagues, randomized 75 patients to NAC plus GTN, both delivered by infusion, or to GTN infusion coupled with placebo. The NAC protocol involved an infusion of 20 mg/min for 1 hour, followed by 10 mg/min for the next 47 hours. GTN dose in both arms was 2.5 µg/min for the 48-hour period. 

On day 5, MRI showed that infarct size was significantly greater in the placebo/GTN group than with NAC/GTN alone (16.5% versus 11%, P < 0.05), while myocardial salvage was significantly less (27% vs 60%, (P < 0.05). Total ischemic time was significantly lower in the NAC/GTN-treated patients. 

Beyond the Boneyard?

During a morning press conference Beltrame acknowledged that the clinical efficacy of this approach remains to be established, particularly given the failure of other drugs in this arena, most recently the CIRCUS study of cyclosporine. There are a couple key differences between the strategy used in CIRCUS versus in the current study, he noted. For one, NAC is given in the emergency room at the time of presentation. It is also given in combination with GTN, potentially potentiating the ability of the latter drug to improve reperfusion. 

 “The key thing now is that we need to take this on to a clinical outcomes study,” Beltrame said.

Nevertheless, he added, their hospital is already using the drug routinely in STEMI patients, on the grounds that it is safe and at least in preliminary imaging studies appears to be helping.

Session moderator Jorge Belardi, MD (Instituto Cardiovascular de Buenos Aires, Argentina), found no fault with this approach, commenting, “This is a very benign combination. . . . Why not do it?” Indeed, he added, many centers are already using NAC to prevent contrast injury.

Commenting on the study for TCTMD, however, Robert Harrington, MD (Stanford University, Stanford, CA), called the field of pharmaceutical interventions for reperfusion injury “a graveyard” of failed studies.

“There have been a lot of things that people have hypothesized to have worked that have been studied in animal models where they’ve reduced infarct size, either in the heart or in the brain, and the biology of a lot of these drugs has suggested they are going to work,” he said. “And then they’ve been applied in the human situation, for ST-elevation MI or coronary bypass surgery to attenuate complications of cardiopulmonary bypass, and in none of these areas have they actually been shown to improve outcomes. So it’s an important area, maybe eventually we’ll get it right [and] maybe this is the one, but that’s going to require clinical confirmation in outcome studies.”

Source:

• Pasupathy S, Tavella R, Grover S, et al. The early use of N-acetylcysteine (NAC) with Glyceryl Trinitrate (GTN) in STEMI NACIAM Trial: A pilot study. Presented at: European Society of Cardiology Congress 2016. August 27, 2016. Rome, Italy..

Disclosures: 

• Pasupathy reports having no conflicts.

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