magnitude of effect was weak. Although usual care often involves administration of IV fluids, the evidence was insufficient to support a conclusion about the relative effectiveness of IV versus oral fluids, or whether fluids should be given before or after the procedure. Despite the large body of evidence on N-acetylcysteine, the SOE was low, primarily because of limitations in the quality of many of the studies and inconsistency in results across studies, with the possibility of an effect too small to be clinically meaningful. The low SOE helps to explain why N-acetylcysteine is not used more often in clinical practice and why professional organizations offer differing recommendations about the use of N-acetylcysteine to prevent CIN. The joint American College of Cardiology/American Heart Association 2012 guideline recommends against use of N-acetylcysteine for patients receiving intra-arterial contrast in cardiac procedures. 12 In comparison, the 2012 Kidney Disease: Improving Global Outcomes ES-9 (KDIGO) Clinical Practice Guideline for Acute Kidney Injury suggests using oral Nacetylcysteine with IV fluids in patients at increased risk for CIN, while acknowledging that the quality of evidence is very low. 13 Although N-acetylcysteine is inexpensive and appears to be safe, the evidence may not be strong enough to support a firm policy of routine use, especially in the absence of stronger evidence on clinical outcomes other than the incidence of CIN. For clinicians who want to reduce the risk of CIN in patients receiving LOCM or IOCM, evidence of potential benefit was seen with use of a statin plus N-acetylcysteine compared with N-acetylcysteine alone. The aggregate risk ratio was 0.52, suggesting a nearly 50 percent relative reduction in risk of CIN, but the SOE was low. Despite previous systematic reviews highlighting the existence of this evidence on the effectiveness of statins in lowering the risk of CIN, statins are not used routinely in clinical practice to prevent CIN. Furthermore, we are not aware of any professional guidelines recommending their use for this indication. It is possible that the findings reported in the studies of statins could be partly explained by a direct effect of statins on glomerular filtration rate that is independent of a protective effect on kidney function, as has been reported in one study.14 However, with increasing recognition of the beneficial cholesterolindependent vascular effects of statins, it may be time to reassess the role of statins in preventing CIN, especially since statins are readily available, easy to administer, and relatively inexpensive. Our primary analysis showed that IV sodium bicarbonate did not produce a clinically important decrease in CIN compared with IV saline, contrary to the conclusion of a recent metaanalysis. 15 This difference in conclusions can be attributed to the fact that the other meta-analysis included five studies that used a combination of IV sodium bicarbonate and N-acetylcysteine, which we excluded from our analysis of the effects of sodium bicarbonate. In a sensitivity analysis, we found low SOE for a clinically important benefit in decreasing CIN when sodium bicarbonate was used in studies with LOCM, but the difference was not statistically significant. This finding suggests that IV sodium bicarbonate could have a role in preventing CIN, but only in patients receiving LOCM. Future Research Future studies of the comparative effectiveness of interventions for preventing CIN should stratify patients according to their baseline risk of CIN, especially since it may be difficult to detect a treatment effect in patients having a low risk of CIN. Patients with normal or nearnormal serum creatinine may have a lower risk for developing CIN than those with higher serum creatinine levels. Also, patients with risk factors for CKD have a higher risk of developing CIN than patients without such risk factors. Unfortunately, we had a limited ability to stratify the analysis according to baseline risk because almost all studies had a mixed patient population and did not report the results separately by baseline risk. More research could help to strengthen the evidence about whether N-acetylcysteine or IV sodium bicarbonate would be beneficial in a particular clinical context, such as patients with an increased risk of developing CIN who will be receiving LOCM. Given the evidence from our primary analysis showing that IV sodium bicarbonate did not produce a clinically important reduction in CIN compared with IV saline and did not differ in head-to-head comparisons with N-acetylcysteine, it may be difficult to justify additional RCTs of IV sodium bicarbonate unless they focus on particular groups of patients having a higher risk of developing CIN. The clinically important benefit of statins demonstrated in this analysis provides a rationale for further studies investigating whether the effect differs by statin dose, timing of administration, type of contrast media, or baseline risk of the patient population. Further ES-10 investigation into the findings on statins versus IV saline could be performed through examination of the possible effect of risk modifiers, such as baseline kidney function, concurrent use of nephrotoxic medications, and patient demographics. Future studies could explore the effect of statins on reducing CIN when contrast media are administered