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

Billings, Frederic T.; Hendricks, Patricia A.; Schildcrout, Jonathan S.; Shi, Yaping; Petracek, Michael R.; Byrne, John G.; Brown, Nancy J.

doi:10.1001/jama.2016.0548

Cited by 203 publications

(176 citation statements)

References 37 publications

Supporting

Mentioning

161

Contrasting

Unclassified

Order By: Relevance

“…Eighty‐nine patients (22.8%) developed AKIN‐based AKI after surgery. Trial‐dictated atorvastatin treatment did not affect ΔSCr or the incidence of AKIN‐defined AKI 27. There was also no difference in median postoperative ΔSCr between statin‐naïve patients and long‐term statin‐using patients ( P =0.37).…”

Section: Resultsmentioning

confidence: 90%

See 1 more Smart Citation

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Smith

Blume

Linton

et al. 2017

JAHA

Self Cite

View full text Add to dashboard Cite

BackgroundAcute kidney injury (AKI) after cardiac surgery is associated with increased short‐ and long‐term mortality. Inflammation, oxidative stress, and endothelial dysfunction and damage play important roles in the development of AKI. High‐density lipoproteins (HDLs) have anti‐inflammatory and antioxidant properties and improve endothelial function and repair. Statins enhance HDL's anti‐inflammatory and antioxidant capacities. We hypothesized that a higher preoperative HDL cholesterol concentration is associated with decreased AKI after cardiac surgery and that perioperative statin exposure potentiates this association.Methods and ResultsWe tested our hypothesis in 391 subjects from a randomized clinical trial of perioperative atorvastatin to reduce AKI after cardiac surgery. A 2‐component latent variable mixture model was used to assess the association between preoperative HDL cholesterol concentration and postoperative change in serum creatinine, adjusted for known AKI risk factors and suspected confounders. Interaction terms were used to examine the effects of preoperative statin use, preoperative statin dose, and perioperative atorvastatin treatment on the association between preoperative HDL and AKI. A higher preoperative HDL cholesterol concentration was independently associated with a decreased postoperative serum creatinine change (P=0.02). The association between a high HDL concentration and an attenuated increase in serum creatinine was strongest in long‐term statin‐using patients (P=0.008) and was further enhanced with perioperative atorvastatin treatment (P=0.004) and increasing long‐term statin dose (P=0.003).ConclusionsA higher preoperative HDL cholesterol concentration was associated with decreased AKI after cardiac surgery. Preoperative and perioperative statin treatment enhanced this association, demonstrating that pharmacological potentiation is possible during the perioperative period.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00791648.

show abstract

Section: Resultsmentioning

confidence: 90%

“…Three recent, high‐quality, randomized clinical trials, including this study's parent trial, have demonstrated that perioperative statin treatment does not reduce postoperative AKI and may, in fact, be harmful 27, 39, 40. The evidence suggests that statins should not be initiated in the perioperative period to reduce AKI.…”

Section: Discussionmentioning

confidence: 87%

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Smith

Blume

Linton

et al. 2017

JAHA

Self Cite

View full text Add to dashboard Cite

show abstract

“…Intraoperative vasopressor requirement was lower in the statin group, but this did not reflect in clinical benefit. There was no evidence for toxicity in terms of creatinine kinase (CK > 5000 U) [8].Two other recent RCTs evaluated the renoprotective effect of statins in elective cardiac surgery [10,11]. The first RCT randomized 199 statin-naïve patients and 416 patients already taking statins before surgery to a short course of high-dose atorvastatin or placebo.…”

mentioning

confidence: 99%

Statins do not prevent cardiac surgery-associated AKI: is ubiquinone the missing link?

Schetz

Straaten

2016

Intensive Care Med

View full text Add to dashboard Cite

Statins have become one of the most commonly prescribed drugs worldwide in the prevention of cardiovascular disease. Most benefits are secondary to inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase) which lowers low-density lipoprotein cholesterol levels. However, statins also have cholesterolindependent, pleiotropic effects that occur within hours of initiation and include improved endothelial function, anti-apoptotic, anti-inflammatiory, antioxidant, antithrombotic, and immunomodulatory effects [1].Cardiac surgery-associated acute kidney injury (AKI) is the second most common cause of AKI in critically ill patients. It is associated with poor short-and long-term outcome [2]. Attempts at pharmacologic prevention have been disappointing. Its pathogenesis is complex, but inflammation, oxidative stress, and endothelial dysfunction are pathogenic factors [2] that could, potentially, be mitigated by the pleiotropic effects of statins. Animal models of ischemia-reperfusion indeed show a beneficial effect of statins on kidney function [3]. In patients receiving radiocontrast for coronary angiography and percutaneous coronary interventions, statins reduce the incidence of post-contrast AKI [4]. In the setting of cardiac surgery, observational trials found inconsistent results regarding the association between preoperative statin use and postoperative AKI [5,6]. A Cochrane meta-analysis of small randomized controlled trials (RCTs), mostly with high risk of bias, could, however, not find a beneficial effect of statins on AKI after cardiac surgery [7]. This meta-analysis concludes that large highquality trials are required.In an article published in Intensive Care Medicine, Park et al. report an investigator-initiated double-blind randomized placebo-controlled trial evaluating the perioperative short-term use of high-dose atorvastatin in 200 statin-naïve patients scheduled for elective valvular heart surgery [8]. The choice for valvular surgery is motivated by the high prevalence of statin use in coronary artery bypass graft (CABG) patients and the possible rebound inflammatory response due to statin withdrawal [9]. Baseline characteristics and surgical procedures were well balanced. The primary endpoint, the incidence of AKI within the first 48 h according to the Acute Kidney Injury Network (AKIN) criteria, was not affected (21 % in the statin group and 26 % in the control group; p = 0.404). Only 6 % in both groups had AKI stage 2 or 3. In addition, more sensitive markers of kidney injury (creatinine, NGAL) and inflammation (IL-18, CRP), the secondary endpoints, were comparable between groups. Intraoperative vasopressor requirement was lower in the statin group, but this did not reflect in clinical benefit. There was no evidence for toxicity in terms of creatinine kinase (CK > 5000 U) [8].Two other recent RCTs evaluated the renoprotective effect of statins in elective cardiac surgery [10,11]. The first RCT randomized 199 statin-naïve patients and 416 patients already taking statins before surgery to ...

show abstract

“…Recently, Billings and colleagues conducted the prospective double-blinded randomized controlled trial of a perioperative statin for prevention of AKI following cardiac surgery (5). Their hypothesis was that perioperative statin would reduce AKI following cardiac surgery by 30% as compared to placebo with an assumed AKI incidence of 27.6% in the placebo group, a type I error probability of 0.05, and 80% power.…”

mentioning

confidence: 99%

“…Several observational cohort studies focusing on statin treatment as a preventive effect of AKI have been reported with conflicting results (3,4). Nevertheless, the study results from Billings and colleagues (5) showed that perioperative statin treatment significantly increased the risk of development of AKI following cardiac surgery among statin naïve patients with CKD. The mechanism of harmful effects of de novo statin treatment on renal function is unclear.…”

mentioning

confidence: 99%

No recommendation of routine perioperative statin use for prevention of acute kidney injury in patients undergoing cardiac surgery

2016

View full text Add to dashboard Cite

Acute kidney injury (AKI) develops up to approximately 30% of patients who undergo cardiac surgery (1), and independently associating with increased risk of morbidity and mortality (1,2). The prevention of AKI following cardiac surgery is predominantly important. Statin have been expected to reduce the development of AKI following cardiac surgery based on its anti-inflammatory effects. However, several observational cohort studies focusing on statin treatment as a preventive effect of AKI have been reported with conflicting results (3,4). Retrospective studies might have limitations of inevitable selection bias, and leading into the possibility of misleading and inconclusive results. To date, there is little evidence from randomized trials in populations receiving cardiac surgery to support the role of perioperative statin treatment to prevent AKI.Recently, Billings and colleagues conducted the prospective double-blinded randomized controlled trial of a perioperative statin for prevention of AKI following cardiac surgery (5). Their hypothesis was that perioperative statin would reduce AKI following cardiac surgery by 30% as compared to placebo with an assumed AKI incidence of 27.6% in the placebo group, a type I error probability of 0.05, and 80% power. They enrolled a total of 615 patients (199 naïve to statin treatment and 416 already taking a statin). Enrolled patients were randomized to perioperative statin treatment (80 mg of atorvastatin the day prior surgery, 40 mg of atorvastatin the morning of surgery, and 40 mg of atorvastatin daily following surgery for the duration of hospitalization) or placebo. If patients already taking statin, their pre-enrollment statin was continued until the day of surgery and resumed taking their previously prescribed statin on postoperative day 2 because of ethical issue. The primary endpoint was the incidence of AKI, which was defined as an increase of 0.3 mg/dL in serum creatinine concentration or the initiation of renal replacement therapy within 48 hours of surgery.The data and safety monitoring board recommended stopping the group naïve to statin treatment due to increased AKI among these participants with chronic kidney disease (CKD), defined as an estimated glomerular filtration rate <60 mL/min/1.73 m 2 , receiving atorvastatin. Summary of study results are shown in

show abstract

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

Cited by 203 publications

References 37 publications

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Statins do not prevent cardiac surgery-associated AKI: is ubiquinone the missing link?

No recommendation of routine perioperative statin use for prevention of acute kidney injury in patients undergoing cardiac surgery

Contact Info

Product

Resources

About