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Contrast-Induced Nephropathy; Comparative Effects of Different Contrast Media
To evaluate the comparative effects of different types of contrast media with respect to the risk of developing contrast-induced nephropathy (CIN) by synthesizing the current literature.
We searched for original studies in MEDLINE®, Embase®, and the Cochrane Library through October 1, 2014. We also searched for studies in ClinicalTrials.gov and the Scopus database.
Two reviewers independently reviewed each article to identify randomized controlled trials (RCTs) that reported on CIN-related outcomes in patients after receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media (IOCM). We included head-to-head comparisons of one LOCM versus another LOCM or of LOCM versus IOCM. (Only 1 IOCM is currently available in the United States.) For each study, one reviewer extracted the data and a second reviewer verified the accuracy. Both reviewers assessed the risk of bias for each study. Together, the reviewers graded the strength of evidence for the comparisons and outcomes of interest. We quantitatively pooled the results of studies that were sufficiently similar, using a 25-percent relative risk reduction as the threshold for a minimally important difference.
We identified five RCTs that compared two or more LOCMs, including two studies of intra-arterial administration, two studies of intravenous administration, and one study examining both routes. We identified 25 RCTs that compared IOCM with LOCM, including 18 studies of intra-arterial administration and 7 studies of intravenous administration. No study comparing LOCMs reported a statistically significant or clinically important difference between study arms, and the overall analysis did not suggest that any one LOCM was superior to another. In a meta-analysis, we found a borderline significant reduction in short-term CIN risk with IOCM compared with a diverse group of LOCMs (pooled relative risk, 0.80; 95% confidence interval [CI], 0.65 to 0.99, p=0.045). When the analysis was stratified by route of administration, the aggregate pooled relative risk was 0.80 (95% CI, 0.64 to 1.01) for intra-arterial and 0.84 (95% CI, 0.42 to 1.71) for intravenous. In studies that investigated IOCM versus LOCM, the outcomes of mortality, cardiovascular outcomes, need for renal replacement therapy, and imaging quality or diagnostic accuracy showed no significant difference between groups. One study comparing different LOCMs investigated the outcomes of death and adverse events, and found no difference between groups.
We found low strength of evidence that the risk of CIN did not differ between LOCMs, and moderate strength of evidence that IOCM had a slightly lower risk of CIN than LOCM. The lower risk was not clinically important and just reached statistical significance.
Contrast-Induced Nephropathy; Comparative Effectiveness of Preventive Measures
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).
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.
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.
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).
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.