Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

N-acetylcysteine prevented contrast-medium–induced nephropathy in primary angioplasty

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ACP J Club. 2006 Nov-Dec;145:63. doi:10.7326/ACPJC-2006-145-3-063


Clinical Impact Ratings

Hospitalists: 6 stars

Cardiology: 6 stars

Nephrology: 7 stars


Source Citation

Marenzi G, Assanelli E, Marana I, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med. 2006;354:2773-82. [PubMed ID: 16807414]


Abstract

Question

In patients having primary angioplasty, how effective is N-acetylcysteine (NAC) for preventing contrast-medium–induced nephropathy?

Methods

Design: Randomized placebo-controlled trial.

Allocation: Unclear allocation concealment.*

Blinding: Blinded (study investigators involved in the procedures).*

Follow-up period: Up to hospital discharge.

Setting: A coronary care unit in Centro Cardiologico Monzino, Milan, Italy.

Patients: 354 patients (mean age 62 y, 81% men) who received primary angioplasty for ST-elevation myocardial infarction within 12 hours (18 h for cardiogenic shock) after onset of symptoms. Exclusion criteria were long-term dialysis and allergy to NAC.

Intervention: Standard dose NAC (n= 116), high-dose NAC (n= 119), or placebo (n= 119). The standard-dose group received an intravenous (IV) bolus of NAC, 600 mg, before angioplasty plus a 600-mg tablet, orally twice daily for 48 hours after angioplasty. The high-dose group received a 1200-mg IV bolus and 1200 mg orally twice daily for 48 hours. All patients received IV isotonic saline, 0.9% at 1 mL/kg of body weight per hour (0.5 mL/kg per h for heart failure) for 12 hours.

Outcomes: Contrast-medium–induced nephropathy (≥ 25% increase from baseline in serum creatinine level within 72 h after angioplasty). Secondary outcomes included in-hospital mortality and the composite endpoint of death, acute renal failure requiring renal-replacement therapy, or need for mechanical ventilation.

Patient follow-up: 99.4%.

Main results

The standard- and high-dose NAC groups had lower incidences of contrast-medium–induced nephropathy and the composite endpoint than did the placebo group; the high-dose NAC group had a lower incidence of in-hospital mortality than did the placebo group (Table). Standard-dose NAC and placebo groups did not differ for in-hospital mortality (Table).

Conclusion

In patients having primary angioplasty, N-acetylcysteine reduced the incidence of contrast-medium–induced nephropathy.

*See Glossary.

Sources of funding: Centro Cardiologico Monzino and Italian Ministry of Health.

For correspondence: Dr. G. Marenzi, University of Milan, Milan, Italy. E-mail giancarlo.marenzi@ccfm.it.


Table. Standard-dose N-acetylcysteine (NAC) or high-dose NAC vs placebo in patients having primary angioplasty at 48 hours†

Outcomes Standard NAC High NAC Placebo RRR (95% CI) NNT (CI)
Contrast-medium–induced nephropathy‡ 15% 33% 55% (26 to 73) 6 (4 to 14)
8.5% 33% 74% (52 to 86) 5 (3 to 7)
In-hospital death 4.3% 11% 60% (−3.3% to 85) Not significant
2.5% 11% 77% (26 to 93) 12 (7 to 46)
Composite endpoint§ 7.0% (8/115) 18% (21/119) 61% (17 to 82) 10 (6 to 43)
5.1% (6/118) 18% (21/119) 71% (34 to 88) 8 (5 to 22)

†Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
‡Defined as ≥ 25% increase from baseline in serum creatinine level.
§Death (standard NAC vs high NAC vs placebo = 4.3% vs 2.5% vs 11%), acute renal failure requiring renal-replacement therapy (1.7% vs 0.9% vs 5.0%), or need for mechanical ventilation (0.9% vs 1.7% vs 1.7%).


Commentary

The study by Marenzi and colleagues examined the effects of NAC specifically in patients receiving primary angioplasty for acute myocardial infarction and compared efficacies of low- and high-dose NAC with a control group. Patients in the study received a higher dose of contrast medium than did those in previous studies (about 260 mL), and NAC reduced the incidence of contrast nephropathy regardless of baseline renal or left-ventricular function.

Despite results from ≥ 22 randomized trials and 12 meta-analyses, the effectiveness of NAC has remained controversial. Previous studies were limited because they relied on a surrogate endpoint (i.e., change in serum creatinine level). While this surrogate endpoint is associated with greater patient morbidity and mortality, a beneficial effect of NAC on clinical endpoints has never been shown. The observations of Marenzi and colleagues showing lower mortality and a lower composite endpoint of death, dialysis, or mechanical ventilation in NAC-treated patients are of great interest. However, these findings should be interpreted with caution. The placebo group had more frequent events than expected, and such dramatic clinical benefit has not been previously observed in high-risk patients (1). Differences might be attributed to chance alone. The lack of blinding of patients, clinicians, and outcome assessors, and the fact that these clinical events were not prespecified, may introduce bias.

Nevertheless, in light of its potential clinical benefit, safety, and low cost, prophylactic NAC should be considered for high-risk patients receiving intraarterial contrast in addition to appropriate hydration and judicious use of a low or isoosmolar contrast agent (1). High-dose NAC (IV or oral) may be more effective in preventing contrast nephropathy when the administration of large doses of contrast medium (> 140 mL) is anticipated (2). A larger multicenter clinical trial is needed to confirm whether high- or low-dose NAC reduces the incidence of clinical endpoints.

Matthew James, MD
Braden Manns, MD
University of Calgary
Calgary, Alberta, Canada


References

1. Pannu N, Wiebe N, Tonelli M. Prophylaxis strategies for contrast-induced nephropathy. JAMA. 2006;295:2765-79. [PubMed ID: 16788132]

2. Briguori C, Colombo A, Violante A, et al. Standard vs double dose of N-acetylcysteine to prevent contrast agent associated nephrotoxicity. Eur Heart J. 2004;25:206-11. [PubMed ID: 14972420]