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Original Investigation | Caring for the Critically Ill Patient

High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery A Randomized Clinical Trial

Frederic T. Billings IV, MD, MSc1,2; Patricia A. Hendricks, RN1; Jonathan S. Schildcrout, PhD3; Yaping Shi, MS3; Michael R. Petracek, MD4; John G. Byrne, MD5; Nancy J. Brown, MD2
[+] Author Affiliations
1Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee
2Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
3Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee
4Department of Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee
5Department of Cardiac Surgery, Harvard University School of Medicine, Boston, Massachusetts
JAMA. 2016;315(9):877-888. doi:10.1001/jama.2016.0548.
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Importance  Statins affect several mechanisms underlying acute kidney injury (AKI).

Objective  To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery.

Design, Setting, and Participants  Double-blinded, placebo-controlled, randomized clinical trial of adult cardiac surgery patients conducted from November 2009 to October 2014 at Vanderbilt University Medical Center.

Interventions  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.

Main Outcomes and Measures  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).

Results  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 <60 mL/min/1.73 m2) 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]; P = .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]; P = .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]; P = .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]; P = .63).

Conclusions and Relevance  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.

Trial Registration  clinicaltrials.gov Identifier: NCT00791648

Figures in this Article

Figures

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Figure 1.
Recruitment, Randomization, and Follow-up for the Statin Acute Kidney Injury Cardiac Surgery RCT

RCT indicates randomized clinical trial.

aThese are approximate data.

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Figure 2.
Efficacy of Treatment to Prevent Acute Kidney Injury (AKI) in All Patients and Prespecified Subgroups

Absolute differences are the estimated differences in proportions between the atorvastatin and placebo groups derived from model transformations. Quasi-Poisson log-linear regression was used to calculate the estimates and 95% CIs. The estimates should be interpreted as the relative risk of treatment for the primary end point of AKI. The Pearson χ2 test was used to calculate the P values.

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