High-dose statins don't prevent kidney injury after cardiac surgery

High-dose statin treatment did not reduce the risk of acute kidney injury in patients who underwent cardiac surgery, according to a study published February 23, 2016 in JAMA and simultaneously presented at the Society of Critical Care Medicine’s 45th Critical Care Congress, in Orlando, FL.

The results are a disappointment, as up to 30% of cardiac surgery patients suffer acute kidney injury after their procedure.

“In terms of reducing cardiovascular disease, statins are known to provide benefits beyond what would be expected from their effect on cholesterol levels,” said study author Frederic T. Billings IV, MD, MSc, Assistant Professor of Anesthesiology and Medicine at Vanderbilt University School of Medicine, in Nashville, TN.

One of those benefits could be decreased oxidative stress. A prior study by Dr. Billings and colleagues had demonstrated that oxidative stress may be an important mechanism for kidney injury in cardiac surgery patients. Observational studies suggested statin treatment might reduce that risk in such patients, but these studies were inconclusive and not specifically designed to test this hypothesis.

“So we thought, since we have a therapy that is common and well accepted in patients with cardiovascular disease, giving statins at high dose at the time of surgery may reduce oxidative stress and decrease kidney injury,” Dr. Billings said. “That was the rationale for this study.”

To that end, Dr. Billings and colleagues randomly assigned cardiac surgery patients naive to statin treatment to either placebo or to 80 mg of atorvastatin the day before surgery, 40 mg of atorvastatin the morning of surgery, and 40 mg of atorvastatin daily following surgery.

Patients already taking a statin prior to the study continued taking it until the day of surgery, and were then randomly assigned to either placebo or to 80 mg of atorvastatin the morning of surgery and 40 mg of atorvastatin the morning after. On postoperative day 2, they resumed taking their previously prescribed statin.

However, the data and safety monitoring board recommended stopping the study early due to increased kidney injury, but only for the group naive to statin treatment who received atorvastatin. The board later recommended stopping the study altogether due to the futility of using atorvastatin to benefit cardiac surgery outcomes.

By this point, 615 participants had completed the study. Overall, acute kidney injury occurred in similar numbers of patients in the atorvastatin group (21%) and in the placebo group (19.5%). Among patients naive to statin treatment, acute kidney injury occurred more in the atorvastatin group (22%) than in the placebo group (13%). In addition, the atorvastatin group had a greater average increase in serum creatinine concentration than the placebo group.

Among patients already taking a statin, acute kidney injury occurred in 20% of those in the atorvastatin group compared with 22% in the placebo group.

Also, 36 statin-naive patients already had chronic kidney disease when they entered the study. Results showed that those randomized to atorvastatin had more than three times the rate of postop acute kidney injury compared with those given placebo.

“We would hypothesize that other statins would pose similar results,” Dr. Billings said.

He added that this study has no implications for patients who use statins for long-term management of cholesterol and cardiovascular disease. For patients already on a statin, short-term withdrawal or continuation of the drug during surgery doesn’t appear to affect risk of kidney injury, he said.