Benefit of Acetylcysteine for Prevention of Contrast-Induced Nephropathy
Benefit of Acetylcysteine for Prevention of Contrast-Induced Nephropathy
Primary angioplasty for acute myocardial infarction (AMI) is associated with a higher rate of radiocontrast-induced nephropathy (RCIN) than elective intervention.
To establish whether acetylcysteine can prevent RCIN in patients with AMI undergoing primary angioplasty.
Screening for this prospective, randomized study took place from February 2003 to May 2005 in the coronary care unit of the Monzino Cardiology Centre, Milan, Italy. Consecutive patients with ST-segment elevation AMI who were undergoing primary angioplasty were eligible to enroll if they had presented ≤12 h after the beginning of symptoms. Those on chronic dialysis were excluded.
On a 1:1:1 basis, participants were randomized to receive 3,000 mg acetylcysteine (600 mg intravenously before angioplasty and 600 mg orally twice daily for 2 days after angioplasty), 6,000 mg acetylcysteine (1,200 mg intravenously before angioplasty and 1,200 mg orally twice daily for 2 days after angioplasty), or placebo. Heparin was administered during angioplasty, and all patients were given bare-metal stents. The non-ionic, low-osmolality contrast medium iohexol was used in all cases. After angioplasty, intravenous isotonic saline 0.9% was infused in all patients at 1 ml/kg/h for 12 h. Serum creatinine level was recorded on admission, daily for the following 3 days, and at discharge.
RCIN (≥25% increase in baseline serum creatinine level within 72 h of intervention) was the primary outcome measure.
At baseline, there were no significant differences in mean age, glomerular filtration rate (as estimated by the Cockroft-Gault equation), size of infarction, or volume of contrast used between the three treatment groups. RCIN occurred in 66/352 patients (19%) overall: 17/115 (15%) who received standard-dose (3,000 mg) acetylcysteine; 10/118 (8%) who received high-dose (6,000 mg) acetylcysteine; and 39/119 (33%) who were given placebo (P < 0.001). Multivariate logistic regression, with adjustment for factors including age, baseline serum creatinine level and contrast volume, revealed that placebo was associated with a significantly higher risk of RCIN than standard-dose acetylcysteine (odds ratio 2.60; 95% CI 1.30-5.18; P = 0.007) or high-dose acetylcysteine (odds ratio 5.78; 95% CI 2.56-13.16; P < 0.001). In-hospital mortality rate was significantly higher among patients on placebo (11%) than among patients who received standard-dose acetylcysteine (4%) or high-dose acetylcysteine (3%; P = 0.02). Patients on placebo also showed a significantly higher incidence of a composite endpoint comprising death, acute renal failure, or need for mechanical ventilation (18%) than those in the standard-dose or high-dose acetylcysteine groups (7% and 5%, respectively; P = 0.002). One patient who received standard-dose acetylcysteine developed a temporary rash that was considered likely to be acetylcysteine-related.
Acetylcysteine reduces the risk of RCIN in patients with AMI who are undergoing primary angioplasty, in an apparently dose-dependent manner.
Primary angioplasty for acute myocardial infarction (AMI) is associated with a higher rate of radiocontrast-induced nephropathy (RCIN) than elective intervention.
To establish whether acetylcysteine can prevent RCIN in patients with AMI undergoing primary angioplasty.
Screening for this prospective, randomized study took place from February 2003 to May 2005 in the coronary care unit of the Monzino Cardiology Centre, Milan, Italy. Consecutive patients with ST-segment elevation AMI who were undergoing primary angioplasty were eligible to enroll if they had presented ≤12 h after the beginning of symptoms. Those on chronic dialysis were excluded.
On a 1:1:1 basis, participants were randomized to receive 3,000 mg acetylcysteine (600 mg intravenously before angioplasty and 600 mg orally twice daily for 2 days after angioplasty), 6,000 mg acetylcysteine (1,200 mg intravenously before angioplasty and 1,200 mg orally twice daily for 2 days after angioplasty), or placebo. Heparin was administered during angioplasty, and all patients were given bare-metal stents. The non-ionic, low-osmolality contrast medium iohexol was used in all cases. After angioplasty, intravenous isotonic saline 0.9% was infused in all patients at 1 ml/kg/h for 12 h. Serum creatinine level was recorded on admission, daily for the following 3 days, and at discharge.
RCIN (≥25% increase in baseline serum creatinine level within 72 h of intervention) was the primary outcome measure.
At baseline, there were no significant differences in mean age, glomerular filtration rate (as estimated by the Cockroft-Gault equation), size of infarction, or volume of contrast used between the three treatment groups. RCIN occurred in 66/352 patients (19%) overall: 17/115 (15%) who received standard-dose (3,000 mg) acetylcysteine; 10/118 (8%) who received high-dose (6,000 mg) acetylcysteine; and 39/119 (33%) who were given placebo (P < 0.001). Multivariate logistic regression, with adjustment for factors including age, baseline serum creatinine level and contrast volume, revealed that placebo was associated with a significantly higher risk of RCIN than standard-dose acetylcysteine (odds ratio 2.60; 95% CI 1.30-5.18; P = 0.007) or high-dose acetylcysteine (odds ratio 5.78; 95% CI 2.56-13.16; P < 0.001). In-hospital mortality rate was significantly higher among patients on placebo (11%) than among patients who received standard-dose acetylcysteine (4%) or high-dose acetylcysteine (3%; P = 0.02). Patients on placebo also showed a significantly higher incidence of a composite endpoint comprising death, acute renal failure, or need for mechanical ventilation (18%) than those in the standard-dose or high-dose acetylcysteine groups (7% and 5%, respectively; P = 0.002). One patient who received standard-dose acetylcysteine developed a temporary rash that was considered likely to be acetylcysteine-related.
Acetylcysteine reduces the risk of RCIN in patients with AMI who are undergoing primary angioplasty, in an apparently dose-dependent manner.
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