High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.
High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.
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DOI：
10.1001/jama.2016.0548
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
Brown NJ
中科院分区：
文献类型：
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作者：
Billings FT 4th;Hendricks PA;Schildcrout JS;Shi Y;Petracek MR;Byrne JG;Brown NJ
羟甲基戊二酰辅酶A还原酶抑制剂影响急性肾损伤(AKI)的几种机制。为了验证短期大剂量阿托伐他汀可以减少心脏手术后AKI的假设，2009年11月至2014年10月在范德比尔特大学医学中心进行的成人心脏手术患者的双盲、安慰剂对照、随机试验。他汀类药物单纯的患者(n=199)被随机分配到手术前一天80 mg、手术当天早上40 mg和手术后每天40 mg(n=102)或匹配的安慰剂(n=97)。在研究登记前使用他汀类药物的患者(n=416)继续进行他汀类药物治疗，直到手术当天，随机分配手术当天早上80 mg阿托伐他汀和手术后第二天早上40 mg阿托伐他汀(n=206)或匹配的安慰剂(n=210)，并在术后第2天恢复他汀类药物治疗。AKI，定义为术后48小时内血清肌酐升高0.3 mg/dl(类似标准)，DSMB建议停止服用他汀类药物组，原因是他汀类药物初治的慢性肾脏疾病(CKD)患者的AKI增加，估计肾小球滤过率和肾小球滤过率；60ml/min/1.73m2)，然后建议在615名参与者(中位年龄67岁；188名(30.6%)女性和202名[32.8%]糖尿病患者)完成研究后停药。在所有参与者(n=615)中，308名随机服用阿托伐他汀的参与者(20.8%)发生急性心肌梗死，而307名随机服用安慰剂的参与者中有60名(19.5%)发生急性心肌梗死(风险比[RR]，1.06[95%CI，0.78-1.46]；P=0.75)。在未服用他汀类药物的受试者中(n=199)，服用阿托伐他汀的102人中有22人(21.6%)发生急性心肌梗死，而服用安慰剂的97人中有13人(13.4%)发生急性心肌梗死(RR，1.61[0.86-3.01]；P=0.15)，随机服用阿托伐他汀的患者血清肌酐升高0.11 mg/dl(−为0.11至0.56)(中位数为[第10至90百分位数])，而服用安慰剂的患者为0.05(−为0.12至0.33)(平均差异为0.08 mg/dl[95%CI，0.01-0.15]；P=0.007)。在他汀类药物使用者(n=416)中，随机服用阿托伐他汀的206人中有42人(20.4%)发生AKI，而服用安慰剂的210人中有47人(22.4%)发生AKI(RR，0.91[0.63-1.32]；P=0.63)。在CKD患者(n=179)中，84名随机服用阿托伐他汀的患者中有30名(35.7%)发生AKI，而95名安慰剂组中有31名(32.6%)发生AKI(RR，1.09[0.73-1.65]；P=0.76)。在单纯服用他汀类药物的慢性肾脏病患者(n=36)中，随机服用阿托伐他汀的17名患者中有9名(52.9%)发生急性心肌梗死，而服用安慰剂的19名患者中有3名(15.8%)发生急性心肌梗死(RR，3.35[1.12-10.05]；P=0.03)；血清肌酐增加0.26(−0.22~0.94)，−0.06 mg/dl(−0.16~0.41)(平均差异0.28 mg/dl[0.02~0.54]；P=0.04)。在CKD他汀类药物使用者(n=143)中，67名随机服用阿托伐他汀的患者中有21名(31.3%)发生AKI，而76名安慰剂组中有28名(36.8%)发生AKI(RR，0.85[0.54-1.35]；P=0.59)。在接受心脏手术的患者中，与安慰剂治疗相比，围手术期大剂量阿托伐他汀治疗并不能总体上降低AKI的风险，对于单纯使用他汀类药物的患者或已经使用他汀类药物的患者来说。这些结果并不支持心脏手术后开始应用他汀类药物来预防AKI。ClinicalTrials.gov标识：NCT00791648
Hydroxy-methylglutaryl-coenzyme A reductase inhibitors affect several mechanisms underlying acute kidney injury (AKI). To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery Double-blinded, placebo-controlled, randomized trial of adult cardiac surgery patients conducted November 2009 to October 2014 at Vanderbilt University Medical Center Statin-naïve patients (n=199) were randomly assigned 80mg atorvastatin the day before surgery, 40mg the morning of surgery, and 40mg daily following surgery (n=102) or matching placebo (n=97). Patients using statins prior to study enrollment (n=416) continued their pre-enrollment statin until the day of surgery, were randomly assigned 80mg atorvastatin the morning of surgery and 40mg the morning after (n=206) or matching placebo (n=210), and resumed their statin on postoperative day 2. AKI, defined as 0.3 mg/dl rise in serum creatinine within 48 hours of surgery (AKIN criteria) The DSMB recommended stopping the statin-naïve group due to increased AKI among statin-naïve 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%] women, and 202 [32.8%] diabetic) completed the study. Among all participants (n=615), AKI occurred in 64 of 308 participants (20.8%) randomized to atorvastatin versus 60 of 307 participants (19.5%) randomized to placebo (risk ratio [RR], 1.06 [95% CI, 0.78–1.46]; P=0.75). Among statin-naïve participants (n=199), AKI occurred in 22 of 102 (21.6%) receiving atorvastatin versus 13 of 97 (13.4%) receiving placebo (RR, 1.61 [0.86–3.01]; 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, 0.01–0.15]; P=0.007). Among statin-users (n=416), AKI occurred in 42 of 206 (20.4%) randomized to atorvastatin versus 47 of 210 (22.4%) placebo (RR, 0.91 [0.63–1.32]; P=0.63). In CKD patients (n=179), AKI occurred in 30 of 84 (35.7%) randomized to atorvastatin versus 31 of 95 (32.6%) placebo (RR, 1.09 [0.73–1.65]; P=0.76). In CKD patients naïve 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 [1.12–10.05]; 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 [0.02–0.54]; P=0.04). In CKD statin-users (n=143), AKI occurred in 21 of 67 (31.3%) randomized to atorvastatin, versus 28 of 76 (36.8%) placebo (RR, 0.85 [0.54–1.35]; P=0.59). Among patients undergoing cardiac surgery, 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. These results do not support the initiation of statin therapy to prevent AKI following cardiac surgery. Clinicaltrials.gov identifier: NCT00791648