The largest study of the group with positive findings (n=2998) found a significant reduction with statin administration in the general study population but not in the post-hoc subgroup analyses of statin naïve versus statin non-naïve participants.145 This study had a high risk of bias based on the five criteria described in the methods for assessing risk of bias for individual studies (Appendix F), but its effect estimate was in the same direction as the other three studies in the meta-analysis (which had fewer study limitations). An additional study142 evaluated the occurrence of CIN in the nonstandard time frame of 5 days and therefore was not included in the meta-analysis; this study did not demonstrate a clinically or statistically significant difference between the intervention and control arms (Figure 10). In a meta-analysis of the eight studies with a CIN endpoint ranging from 48 to 72 hours after contrast media administration,138,139,144,145,152-155 the pooled estimate of the effect of statin plus IV fluids compared with IV fluids alone demonstrated a clinically important but statistically insignificant reduced risk of CIN with statin use (pooled risk ratio 0.68; 95% CI: 0.39 to 1.20) . A sensitivity analysis demonstrated that no study unduly influenced the overall statistical significance of the pooled estimate, and a stratified analysis showed no substantial difference in estimation of effect by statin type, as the point estimates of effect were all clinically important. No statin type had a 95% CI that was fully in the range consistent with a clinically important effect The estimate for rosuvastatin, from four studies (risk ratio 0.69; 95% CI: 0.47 to 1.02) was clinically important, but the CI was wide enough to not rule out the possibility of an unimportant effect.145,152,153,155 The estimate for atorvastatin, three studies (risk ratio 0.41; 95% CI: 0.02 to 2.71) was clinically important, but the CI was wide enough to not rule out the possibility of an unimportant effect. While the point estimate of the effect of simvastatin (risk ratio 0.75; 95% CI: 0.17 to 3.28) was not clinically important, the confidence interval was so wide that we cannot rule out the possibility of a clinically important benefit or harm. Note that atorvastatin was the only drug for which there was more than one study. A meta-regression was not conducted, due to the small number of studies. We saw no trends in the data that pointed to differences in groups by age, kidney function, diabetes status, or sex. The studies on statins had a medium risk of bias, and consistently showed a benefit in reducing CIN in favor of the statin drug with a relatively precise resulting estimate of the effect. Harbord’s modified test for small study effects did not demonstrate evidence of asymmetry in results by study precision (bias coefficient of -1.49, standard error of 1.11, p=0.227). We concluded that the strength of evidence was low for demonstrating that a statin plus IV fluids was more effective than IV fluids alone at preventing CIN (Table 6; see Appendixes F and G for study limitations). When evaluating the efficacy of statin administration plus N-acetylcysteine plus IV saline (or IV sodium bicarbonate) compared with N-acetylcysteine plus IV fluids (or IV sodium bicarbonate) in the prevention of CIN, four studies137,141,146,156 found both a statistically significant and clinically important reduction in CIN (above our 25% threshold for a minimally important difference) in the statin arm. One study showed a statistically non-significant (p=0.86) reduction that was clinically insignificant.142 In a meta-analysis of studies with a CIN endpoint,137,141,142,146 the pooled estimate of the effect of statin plus N-acetylcysteine plus IV fluids (saline or sodium bicarbonate) compared with N-acetylcysteine plus IV fluids (saline or sodium bicarbonate) demonstrated a clinically important and statistically significant reduced risk of CIN with statin use (pooled risk ratio 0.52; 35 95% CI: 0.29 to 0.93) with a number needed to treat of 18 (95% CI: 13.44 to 34.72) (see Figure 11). However, the CI for the risk ratio was wide enough that we cannot rule out the possibility of a clinically unimportant difference. A meta-regression was not conducted due to the small number of studies. We saw no trends in the data that pointed to differences in groups by age, kidney function, diabetes status, or sex. Harbord’s modified test for small study effects did not demonstrate evidence of asymmetry in results by study precision (bias coefficient of -0.63, standard error of 1.68, p=0.735). We concluded that the strength of evidence was low for demonstrating that a statin plus N-acetylcysteine plus IV fluids was more effective than Nacetylcysteine plus IV fluids at preventing CIN, when considering study limitations, directness, consistency, and precision (Table 6; see Appendixes F and G for study limitations). One study comparing atorvastatin to IV saline140 did not report on CIN outcomes. This study reported on the change in serum creatinine and estimated glomerular filtration rate. No difference was reported in serum creatinine levels 48 hours after the procedure, and estimated glomerular filtration rate was significantly lower in the atorvastatin group 48 hours after the procedure (Appendix E, Evidence Table E-20). Two studies reported on the incidence of CIN in participants receiving a statin versus a statin plus probucol.147,150 Han, 2013150