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Atlanta, GA - New studies presented here suggest that acetylcysteine (Mucomyst®), an antioxidant, may prevent chronic renal insufficiency related to the use of contrast media in patients undergoing both diagnostic angiography and PCI. A third study showed that among patients at greatest risk for renal problems, hemofiltration during interventional procedures using contrast may significantly reduce these complications. The studies were presented here at the American College of Cardiology 51st Annual Scientific Session.
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Acetylcysteine in angiography and PCI
Two other studies presented here investigated one strategy to prevent CIN, oral pretreatment with acetylcysteine, an antioxidant agent.
In one, acetylcysteine was studied in patients with renal dysfunction undergoing diagnostic coronary angiography. Acetylcysteine is actually now in routine use in many cath labs since publication of a paper in 1997 by Tepel et al in the New England Journal of Medicine,1 said Dr Elie N Mouhayar (Geisinger Medical Center, Pennsylvania, PA). The paper showed a benefit from its use in patients undergoing contrast-enhanced CT, he told heartwire in an interview here. Since then, the benefit seen in that study has been extrapolated to coronary angiography and interventional procedures, where significantly more contrast is used, he said. Earlier this year, a randomized study of acetylcysteine was published by researchers at Tufts University, Boston, showing a benefit from treatment in patients undergoing angiography.2
In this study, researchers randomized 55 consecutive patients with baseline serum creatinine of 1.2 mg/dL to receive either standard hydration therapy - a proven strategy to reduce CIN - or hydration therapy plus 600 mg of acetylcysteine given orally in 4 doses.
CIN was defined as an increase in creatinine of 25% from baseline or an increase of 0.5 mg/dL. They found significant reductions in both serum creatinine elevation and the incidence of CIN with acetylcysteine treatment.
CIN by baseline serum creatinine level, acetylcysteine versus placebo|
Baseline serum creatinine level |
Acetylcysteine + hydration |
Hydration alone |
p value |
|
Baseline SC > 1.2 | 3 (5%) | 9 (16%) | 0.02 |
|
Baseline SC > 2.0 | 1 (5%) | 6 (66%) | <0.001 |
"So this is the major benefit from acetylcysteine; we think it has a protective effect," Mouhayar said.
Contrast dye is thought to negatively affect the kidney by the induction of renal medullary ischemia by vasoconstriction, and more directly, by increasing the production of oxygen free radicals. While the precise mechanism of protection is not known, acetylcysteine has a vasodilatory effect which may protect the medulla, Mouhayar said, as well as antioxidant effects.
In the second study, researchers from the Lenox Hill Heart and Vascular Institute examined the utility of acetylcysteine in preventing CIN among patients with chronic renal insufficiency, defined as baseline serum creatinine > 1.5 mg/dL, undergoing PCI.
Procedural and in-hospital outcomes were compared in 57 patients randomized to 600 mg bid of acetylcysteine plus hydration, or hydration therapy alone. The researchers, with first author Dr Milena G Adamian, found those treated with acetylcysteine were significantly less likely to have CIN or require dialysis after their PCI procedure.
Contrast-induced nephropathy and dialysis|
Treatment |
Acetylcysteine + hydration |
Hydration alone |
p value |
|
CIN | 5.7% | 34.7% | 0.009 |
|
In-hospital dialysis | 2.9% | 17.4% | 0.06 |
"Mucomyst (acetylcysteine) administration prior to PCI in chronic renal insufficiency patients has protective effect on renal function," the researchers conclude. "Randomized, prospective trials are required to determine the validity of these findings."
Hemofiltration
A more aggressive intervention to prevent CIN was undertaken by Italian researchers, with encouraging results. Dr Ivana Marana (Institute of Cardiology, University of Milan, Italy) and colleagues used continuous venovenous hemofiltration (CVVH) in patients at greatest risk for renal dysfunction from the use of contrast agents during PCI, those with pre-existing renal failure.
This technique offers a variety of potential advantages over the use of hydration alone, Marana told heartwire in an interview here. It allows the use of very high saline volumes to increase renal flow - while normal hydration is 1 mL/kg/hour, they routinely use about 1000 mL/hour, she said. The filter also removes excess contrast agent, reducing the exposure of the kidneys.
In the study presented here, the researchers compared CVVH 10 hours prior to and 10 hours after the procedure to standard hydration therapy 24 hours before and after the procedure in 54 patients with renal failure (serum creatinine >2 mg/dL) undergoing PCI. Diabetic patients made up about 30% of each group.
The researchers found positive effects on serum creatinine and other indicators of renal function with the hemofiltration procedure, Marana said. For example, after PCI, serum creatinine increased (<0.5 mg/dL) in 61% of the hydration patients, but none of those in the CVVH group.
Both in-hospital mortality and the need for temporary and permanent hemodialysis were significantly higher in the group receiving hydration therapy alone.
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Indicator |
CVVH |
Hydration |
|
In-hospital mortality | 2.4% | 14.7%* |
|
Temporary hemodialysis | 0% | 39% |
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Permanent hemodialysis | 0% | 6% |
The only potential problem Marana did note was the cost: The filters alone required for this procedure cost about $200. However, given the lower incidence of all the other complications, it may still be cost-effective, she concluded.
