High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery

 

Flora Le, Mercer University College of Pharmacy

A review of seven studies showed that pre-operative statin treatment was not associated with a reduction in postoperative acute kidney injury (AKI), need for renal replacement therapy, or mortality in adults who required cardiac bypass.  [1]

A systematic review of 26 studies concluded that perioperative statin therapy reduced the incidence of short- and long-term postoperative renal dysfunction, the need for renal replacement therapy, and the incidence of postoperative acute kidney injury in patients who underwent cardiac surgery. [2]

Title: High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery
Design Double-blinded, placebo-controlled, randomized clinical trial; N= 617
Objective To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce acute kidney injury (AKI) following cardiac surgery
Study Groups Patients naive to statin treatment (n = 199): patients naive to statin therapy receiving statin (n= 102); placebo (n = 97)

 

Patients already taking a statin prior to study enrollment (n = 416): patients receiving statin therapy (n = 206); placebo (n = 210)

Methods Patients naive to statin treatment were randomized to receive atorvastatin 80 mg the day prior to surgery, atorvastatin 40 mg the morning of surgery (at least three hours prior to surgery), and atorvastatin 40 mg daily at 10 AM following surgery for the duration of hospitalization or to a matching placebo regimen.  Patients already taking a statin continued taking their pre enrollment statin until the day of surgery and resumed taking their previously prescribed statin on postoperative day two. On the day of surgery, patients were randomly assigned to atorvastatin 80 mg at least three hours prior to surgery and atorvastatin 40 mg the day after surgery at ten or to a matching placebo regimen.
Duration November 2009 to October 2014
Primary Outcome Measure Diagnosis of AKI according to criteria from the Acute Kidney Injury Network, specifically an increase of 0.3 mg/dL in serum creatinine concentration or the initiation of renal replacement therapy within 48 hours of surgery
Baseline Characteristics Characteristics Atorvastatin
(n= 308)
Placebo
(n= 307)
Age, (median years) 66 67
Female, (no.) 94 94
Black race, (no.) 11 15
Congestive heart failure, (no.) 129 114
Left ventricular ejection fraction, (median %) 60 55
Atrial fibrillation, (no.) 73 68
Diabetes, (no.) 104 98
Creatinine, (mg/ dL) 1.10 1.02
Glomerular filtration rate, (ml/ min) 74 71
Low- density lipoprotein, (mg/ dL) 68 74
Total cholesterol, (mg/ dL) 125 132
Results Acute kidney injury occurred in 20.8% in the atorvastatin group versus 19.5% in the placebo group (95% [CI] 0.78 to 1.46]; p = 0.75).  Among patients naive to statin treatment, AKI occurred in 21.6% in the atorvastatin group versus 13.4% in the placebo group (95% [CI] 0.86 to 3.01; p = 0.15).  The serum creatinine concentration increased by a median of 0.11 mg/dL in the atorvastatin group versus by a median of 0.05 mg/dL in the placebo group (95% [CI] 0.01 to 0.15 mg/dL]; p = 0.007).  Among patients already taking a statin, AKI occurred in 20.4% in the atorvastatin group versus 22.4% in the placebo group (95% [CI] 0.63 to 1.32]; p = 0.63).
Adverse Events Common Adverse Events: muscle myalgia (1.9%)
Serious Adverse Events: cardiac arrests (2%), severe infections (1.9%), severe peripheral vascular ischemia (0.64%)
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions 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.

In this study, the use of high- dose perioperative atorvastatin in cardiac surgery did not decrease the risk of acute kidney injury unlike other studies, which found statins to be beneficial in decreasing the risk of AKI.  A limitation to this finding is the small number of patients in the subgroup with chronic kidney disease and are naive to statin treatment.  For future studies, investigating a larger patient population with chronic kidney disease that is naive to statin therapy should be assessed.  Use of a lower dose statin therapy could be investigated as a second option in determining if statins can decrease the risk of AKI.

References

  1. Lewicki M, Ng I, Schneider AG. HMG CoA reductase inhibitors (statins) for preventing acute kidney injury after surgical procedures requiring cardiac bypass. Cochrane Database Syst Rev. 2015;3:CD010480.
  2. Wang J, Gu C, Gao M, Yu W, Yu Y. Preoperative Statin Therapy and Renal Outcomes After Cardiac Surgery: A Meta-analysis and Meta-regression of 59,771 Patients. Can J Cardiol. 2015;31(8):1051-60.
  3. Billings FT, Hendricks PA, Schildcrout JS, et al. High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial. JAMA. 2016;315(9):877-88.

 

 

 

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