High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery
Authors: Frederic T. Billings, Patricia A. Hendricks, Jonathan S. Schildcrout, Yaping Shi, Michael R. Petracek, John G. Byrne, Nancy J. Brown
Journal: JAMA (2016)

<h3>Importance</h3> Statins affect several mechanisms underlying acute kidney injury (AKI). <h3>Objective</h3> To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery. <h3>Design, Setting, and Participants</h3> Double-blinded, placebo-controlled, randomized clinical trial of adult cardiac surgery patients conducted from November 2009 to October 2014 at Vanderbilt University Medical Center. <h3>Interventions</h3> Patients naive to statin treatment (n = 199) were randomly assigned 80 mg of atorvastatin the day before surgery, 40 mg of atorvastatin the morning of surgery, and 40 mg of atorvastatin daily following surgery (n = 102) or matching placebo (n = 97). Patients already taking a statin prior to study enrollment (n = 416) continued taking the preenrollment statin until the day of surgery, were randomly assigned 80 mg of atorvastatin the morning of surgery and 40 mg of atorvastatin the morning after (n = 206) or matching placebo (n = 210), and resumed taking the previously prescribed statin on postoperative day 2. <h3>Main Outcomes and Measures</h3> Acute kidney injury defined as an increase of 0.3 mg/dL in serum creatinine concentration within 48 hours of surgery (Acute Kidney Injury Network criteria). <h3>Results</h3> The data and safety monitoring board recommended stopping the group naive to statin treatment due to increased AKI among these participants with chronic kidney disease (estimated glomerular filtration rate &lt;60 mL/min/1.73 m<sup>2</sup>) receiving atorvastatin. The board later recommended stopping for futility after 615 participants (median age, 67 years; 188 [30.6%] were women; 202 [32.8%] had diabetes) completed the study. Among all participants (n = 615), AKI occurred in 64 of 308 (20.8%) in the atorvastatin group vs 60 of 307 (19.5%) in the placebo group (relative risk [RR], 1.06 [95% CI, 0.78 to 1.46];<i>P</i> = .75). Among patients naive to statin treatment (n = 199), AKI occurred in 22 of 102 (21.6%) in the atorvastatin group vs 13 of 97 (13.4%) in the placebo group (RR, 1.61 [0.86 to 3.01];<i>P</i> = .15) and serum creatinine concentration increased by a median of 0.11 mg/dL (10th-90th percentile, −0.11 to 0.56 mg/dL) in the atorvastatin group vs by a median of 0.05 mg/dL (10th-90th percentile, −0.12 to 0.33 mg/dL) in the placebo group (mean difference, 0.08 mg/dL [95% CI, 0.01 to 0.15 mg/dL];<i>P</i> = .007). Among patients already taking a statin (n = 416), AKI occurred in 42 of 206 (20.4%) in the atorvastatin group vs 47 of 210 (22.4%) in the placebo group (RR, 0.91 [0.63 to 1.32];<i>P</i> = .63). <h3>Conclusions and Relevance</h3> Among patients undergoing cardiac surgery, high-dose perioperative atorvastatin treatment compared with placebo did not reduce the risk of AKI overall, among patients naive to treatment with statins, or in patients already taking a statin. These results do not support the initiation of statin therapy to prevent AKI following cardiac surgery. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00791648