Compared with placebo, high-dose atorvastatin did not decrease risk for acute kidney injury after cardiac surgery, according to findings presented at the Critical Care Congress and published in JAMA.
Researchers tested their hypothesis that short-term perioperative high-dose atorvastatin would reduce acute kidney injury after cardiac surgery by conducting a randomized, double blind, placebo-controlled trial of patients who underwent cardiac surgery between November 2009 and October 2014 at Vanderbilt University Medical Center.
Patients who had never before taken a statin were randomly assigned a regimen of 80 mg atorvastatin the day before surgery, 40 mg atorvastatin the morning of the surgery and 40 mg/day atorvastatin after surgery, or a matching placebo regimen. Patients taking a statin before enrollment stayed on their current regimen until the day of the surgery and then were randomly assigned 80 mg atorvastatin the morning of surgery and 40 mg atorvastatin the morning after surgery or a matching placebo regimen. On the second day after surgery, those who had been taking a statin resumed their previous regimen.
The primary outcome was acute kidney injury, defined as a serum creatinine concentration rise of 0.3 mg/dL within 48 hours after surgery.
Trial halted early
Frederic T. Billings IV, MD, MSc, and colleagues reported that the trial’s data and safety monitoring board recommended stopping the trial in those naive to statin treatment because those with chronic kidney disease assigned high-dose atorvastatin had an increased rate of acute kidney injury, and later recommended stopping the trial for futility after 615 patients completed it.
Among the first 615 patients in the overall study (median age, 67 years; 30.6% women), acute kidney injury was reported in 20.8% of the atorvastatin group vs. 19.5% of the placebo group (RR = 1.06; 95% CI, 0.78-1.46).
Among the 199 patients who had never before taken a statin, acute kidney injury occurred in 21.6% of the atorvastatin group vs. 13.4% of the placebo group (RR = 1.61; 95% CI, 0.86-3.01), Billings, from the departments of anesthesiology and medicine, Vanderbilt University School of Medicine, and colleagues found.
In the statin-naive cohort, median serum creatinine concentration increased by 0.11 mg/dL (10th-90th percentile, –0.11 to 0.56) in the atorvastatin group vs. 0.5 mg/dL (10th-90th percentile, –0.12 to 0.33) in the placebo group (mean difference, 0.08 mg/dL; 95% CI, 0.01-0.15), according to the researchers.
In the cohort of patients already taking a statin, the rate of acute kidney injury was 20.4% in the atorvastatin group and 22.4% in the placebo group (RR = 0.91; 95% CI, 0.63-1.32), they found.
Stay the course
In a related editorial published in JAMA, Rinaldo Bellomo, MBBS(Hons), MD, FRACP, FCICM, wrote, “These findings provide important additional evidence that continuing perioperative statin therapy is likely safe, rational, easy, inexpensive and perhaps slightly protective against [acute kidney injury] for patients undergoing cardiac surgery. In contrast, the results suggest that initiating perioperative statin therapy in patients naive to statin treatment undergoing cardiac surgery may be injurious to the kidney.”
Bellomo, from the department of the intensive care unit at Austin Hospital and the school of medicine at the University of Melbourne, Australia, concluded that, “In the absence of any other convincing evidence of benefit, these findings strongly argue in favor of not administering statins to patients naïve to statin treatment about to undergo cardiac surgery.” – by Erik Swain
Billings IV FT, et al. Hot Topics and Late-Breaking Science: Journal Submissions. Presented at: Critical Care Congress; Feb, 20-24, 2016; Orlando, Fla.
Bellomo R. JAMA. 2016;doi:10.1001/jama.2016.0245.
Billings IV FT, et al. JAMA. 2016;doi:10.1001/jama.2016.0548.
Disclosure: Billings and Bellomo report no relevant financial disclosures. One researcher reports receiving grants from New Haven Pharmaceuticals and Shire Pharmaceuticals and personal fees from Alnylam and Novartis.