It is unclear whether N-acetylcysteine is useful in preventing contrast-induced nephropathy in patients undergoing coronary angiography. Because of different inclusion and exclusion criteria and different definitions of studied parameters, various studies have reported different outcomes. A systematic search was done using PubMed, Ovid, and the Cochrane library, and studies were pooled after strict inclusion and exclusion criteria. Separate analysis was conducted for all endpoints including only studies that used an N-acetylcysteine (NAC) dose of 600 mg, and another separate analysis was conducted for all endpoints including only studies that used oral route NAC to study how the dose and route of administration of NAC affect the outcomes. The results of the pooled analysis significantly favored the use of NAC to prevent contrast-induced nephropathy in patients undergoing coronary angiography but failed to show any significant benefit in terms of creatinine levels preangiography and postangiography, need for dialysis, and all-cause mortality. The effects of route and dose of NAC did not show any significant difference except in respect to incidence of postcatheterization nephropathy. This study shows that NAC may not have any impact on clinical outcomes after peripheral or coronary artery catheterization and that dose and route do not seem to have any effect on these outcomes.
OBJECTIVE: To evaluate the comparative effectiveness of interventions (intravenous [IV] fluids, N-acetylcysteine, sodium bicarbonate, and statins, among others) to reduce the risk of contrast-induced nephropathy (CIN), need for renal replacement therapy, mortality, cardiac complications, prolonged length of stay, and other adverse events after receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media (IOCM).
DATA SOURCES: We searched for original published studies in MEDLINE(®), Embase(®), and the Cochrane Library through July 8, 2015. We also searched ClinicalTrials.gov and the Scopus database.
METHODS: Two reviewers independently reviewed each article for eligibility. For each study, one reviewer extracted the data and a second reviewer verified the accuracy. Both reviewers assessed study quality. Together, the reviewers graded the strength of evidence (SOE) on preventing CIN and other adverse outcomes for the comparisons of interest. The team quantitatively pooled results of studies that were sufficiently similar using a random-effects model. We considered a 25-percent relative risk difference to be clinically important.
RESULTS: We found 163 randomized controlled trials (RCTs) and 23 prospective studies of interventions to prevent CIN, including 67 RCTs comparing N-acetylcysteine with IV saline versus IV saline with or without a placebo; 28 RCTs comparing IV sodium bicarbonate versus IV saline; 7 RCTs comparing IV sodium bicarbonate versus N-acetylcysteine plus IV saline; 8 RCTs comparing a statin versus IV saline; 5 RCTs comparing a statin plus N-acetylcysteine versus N-acetylcysteine; 6 RCTs comparing statin versus statin, statin by dose, or statins plus other agents; 5 RCTs comparing an adenosine antagonist versus IV saline; 6 RCTs investigating hemodialysis or hemofiltration versus IV saline; 6 RCTs comparing ascorbic acid versus IV saline, and 3 RCTs comparing ascorbic acid to N-acetylcysteine. Although we found many studies investigating other interventions, the studies were too small and too few to support conclusions regarding the comparative effectiveness of those interventions. The studies were published between 1998 and 2015. The SOE was low that high-dose [>1,200 mg/day] N-acetylcysteine had a small clinically unimportant effect in preventing CIN when compared with IV saline (pooled risk ratio [RR], 0.78; 95% confidence interval [CI], 0.59 to 1.03); and the SOE was low that low-dose [≤1,200 mg/day] N-acetylcysteine had a borderline clinically important effect in preventing CIN when compared with IV saline (RR, 0.75; 95% CI, 0.63 to 0.89). A sensitivity analysis suggests the effect was clinically important when N-acetylcysteine was given for LOCM (moderate SOE; RR, 0.69; 95% CI, 0.58 to 0.84), but not when it was given for IOCM (low SOE; RR, 1.12; 95% CI, 0.74 to 1.69). Another sensitivity analysis found that the RR estimates did not differ between IV and intra-arterial routes of administration of contrast media. The SOE was low that using a statin plus N-acetylcysteine was more effective than N-acetylcysteine alone in preventing CIN in patients receiving intra-arterial contrast media (RR, 0.52; 95% CI, 0.29 to 0.93), and the SOE was low for a clinically important difference that was not statistically significant when comparing a statin plus IV saline to IV saline alone (RR, 0.68; 95% CI, 0.39 to 1.20). The SOE was low that IV sodium bicarbonate did not differ from IV saline in the risk of CIN (RR, 0.93; 95% CI, 0.68 to 1.27). The SOE was low for a clinically important reduction in CIN that was not statistically significant when comparing IV sodium bicarbonate with IV saline in patients receiving LOCM (RR, 0.65; 95% CI, 0.33 to 1.25). The SOE was low for a clinically important reduction in CIN that was not statistically significant when comparing ascorbic acid with IV saline (RR, 0.72; 95% CI, 0.48 to 1.01). The SOE was low that use of hemodialysis versus IV saline to prevent CIN did not reduce the risk of CIN and may even be harmful (RR, 1.50; 95% CI, 0.56 to 4.04).
CONCLUSIONS: The evidence shows a clinically important and statistically significant benefit in studies of three comparisons: low-dose N-acetylcysteine compared with IV saline, N-acetylcysteine compared with IV saline in patients receiving LOCM, and statins plus N-acetylcysteine compared with N-acetylcysteine alone in patients receiving intra-arterial contrast media. Future research is needed to determine whether statins can reduce CIN in patients receiving IV contrast media, and to further define specific contexts in which patients could benefit from use of N-acetylcysteine.
BACKGROUND: There have been a myriad of studies investigating the effectiveness of N-acetylcysteine (NAC) in the prevention of contrast induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) with or without percutaneous coronary intervention (PCI). However the consensus is still out about the effectiveness of NAC pre-treatment due to vastly mixed results amongst the literature.
OBJECTIVES: The aim of this study was to conduct a meta-analysis and trial sequential analysis to determine the effects of pre-operative NAC in lowering the incidence of CIN in patients undergoing CAG and/or PCI.
METHODS: A systematic literature search was performed to include all randomized controlled trials (RCTs) comparing NAC versus control as pretreatment for CAG and/or PCI. A traditional meta-analysis and several subgroup analyses were conducted using traditional meta-analysis with relative risk (RR), trial sequential analysis, and meta-regression analysis.
RESULTS: 43 RCTs met our inclusion criteria giving a total of 3277 patients in both control and treatment arms. There was a significant reduction in the risk of CIN in the NAC treated group compared to control (OR 0.666; 95% CI, 0.532-0.834; I2=40.11%; p=0.004). Trial sequential analysis, using a relative risk reduction threshold of 15%, indicates that the evidence is firm.
CONCLUSIONS: The results of the present paper support the use of NAC in the prevention of CIN in patients undergoing CAG±PCI. Future studies should focus on the benefits of NAC amongst subgroups of high-risk patients.
PURPOSE: To identify benefit of N-acetylcysteine (NAC) on patients with pre-existing renal insufficiency or diabetes.
BACKGROUND: NAC administration is a common method for prevention of contrast-induced nephropathy (CIN). Nevertheless, its benefit on patients with pre-existing renal insufficiency or diabetes remains uncertain and controversial.
METHODS: Randomized controlled trials (RCTs) to evaluate the efficacy of NAC for the prevention of CIN in patients with pre-existing renal insufficiency or diabetes were searched from the databases of MEDLINE, EMBASE, and Cochrane library. Pooled odds ratio (OR) with 95% confidence interval (95% CI) were calculated using fixed-effects model by the Mantel-Haenszel test.
RESULTS: Twenty RCTs involving 3466 subjects (1756 assigned to NAC and 1710 assigned to the control) were included in the pre-existing renal dysfunction group. Pooled analysis suggested a significant reduction in CIN among this group (OR, 0.76; 95% CI, 0.61-0.93; p = 0.008). However, the nine trials comparing NAC versus control among patients with diabetes (NAC, 367 subjects; control, 358 subjects) showed no benefit of NAC for prevention of CIN (OR = 0.87; 95% CI, 0.58-1.30; p = 0.50). No significant heterogeneity was detected (p = 0.07; I(2) = 34% for the group of pre-existing renal dysfunction; p = 0.40; I(2) = 5% for the group of diabetes).
CONCLUSION: Our results suggest that NAC decreases the incidence of contrast-induced nephropathy among patients with pre-existing renal insufficiency. The benefit was not existed in patients with diabetes.
BACKGROUND: N-Acetylcysteine (NAC) is reported to have potential for preventing of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography. However, the effectiveness of NAC in preventing CIN in patients undergoing contrast-enhanced computed tomography (CT) is still controversial. We conducted a meta-analysis of relevant randomized controlled trials (RCTs) to further examine this issue.
METHODS: RCTs were identified by computerized searching in PubMed, EMBASE, SCOPUS, and Cochrane databases. Two reviewers independently assessed the methodological quality of each study. A meta-analysis was performed to evaluate the effectiveness of NAC in preventing CIN in patients undergoing CT. The primary outcome was the incidence of contrast-induced nephropathy, and the requirement for dialysis. The secondary outcome was the change of serum creatinine.
RESULTS: Six randomized controlled trials were identified with a total of 496 patients meeting the criteria for this study. Prophylactic administration of NAC in patients with serum creatinine above 1.2 mg/dL undergoing contrast-enhanced CT, along with hydration, reduced the risk of CIN (relative risk 0.20; 95 % confidence interval: 0.07-0.57). Requirement for dialysis was not significantly different between the NAC group and the control group.
CONCLUSIONS: This review provides evidence of the efficacy of NAC in preventing the incidence of CIN and recommends that NAC be more widely used in high-risk patients undergoing contrast-enhanced CT. On the basis of the evidence reviewed, further research involving large RCTs may be warranted.
BACKGROUND: Contrast-induced nephropathy (CIN) is one of the common causes of acute renal insufficiency after contrast procedures. Whether intravenous N-acetylcysteine (NAC) is beneficial for the prevention of contrast-induced nephropathy is uncertain. In this meta-analysis of randomized controlled trials, we aimed to assess the efficacy of intravenous NAC for preventing CIN after administration of intravenous contrast media.
STUDY DESIGN: Relevant studies published up to September 2012 that investigated the efficacy of intravenous N-acetylcysteine for preventing CIN were collected from MEDLINE, OVID, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and the conference proceedings from major cardiology and nephrology meetings. The primary outcome was CIN. Secondary outcomes included renal failure requiring dialysis, mortality, and length of hospitalization. Data were combined using random-effects models with the performance of standard tests to assess for heterogeneity and publication bias. Meta-regression analyses were also performed.
RESULTS: Ten trials involving 1916 patients met our inclusion criteria. Trials varied in patient demographic characteristics, inclusion criteria, dosing regimens, and trial quality. The summary risk ratio for contrast-induced nephropathy was 0.68 (95% CI, 0.46 to 1.02), a nonsignificant trend towards benefit in patients treated with intravenous NAC. There was evidence of significant heterogeneity in NAC effect across studies (Q = 17.42, P = 0.04; I(2) = 48%). Meta-regression revealed no significant relation between the relative risk of CIN and identified differences in participant or study characteristics.
CONCLUSION: This meta-analysis showed that research on intravenous N-acetylcysteine and the incidence of CIN is too inconsistent at present to warrant a conclusion on efficacy. A large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for intravenous NAC in CIN prevention.
BACKGROUND: N-Acetylcysteine, theophylline, and other agents have shown inconsistent results in reducing contrast-induced nephropathy.
PURPOSE: To determine the effect of these agents on preventing nephropathy.
DATA SOURCES: Relevant randomized, controlled trials were identified by computerized searches in MEDLINE (from 1966 through 3 November 2006), EMBASE (1980 through November 2006), PubMed, Web of Knowledge (Current Contents Connect, Web of Science, BIOSIS Previews, and ISI Proceedings for the latest 5 years), and the Cochrane Library databases (up to November 2006). Databases were searched for studies in English, Spanish, French, Italian, and German.
STUDY SELECTION: Randomized, controlled trials that administered N-acetylcysteine, theophylline, fenoldopam, dopamine, iloprost, statin, furosemide, or mannitol to a treatment group; used intravenous iodinated contrast; defined contrast-induced nephropathy explicitly; and reported sufficient data to construct a 2 x 2 table of the primary effect measure.
DATA EXTRACTION: Abstracted information included patient characteristics, type of contrast media and dose, periprocedural hydration, definition of contrast-induced nephropathy, and prophylactic agent dose and route.
DATA SYNTHESIS: In the 41 studies included, N-acetylcysteine (relative risk, 0.62 [95% CI, 0.44 to 0.88]) and theophylline (relative risk, 0.49 [CI, 0.23 to 1.06]) reduced the risk for contrast-induced nephropathy more than saline alone, whereas furosemide increased it (relative risk, 3.27 [CI, 1.48 to 7.26]). The remaining agents did not significantly affect risk. Significant subgroup heterogeneity was present only for N-acetylcysteine. No publication bias was discerned.
LIMITATIONS: All trials evaluated the surrogate end point of contrast-induced nephropathy as the primary outcome. The lack of a statistically significant renoprotective effect of theophylline may result from insufficient data or study heterogeneity. True study quality remains uncertain.
CONCLUSION: N-acetylcysteine is more renoprotective than hydration alone. Theophylline may also reduce risk for contrast-induced nephropathy, although the detected association was not significant. Our data support the administration of N-acetylcysteine prophylaxis, particularly in high-risk patients, given its low cost, availability, and few side effects.
BACKGROUND: Contrast-induced nephropathy (CIN) following coronary angiography increases morbidity and mortality. Randomized trials of small sample size have evaluated whether N-acetylcysteine (NAC) prevents CIN in patients with renal dysfunction.
METHODS: To conduct a meta-analysis of the randomized trials the following databases were searched: MEDLINE (1966-2003), Cochrane Controlled Trials Register, ACP Journal Club online, published abstracts presented at the major cardiology and nephrology meetings, references from reviews. Two authors independently evaluated all relevant randomized trials. Eligibility criteria were (1) randomized placebo controlled trials of NAC, (2) patients with impaired renal function (creatinine >1.2 mg/dL) undergoing coronary angiography, (3) patients receiving intravenous fluids and low-osmolarity nonionic contrast media, (4) the primary outcome was CIN (increases in creatinine of either at least 0.5 mg/dL or 25% from baseline to 48 hours). Of 589 trials reviewed 3 disagreements were easily resolved by mutual discussion and 13 were selected. Data extraction included patient characteristics, intravenous fluid regimen, type and dose of contrast media, dosing regimen, creatinine at baseline and 48 hours and CIN requiring dialysis.
RESULTS: Four of the 13 trials reported statistically significant results. In meta-analysis of the 13 trials, which included 1892 patients, the RR was 0.68 (95%CI, 0.46-1.01). The addition of the trial of patients undergoing computerized tomography, which had formulated the hypothesis, yielded a statistically significant reduction (RR 0.64 [95%CI 0.42-0.96]) as did an earlier meta-analysis of 7 trials.
CONCLUSIONS: Our meta-analysis of the most currently available randomized data concerning NAC before coronary angiography to prevent CIN in patients with impaired renal function is neither conclusive nor provides proof beyond a reasonable doubt to influence clinical practice and public policy. The intervention has minimal toxicity but the width of the 95% CI remains compatible with a range from a large benefit to none at all. In addition, the trials used change in creatinine as the measure of outcome. Further randomized trials of large sample size and with clinical outcomes will add importantly relevant information to the totality of evidence and allow the most rational clinical decisions for individual patients as well as policy decisions for the health of the general public.
The objectives of this study was to assess the overall effect of N-acetylcysteine (NAC) in preventing radiocontrast-induced nephropathy (RCIN) using all available data in the literature. RCIN is associated with increased morbidity and mortality. Existing randomized trials of NAC are small and show inconsistent results. Prior meta-analyses do not include data from the most current studies. We used standard search protocols to identify all published articles and abstracts of prospective trials using NAC with fluid hydration compared to hydration alone in patients with chronic renal insufficiency undergoing contrast procedures. A rise in serum creatinine by 0.5 mg/dl or 25% above baseline at 48-72 hr after contrast exposure was used as the primary outcome. We identified 14 trials of NAC with 1,584 patients published as full-text articles. Using a random-effects model, the use of oral NAC resulted in a significant reduction in the risk for developing RCIN (RR = 0.57; 95% CI = 0.37-0.84; P = 0.01). This finding did not significantly change in a fixed-effect model (RR = 0.55; 95% CI = 0.42-0.73) or when the data were reanalyzed using only randomized trials in all forms (i.e., articles and abstracts; RR = 0.67; 95% CI = 0.47-0.95). We identified only one important difference between the positive and the negative studies: the cumulative exposure to contrast media (174 vs. 152 ml). Metaregression did not show a significant relationship between contrast volume and the RR of developing RCIN (P > 0.10). In the trials showing benefit for NAC, the treated patients' postprocedure creatinine unexpectedly decreased by 0.21 mg/dl (95% CI = 0.33-0.08). Prophylaxis with NAC significantly reduces the risk for RCIN. The reasons for improvement in serum creatinine in patients treated with NAC are unclear, but may include improved renal blood flow due to NAC and/or vigorous hydration.
It is unclear whether N-acetylcysteine is useful in preventing contrast-induced nephropathy in patients undergoing coronary angiography. Because of different inclusion and exclusion criteria and different definitions of studied parameters, various studies have reported different outcomes. A systematic search was done using PubMed, Ovid, and the Cochrane library, and studies were pooled after strict inclusion and exclusion criteria. Separate analysis was conducted for all endpoints including only studies that used an N-acetylcysteine (NAC) dose of 600 mg, and another separate analysis was conducted for all endpoints including only studies that used oral route NAC to study how the dose and route of administration of NAC affect the outcomes. The results of the pooled analysis significantly favored the use of NAC to prevent contrast-induced nephropathy in patients undergoing coronary angiography but failed to show any significant benefit in terms of creatinine levels preangiography and postangiography, need for dialysis, and all-cause mortality. The effects of route and dose of NAC did not show any significant difference except in respect to incidence of postcatheterization nephropathy. This study shows that NAC may not have any impact on clinical outcomes after peripheral or coronary artery catheterization and that dose and route do not seem to have any effect on these outcomes.
