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Confirming the overall negative results of the randomized ACT trial, a new subanalysis looking specifically at patients with diabetes also shows no protective effect from N-acetylcysteine (NAC) given before and after angiography. The findings were published online April 9, 2013, ahead of print in Circulation: Cardiovascular Interventions.

The Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT), published in Circulation in August 2011, randomized 2,308 patients undergoing coronary or peripheral vascular angiography to NAC (1,200 mg twice daily) or placebo. The study found that the antioxidant did not reduce acute kidney injury (AKI), defined as 25% elevation in serum creatinine above baseline between 48 and 96 hours after angiography.

For the subanalysis, Otavio Berwanger, MD, PhD, of the Hospital do Coração (São Paulo, Brazil), and colleagues focused on 1,395 patients with diabetes in ACT. They found no differences between the treatment and control groups with regard to contrast-induced AKI (primary endpoint) or doubling of serum creatinine levels at 48 to 96 hours. Nor were there differences in cardiovascular death or the composite of death or need for dialysis within 30 days (table 1).

Table 1. Outcomes in Diabetic Patients Undergoing Angiography

Abbreviation: SCr, serum creatinine.

Among diabetic patients, the effect of NAC on AKI was unchanged by baseline glomerular filtration rate (RR 0.99; 95% CI 0.5-1.74 for ≤ 60 mL/kg per 1.73 m² and RR 0.96; 95% CI 0.72-1.28 for > 60 mL/kg per 1.73 m²; P value for homogeneity = 0.93).

Evidence Mounts Against NAC

According to the authors, the findings dovetail with previous randomized trials involving large numbers of diabetic patients as well as with observational studies showing no benefit from NAC in patients undergoing angiography.

The strengths of this analysis include its large size and randomized design, as well as the use of 1,200-mg NAC rather than previously tested 600 mg twice daily, Dr. Berwanger and colleagues observe.

However, the researchers acknowledge that use of serum creatinine as a marker of kidney damage could be considered a limitation. “Some recent publications suggest that newer markers such as cystatin C are more reliable for detecting contrast-induced acute kidney injury,” they write. “Nevertheless, results based on creatinine measures were consistent with those observed for other clinical end points.”

There is also the chance that the duration of NAC treatment—administered every 12 hours, 2 doses before and 2 after angiography—was not long enough to see an effect, the authors note. But extending treatment would likely not change results, they say, because renal dysfunction peaks soon before angiography and normalizes quickly after the procedure.

Time to Forgo NAC?

Peter A. McCullough, MD, MPH, of St. John Providence Health System (Warren, MI), told TCTMD in an e-mail communication that the results are unsurprising and fall in line with all previous research. However, he noted, the relatively low rates of AKI seen here suggests that, for an unknown reason, diabetic patients in ACT “had attenuated risk” compared with those in other trials.

Dr. Berwanger and colleagues conclude that NAC should not be used to prevent AKI in diabetic patients undergoing angiography. “These findings have important implications for clinical practice and may prevent unnecessary procedure delays and health expenditures associated with the administration of acetylcysteine,” they write.

 

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Source:
Berwanger O, Cavalcanti AB, Sousa AMG, et al. Acetylcysteine for the prevention of renal outcomes in patients with diabetes mellitus undergoing coronary and peripheral vascular angiography: A substudy of the Acetylcysteine for Contrast-Induced Nephropathy Trial. Circ Cardiovasc Interv. 2013;Epub ahead of print.

 

 

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