Among doctors, it is widely believed that a class of drugs called statins, which are used to lower cholesterol, might help patients tolerate the stress of cardiac surgery.
Not so, according to a five-year, placebo-controlled, double-blinded randomized clinical trial conducted at Vanderbilt University Medical Center, published today in the Journal of the American Medical Association.
Nationally, one-fourth of cardiac surgery patients suffer acute kidney injury (AKI) following their procedure. The study tracked the incidence of AKI following cardiac surgery in 653 patients, half of whom were randomized to high-dose atorvastatin treatment and half of whom were randomized to placebo.
Atorvastatin (brand name Lipitor) didn’t reduce risk of AKI.
“If a patient is not receiving statin therapy, if they’re naïve when they come for cardiac surgery, these data do not support the initiation of statins to limit kidney injury,” said study author Frederic (Josh) Billings IV, M.D., M.Sc., assistant professor of Anesthesiology and Medicine.
The study was stopped early, but in two stages. After 546 patients completed the study, due to safety considerations it was stopped in patients naïve to statin treatment. And three months later it was stopped altogether, because, by that point, the futility of using atorvastatin to benefit cardiac surgery outcomes was established.
This isn’t the outcome the investigators expected.
“In terms of reducing cardiovascular disease, statins are known to provide benefits beyond what would be expected from their effect on cholesterol levels: lipid-lowering-independent effects, so-called,” Billings said. In cell cultures and in preclinical studies, some of these independent effects have been discovered to involve decreased oxidative stress.
A prior study by Billings and colleagues had demonstrated that oxidative stress may be an important mechanism for kidney injury in cardiac surgery patients.
“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. That was the rationale for this study,” Billings said.
Among the study’s total 198 statin-naïve patients, no statistically significant effects on AKI rates were established, but at the time the study was halted, compared to placebo, elevated blood concentration of creatinine, a marker of decreased kidney function, rose higher from baseline among those randomized to atorvastatin. And among the 36 statin-naïve patients who entered the study with chronic kidney disease, those randomized to atorvastatin suffered postop AKI at more than three times the rate of those randomized to placebo.
“We would hypothesize that other statins would pose similar results,” Billings said.
According to Billings, starting a statin prior to cardiac surgery is a common practice, if the patient has traditional risk factors for cardiovascular disease. He suggests that statin initiation should instead occur several days after surgery.
“The most conservative conclusion from this study is simply that statins aren’t beneficial for preventing AKI in cardiac surgery patients,” Billings said. “Does starting patients on statins just before surgery actually cause harm? It may.
“For the long term, patients need these drugs. Should they be introduced right before surgery? These data suggest that they shouldn’t.”
Billings stressed that this study has no implications for patients who use statins for long-term management of cholesterol and cardiovascular disease. The significant benefits of these drugs in preventing stroke and heart disease have been established.
For patients already on a statin, short-term withdrawal or continuation of the drug through surgery appears not to affect AKI risk.
Joining Billings in the study were Patricia Hendricks, R.N., Jonathan Schildcrout, Ph.D., Yaping Shi, M.S., Michael Petracek, M.D., John Byrne, M.D., and Nancy Brown, M.D.
The study was supported by grants from the National Institutes of Health (GM102676, GM112871, ES015855 and RR024975).