Milan, Italy - N-acetylcysteine appears to prevent contrast-medium-induced nephropathy in acute myocardial infarction patients undergoing primary angioplasty, a new prospective randomized study shows [1].

Dr Giancarlo Marenzi (University of Milan, Italy) and colleagues report their findings in the June 29, 2006 issue of the New England Journal of Medicine.

"This is the first study to evaluate the prophylactic effect of N-acetylcysteine in patients with acute MI undergoing primary PCI," senior author Dr Antonio L Bartorelli told heartwire. "We were surprised by the positive effect. It's a new application for an old drug."

They also found evidence that use of the drug reduced long-term morbidity and mortality, but this will require confirmation, he added.

Bartorelli explained that contrast-medium-induced nephropathy is a recognized complication of interventional procedures and is associated with prolonged hospitalization and adverse outcomes. Overall, the incidence of this complication is low, but in those who already have preexisting renal insufficiency it is much higher.

"This is a very critical complication," he adds, "and there are many epidemiological data showing that the prognosis for people with contrast-medium-induced nephropathy is bad."

In elective procedures, patients with renal insufficiency can be screened out—or treated with prophylactic measures such as hydration and hemofiltration—he adds, but for emergency PCI for acute myocardial infarction there is no time to check their renal function beforehand. Also, acute MI is "hard to treat, patients are often dehydrated from profound sweating, they have hemodynamic instability, and in complicated cases we can use a large amount of contrast medium," he explains.

Previous studies with N-acetylcysteine to prevent contrast-medium-induced nephropathy during elective procedures "have produced conflicting results," he notes, and no conclusive data on morbidity and mortality following N-acetylcysteine have been reported.

In this new trial, the researchers randomly assigned 354 consecutive patients undergoing primary angioplasty for acute myocardial infarction to one of three groups: standard dose of N-acetylcysteine (a 600-mg IV bolus dose before PCI and 600 mg orally twice daily for the 48 hours after angioplasty); double dose (1200-mg IV bolus followed by 1200 mg orally twice daily for 48 hours); or placebo. All the patients also received hydration with isotonic saline for 12 hours after the intervention.

Contrast-medium-induced nephropathy occurred in a third of the control patients compared with 15% and 8% of the standard- and double-dose N-acetylcysteine patients, respectively.

We are now using this double dose as our standard of care in all acute MI patients undergoing emergency PCI.

Two other recent trials have suggested that there is a dose-dependent effect of N-acetylcysteine, Bartorelli says, and "we showed a similar outcome. The effects were even more pronounced with a double dose."

"This is a very convenient drug to use," he adds. "It's very easy to give the initial IV bolus dose and then you just follow this up with two oral doses. And it's very cheap. We are now using this double dose as our standard of care in all acute-MI patients undergoing emergency PCI."

Although the study was not powered to assess differences in morbidity and mortality, patients treated with N-acetylcysteine had significantly better in-hospital outcomes, the researchers note.

But the mechanisms underlying this improvement—which are thought to include a protective, antioxidant effect on both the kidneys and the heart—have not been completely elucidated, they stress.

"Although our findings are promising, further data are needed before any conclusions can be made," they state.