Importance Hydroxy-methylglutaryl-coenzyme A reductase inhibitors affect many mechanisms underlying acute kidney injury (AKI). DSMB recommended stopping the statin-na?ve group due to increased AKI among statin-na?ve participants with chronic kidney disease (CKD, estimated glomerular filtration rate <60 ml/min/1.73 m2) receiving atorvastatin and then recommended stopping for futility after 615 participants (median age, 67 years; 188 [30.6%] females, and 202 [32.8%] diabetic) completed the analysis. Among all individuals (n=615), AKI happened in 64 of 308 individuals (20.8%) randomized to atorvastatin versus 60 of 307 individuals (19.5%) randomized to placebo (risk proportion [RR], 1.06 [95% CI, 0.78C1.46]; P=0.75). Among statin-na?ve individuals (n=199), AKI occurred in 22 of 102 (21.6%) receiving atorvastatin versus 13 of 97 (13.4%) receiving placebo (RR, 1.61 [0.86C3.01]; P=0.15), and serum creatinine increased 0.11mg/dl (?0.11 to 0.56) (median [10th to 90th percentile]) in those randomized to atorvastatin versus 0.05 (?0.12 to 0.33) placebo (mean difference, 0.08 mg/dl [95% CI, 0.01C0.15]; P=0.007). Among statin-users (n=416), AKI happened in 42 of 206 (20.4%) randomized to atorvastatin versus 47 of 210 (22.4%) placebo (RR, 0.91 [0.63C1.32]; P=0.63). In CKD sufferers (n=179), AKI happened in 30 of 84 (35.7%) randomized to atorvastatin versus 31 of 95 (32.6%) placebo (RR, 1.09 [0.73C1.65]; P=0.76). In CKD sufferers na?ve to statins (n=36), AKI occurred in 9 of 17 (52.9%) randomized to atorvastatin, versus 3 of 19 (15.8%) placebo (RR, 3.35 [1.12C10.05]; P=0.03), and serum creatinine increased 0.26 (?0.22 to 0.94) versus ?0.06 mg/dl (?0.16 to 0.41) (mean difference, 0.28mg/dl [0.02C0.54]; P=0.04). In CKD Rabbit Polyclonal to CSRL1 statin-users (n=143), AKI happened in 21 of 67 (31.3%) randomized to atorvastatin, versus 28 of 76 (36.8%) placebo (RR, 0.85 [0.54C1.35]; P=0.59). Conclusions and Relevance Among sufferers going through cardiac medical procedures, high-dose perioperative atorvastatin treatment, compared to placebo administration, did not reduce the risk of AKI overall, among patients naive to statins, or patients already using a statin. buy GSK 269962 These results do not support the initiation of statin therapy to prevent AKI following cardiac surgery. Trial Registration Clinicaltrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT00791648″,”term_id”:”NCT00791648″NCT00791648 initiation of perioperative statin treatment in patients na?ve to statins affects AKI, or if statin continuation or perioperative withdrawal in patients already using statins affects buy GSK 269962 AKI. We performed the Statin AKI Cardiac Surgery RCT to test the hypothesis that short-term high-dose perioperative atorvastatin reduces AKI following cardiac surgery. METHODS Study Design and Patients The Statin AKI Cardiac Surgery RCT (“type”:”clinical-trial”,”attrs”:”text”:”NCT00791648″,”term_id”:”NCT00791648″NCT00791648) was an investigator-initiated, double-blinded, placebo-controlled, randomized clinical trial conducted to test the hypothesis that short-term, high-dose, perioperative atorvastatin treatment reduces AKI following cardiac surgery (see buy GSK 269962 Protocol in the Product). Adult patients undergoing elective coronary artery bypass grafting, valvular heart medical procedures, or ascending aortic surgery at Vanderbilt University or college Medical Center (VUMC) were eligible for study participation. Patients with prior statin intolerance; acute coronary syndrome, defined as ST or non-ST elevation myocardial infarction with elevated buy GSK 269962 serum troponin concentrations; liver dysfunction, defined as serum transaminase concentrations greater than three times the upper limit of normal (120 U/L), a bilirubin concentration greater than 3 mg/dl, or a diagnosis of cirrhosis; current use of potent CYP3A4 inhibitors including azole antifungals, protease inhibitors, and macrolide antibiotics; current use of cyclosporine; current renal replacement therapy; history of kidney transplant; a requirement for emergency or urgent medical procedures; or pregnancy were excluded. The analysis was accepted by the Vanderbilt School Institutional Review Plank for Analysis on Human Topics and conducted based on the Declaration of Helsinki. All sufferers provided written up to date consent. Anesthetic, operative, and postoperative administration were conducted regarding to institutional protocols as defined in the Dietary supplement. Involvement Pre-study statin-na?ve sufferers had been randomized to get 80 mg atorvastatin the entire time ahead of.