Statin Does Not Ward Off Acute Kidney Injury in Cardiac Surgery

Marlene Busko

February 24, 2016

NASHVILLE, TN — The first large randomized controlled trial to test the hypothesis that a perioperative statin prevents acute kidney injury (AKI) in patients undergoing cardiac surgery has come up negative[1]. Specifically, in 615 patients who had cardiac surgery in the Statin Cardiac Surgery trial, those who received perioperative high-dose atorvastatin had a similar incidence of AKI as those who received placebo.

Moreover, among statin-naive patients with preexisting chronic kidney disease, perioperative statin significantly upped the risk of developing AKI, in this study by Dr Frederic T Billings (Vanderbilt University, Nashville, TN) and colleagues that was published February 23, 2016 in the Journal of the American Medical Association. It was "somewhat alarming" that these patients at highest risk of AKI with the most to gain from preventive therapies ended up with higher rates of AKI if they were given atorvastatin, Billings told heartwire from Medscape.

However, this was a small patient subgroup, he stressed. Nevertheless, he said, the study at least provides no evidence for a benefit from starting these patients on a high dose of a statin. "If a patient comes in with chest pain, for example, and needs cardiac surgery, before seeing a surgeon, cardiologists and internists [often start the patient] on a statin, aspirin, and a beta-blocker," he continued. This study suggests that clinicians should not initiate statins in statin-naive patients about to have cardiac surgery in the hopes of limiting kidney injury, according to Billings.

In an accompanying editorial[2], Dr Rinaldo Bellomo (Melbourne University, Australia) uses even stronger language. "Any use [of statins] as nephroprotective agents in patients naive to statin treatment undergoing cardiac surgery should now be abandoned," he writes.

Cardiology-Surgery Patients Commonly Develop AKI

After cardiac surgery, about 20% to 30% of patients develop AKI, defined according to the Acute Kidney Injury Network (AKIN) as a 0.3-mg/dL rise in serum creatinine within 48 hours of surgery, Billings explained. AKI is associated with a significant increase in delirium and arrhythmia and a fivefold increase in death during hospitalization, he added. Although a patient's serum creatinine typically returns to the baseline level, these patients have worse long-term kidney function.

Statins, which improve endothelial function, might prevent AKI in patients having cardiac surgery, but prior observational studies have had mixed results.

Billings and colleagues randomized and had complete data from 615 adults who had elective CABG, valvular heart surgery, or ascending-aortic surgery at their center between 2009 and 2014. The patients had a median age of 67; 31% were women, and 32% had diabetes. Half of the patients had CABG and two-thirds had valve surgery.

Of the 199 patients who were statin-naive, 102 patients received atorvastatin (80 mg before surgery, 40 mg the morning of surgery, and 40 mg daily after surgery and during hospitalization) and 97 patients received a matching placebo regimen.

Of the 416 patients who were already taking statins, 206 patients continued to take statin therapy (except that it was replaced with 80-mg atorvastatin on the day of surgery and 40-mg atorvastatin on the day after surgery), and 210 other patients received placebo instead of atorvastatin.

In the subgroup of 36 statin-naive patients with chronic kidney disease, nine of 17 patients in the atorvastatin group vs three of 19 patients in the placebo group developed AKI (P=0.03).

In August 2014, the study's data and safety monitoring board recommended that the researchers stop recruiting patients without prior statin treatment due to concerns of increased AKI, and in October 2014, it recommended stopping the study due to futility, which was done.

Efficacy of Atorvastatin vs Placebo to Prevent AKI in Cardiac-Surgery Patients

Group Atorvastatin (% with AKI) Placebo (% with AKI) RR (95% CI) P
All patients 20.8 19.5 1.06 (0.78–1.46) 0.75
Statin-naive 21.6 13.4 1.61 (0.86–3.01) 0.15
Statin users 20.4 22.4 0.91 (0.63–1.32) 0.63
CKD patients 35.7 32.6 1.09 (0.73–1.65) 0.76
Statin-naive 52.9 15.8 3.35 (1.12–10.05) 0.03
Statin users 31.3 36.8 0.85 (0.54–1.35) 0.59
AKI=acute kidney injury
CKD=chronic kidney disease
RR=relative risk

"These findings provide important additional evidence for the notion that continuing perioperative statin therapy is likely safe, rational, easy, inexpensive, and perhaps slightly protective against AKI for patients undergoing cardiac surgery," according to Bellomo. "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."

He calls for more research to find a protective agent against AKI and to unravel the mechanism of action. "Further exploration of promising or novel interventions and more studies aimed at understanding the pathogenesis of AKI following cardiac surgery remain a clinical priority and are certain to follow," he concludes.

Billings and Bellomo had no relevant financial relationships. Disclosures for the coauthors are listed in the article.

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