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Perioperative Statins in Cardiac Surgery and Acute Kidney Injury

Perioperative Statins in Cardiac Surgery and Acute Kidney Injury Long-term statin therapy is common among patients and is particularly common among patients who undergo cardiac surgery.1 Among patients undergoing cardiac surgery, perioperative statin therapy is considered desirable because it has been associated with favorable outcomes, such as decreased level of C-reactive protein, lower incidence of atrial fibrillation, and shorter length of hospital stay.2-5 Moreover, such off-label prescribing of statins is indirectly supported by knowledge of their pleiotropic anti-inflammatory effects.6 These effects of statins make any beneficial clinical effect biologically plausible in situations for which activation of the inflammatory pathways is prominent. Accordingly, the combination of such potentially relevant beneficial effects of statins in diseases associated with inflammation and the wide availability, safety, low cost, excellent absorption, and ease of administration of statins have led clinicians to investigate statin treatment for patients with inflammatory states as diverse as sepsis, acute respiratory distress syndrome (ARDS), and cardiac surgery. Such investigations of statins have mostly relied on observational studies, often involving thousands of patients and appropriately adjusting for baseline characteristics in an attempt to discern a specific independent association.7 However, such studies inevitably carry a risk of selection, publication, and ascertainment bias. Specifically, any adjustments for baseline characteristics cannot control for the many confounders not available or unknown to investigators. Yet, in this setting, the search for a new simple, safe, and inexpensive generic adjuvant intervention for conditions for which no such treatment exists may lead clinicians toward a state of hopeful optimism and away from the cautious skepticism that such observational studies should normally generate. Researchers, however, know that data from observational studies can be misleading and have seen the clear need for randomized clinical trials (RCTs). To date, there have been 3 multicenter RCTs involving statin therapy for the inflammatory states associated with sepsis and ARDS,8-10 and the results have not been supportive. Moreover, in the largest trial involving patients with ARDS, rosuvastatin therapy was associated with fewer days free of renal failure.10 These treatment failures in patients with other inflammatory states have not affected the potential that for patients undergoing cardiac surgery and other major operations, the renal effects would be different, a stance, once again, supported by a significant body of observational data that suggested statins may exert a beneficial effect on kidney function.4,11-13 This issue matters because acute kidney injury (AKI) associated with cardiac surgery is an important condition with a likely inflammatory component that affects up to 30% of patients undergoing major cardiac procedures14; is the second most common trigger of AKI in patients treated in the intensive care unit in developed countries15; and is associated with significant morbidity and mortality and yet has no specific therapy. It is in this context that the study in this issue of JAMA by Billings et al16 represents a major step forward. These investigators reported results from the first large double-blind RCT of a statin (high-dose atorvastatin) for prevention of AKI during cardiac surgery among 199 patients naive to statin treatment and 416 patients already taking a statin.16 The findings have clinical implications. The component of the study involving patients naive to statin treatment was stopped by the data and safety monitoring board (DSMB) because of concerns related to increased AKI incidence among patients naive to statin treatment with chronic kidney disease (CKD); and the entire study was later stopped on the grounds of futility. Among patients naive to statin treatment (n = 199), the overall point estimate for the relative risk [RR] to develop AKI was 1.61. Among patients naive to statin treatment with preoperative CKD, the overall point estimate for the relative risk to develop AKI was 3.35. Overall, AKI developed in 64 of 308 patients in the atorvastatin group vs 60 of 307 patients in the placebo group (RR, 1.06; 95% CI, 0.78-1.46). Among patients naive to statin treatment, AKI occurred in 22 of 102 in the atorvastatin group vs 13 of 97 in the placebo group (RR, 1.61; 95% CI, 0.86-3.01). Among patients naive to statin treatment with CKD (n = 36), AKI occurred in 9 of 17 (52.9%) in the atorvastatin group vs 3 of 19 (15.8%) in the placebo group. Moreover, in both subgroups there was a significant difference in the increase of median serum creatinine concentration that was greater in the patients who received atorvastatin. In contrast, no such effect was seen in patients already taking a statin prior to study enrollment among whom the overall point estimate for AKI was 0.91 and was 0.85 among those with CKD. 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. 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. In the absence of any other convincing evidence of benefit, these findings strongly argue in favor of not administering statins to patients naive to statin treatment about to undergo cardiac surgery. The trial by Billings et al16 also has some limitations. First, the study was conducted at a single center, thus potentially increasing internal validity but decreasing external validity. Second, the authors used the Acute Kidney Injury Network criteria for the definition of AKI but did not account for urinary output. Third, data beyond the first 48 hours after surgery were not reported. Fourth, the trial was not powered to detect patient-centered outcomes such as the need for renal replacement therapy. Fifth, most of the episodes of AKI were mild and of uncertain clinical meaning. Sixth, given the small number of events among patients with CKD, some of the findings may represent type I error. Despite these limitations, this RCT has several important features of a high-quality study (randomization, allocation concealment, detailed baseline data, double blinding, independent monitoring, predefined outcome measures, additional sensitivity and propensity analyses) that make the evidence obtained likely free of biases and confounders and vastly superior to any associative data reported so far. Moreover, these conclusions of no effect are supported by other studies17-20 that have been reported since the start of the study (approximately 5 years ago), implying that the probability a kidney-protective benefit might exist from administering perioperative statins to patients naive to statin treatment undergoing cardiac surgery must be negligible. Even though the use of statins in cardiac surgery is likely to continue to generate interest and trials in an attempt to demonstrate other so-far unproven benefits,21 any use as nephroprotective agents in patients naive to statin treatment undergoing cardiac surgery should now be abandoned. The challenge of finding an adjuvant intervention capable of attenuating AKI during cardiac surgery, however, remains unmet22 and 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. Editorials represent the opinions of the authors and JAMA and not those of the American Medical Association. Back to top Article Information Corresponding Author: Rinaldo Bellomo, MBBS(Hons), MD, FRACP, FCICM, School of Medicine, University of Melbourne, 145 Studley Rd, Heidelberg, Victoria, Australia 3084 (rinaldo.bellomo@austin.org.au). Published Online: February 23, 2016. doi:10.1001/jama.2016.0245. Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. References 1. Wang J, Gu C, Gao M, Yu W, Yu Y. Preoperative statin therapy and renal outcomes after cardiac surgery: a meta-analysis and meta-regression of 59,771 patients. Can J Cardiol. 2015;31(8):1051-1060.PubMedGoogle ScholarCrossref 2. Xia J, Qu Y, Yin C, Xu D. Preoperative rosuvastatin protects patients with coronary artery disease undergoing noncardiac surgery. Cardiology. 2015;131(1):30-37.PubMedGoogle ScholarCrossref 3. Liakopoulos OJ, Kuhn EW, Slottosch I, Wassmer G, Wahlers T. Preoperative statin therapy for patients undergoing cardiac surgery. Cochrane Database Syst Rev. 2012;4:CD008493.PubMedGoogle Scholar 4. Molnar AO, Parikh CR, Coca SG, et al; TRIBE-AKI Consortium. Association between preoperative statin use and acute kidney injury biomarkers in cardiac surgical procedures. Ann Thorac Surg. 2014;97(6):2081-2087.PubMedGoogle ScholarCrossref 5. Patti G, Chello M, Candura D, et al. Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After Cardiac Surgery) study. Circulation. 2006;114(14):1455-1461.PubMedGoogle ScholarCrossref 6. Sodha NR, Sellke FW. The effect of statins on perioperative inflammation in cardiac and thoracic surgery. J Thorac Cardiovasc Surg. 2015;149(6):1495-1501.PubMedGoogle ScholarCrossref 7. McIlroy DR, Myles PS. Does the use of statins improve outcomes in coronary artery bypass graft surgery? Expert Rev Cardiovasc Ther. 2015;13(12):1285-1288.PubMedGoogle ScholarCrossref 8. Kruger P, Bailey M, Bellomo R, et al; ANZ-STATInS Investigators–ANZICS Clinical Trials Group. A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. Am J Respir Crit Care Med. 2013;187(7):743-750.PubMedGoogle ScholarCrossref 9. McAuley DF, Laffey JG, O’Kane CM, et al; HARP-2 Investigators; Irish Critical Care Trials Group. Simvastatin in the acute respiratory distress syndrome. N Engl J Med. 2014;371(18):1695-1703.PubMedGoogle ScholarCrossref 10. Truwit JD, Bernard GR, Steingrub J, et al; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014;370(23):2191-2200.PubMedGoogle ScholarCrossref 11. Molnar AO, Coca SG, Devereaux PJ, et al. Statin use associates with a lower incidence of acute kidney injury after major elective surgery. J Am Soc Nephrol. 2011;22(5):939-946.PubMedGoogle ScholarCrossref 12. Wang J, Gu C, Gao M, Yu W, Yu Y. Preoperative statin therapy and renal outcomes after cardiac surgery: a meta-analysis and meta-regression of 59,771 patients. Can J Cardiol. 2015;31(8):1051-1060.PubMedGoogle ScholarCrossref 13. Brunelli SM, Waikar SS, Bateman BT, et al. Preoperative statin use and postoperative acute kidney injury. Am J Med. 2012;125(12):1195-1204.e3.PubMedGoogle ScholarCrossref 14. Bellomo R, Auriemma S, Fabbri A, et al. The pathophysiology of cardiac surgery-associated acute kidney injury (CSA-AKI). Int J Artif Organs. 2008;31(2):166-178.PubMedGoogle Scholar 15. Uchino S, Kellum JA, Bellomo R, et al; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813-818.PubMedGoogle ScholarCrossref 16. Billings FT, Hendricks PA, Schildcrout JS, et al. High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial. JAMA. doi:10.1001/jama.2016.0548.Google Scholar 17. Kuhn EW, Slottosch I, Wahlers T, Liakopoulos OJ. Preoperative statin therapy for patients undergoing cardiac surgery. Cochrane Database Syst Rev. 2015;8:CD008493.PubMedGoogle Scholar 18. Lewicki M, Ng I, Schneider AG. HMG CoA reductase inhibitors (statins) for preventing acute kidney injury after surgical procedures requiring cardiac bypass. Cochrane Database Syst Rev. 2015;3:CD010480.PubMedGoogle Scholar 19. Prowle JR, Calzavacca P, Licari E, et al. Pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery. Nephrology (Carlton). 2012;17(3):215-224.PubMedGoogle ScholarCrossref 20. Dormuth CR, Hemmelgarn BR, Paterson JM, et al; Canadian Network for Observational Drug Effect Studies. Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ. 2013;346:f880.PubMedGoogle ScholarCrossref 21. Liakopoulos OJ, Kuhn EW, Hellmich M, et al; StaRT-CABG Investigators. Statin Recapture Therapy before Coronary Artery Bypass Grafting Trial: rationale and study design of a multicenter, randomized, double-blinded controlled clinical trial. Am Heart J. 2015;170(1):46-54, 54.e1-54.e2.PubMedGoogle ScholarCrossref 22. Bove T, Zangrillo A, Guarracino F, et al. Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial. JAMA. 2014;312(21):2244-2253.PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Perioperative Statins in Cardiac Surgery and Acute Kidney Injury

JAMA , Volume 315 (9) – Mar 1, 2016

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References (20)

Publisher
American Medical Association
Copyright
Copyright © 2016 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2016.0245
Publisher site
See Article on Publisher Site

Abstract

Long-term statin therapy is common among patients and is particularly common among patients who undergo cardiac surgery.1 Among patients undergoing cardiac surgery, perioperative statin therapy is considered desirable because it has been associated with favorable outcomes, such as decreased level of C-reactive protein, lower incidence of atrial fibrillation, and shorter length of hospital stay.2-5 Moreover, such off-label prescribing of statins is indirectly supported by knowledge of their pleiotropic anti-inflammatory effects.6 These effects of statins make any beneficial clinical effect biologically plausible in situations for which activation of the inflammatory pathways is prominent. Accordingly, the combination of such potentially relevant beneficial effects of statins in diseases associated with inflammation and the wide availability, safety, low cost, excellent absorption, and ease of administration of statins have led clinicians to investigate statin treatment for patients with inflammatory states as diverse as sepsis, acute respiratory distress syndrome (ARDS), and cardiac surgery. Such investigations of statins have mostly relied on observational studies, often involving thousands of patients and appropriately adjusting for baseline characteristics in an attempt to discern a specific independent association.7 However, such studies inevitably carry a risk of selection, publication, and ascertainment bias. Specifically, any adjustments for baseline characteristics cannot control for the many confounders not available or unknown to investigators. Yet, in this setting, the search for a new simple, safe, and inexpensive generic adjuvant intervention for conditions for which no such treatment exists may lead clinicians toward a state of hopeful optimism and away from the cautious skepticism that such observational studies should normally generate. Researchers, however, know that data from observational studies can be misleading and have seen the clear need for randomized clinical trials (RCTs). To date, there have been 3 multicenter RCTs involving statin therapy for the inflammatory states associated with sepsis and ARDS,8-10 and the results have not been supportive. Moreover, in the largest trial involving patients with ARDS, rosuvastatin therapy was associated with fewer days free of renal failure.10 These treatment failures in patients with other inflammatory states have not affected the potential that for patients undergoing cardiac surgery and other major operations, the renal effects would be different, a stance, once again, supported by a significant body of observational data that suggested statins may exert a beneficial effect on kidney function.4,11-13 This issue matters because acute kidney injury (AKI) associated with cardiac surgery is an important condition with a likely inflammatory component that affects up to 30% of patients undergoing major cardiac procedures14; is the second most common trigger of AKI in patients treated in the intensive care unit in developed countries15; and is associated with significant morbidity and mortality and yet has no specific therapy. It is in this context that the study in this issue of JAMA by Billings et al16 represents a major step forward. These investigators reported results from the first large double-blind RCT of a statin (high-dose atorvastatin) for prevention of AKI during cardiac surgery among 199 patients naive to statin treatment and 416 patients already taking a statin.16 The findings have clinical implications. The component of the study involving patients naive to statin treatment was stopped by the data and safety monitoring board (DSMB) because of concerns related to increased AKI incidence among patients naive to statin treatment with chronic kidney disease (CKD); and the entire study was later stopped on the grounds of futility. Among patients naive to statin treatment (n = 199), the overall point estimate for the relative risk [RR] to develop AKI was 1.61. Among patients naive to statin treatment with preoperative CKD, the overall point estimate for the relative risk to develop AKI was 3.35. Overall, AKI developed in 64 of 308 patients in the atorvastatin group vs 60 of 307 patients in the placebo group (RR, 1.06; 95% CI, 0.78-1.46). Among patients naive to statin treatment, AKI occurred in 22 of 102 in the atorvastatin group vs 13 of 97 in the placebo group (RR, 1.61; 95% CI, 0.86-3.01). Among patients naive to statin treatment with CKD (n = 36), AKI occurred in 9 of 17 (52.9%) in the atorvastatin group vs 3 of 19 (15.8%) in the placebo group. Moreover, in both subgroups there was a significant difference in the increase of median serum creatinine concentration that was greater in the patients who received atorvastatin. In contrast, no such effect was seen in patients already taking a statin prior to study enrollment among whom the overall point estimate for AKI was 0.91 and was 0.85 among those with CKD. 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. 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. In the absence of any other convincing evidence of benefit, these findings strongly argue in favor of not administering statins to patients naive to statin treatment about to undergo cardiac surgery. The trial by Billings et al16 also has some limitations. First, the study was conducted at a single center, thus potentially increasing internal validity but decreasing external validity. Second, the authors used the Acute Kidney Injury Network criteria for the definition of AKI but did not account for urinary output. Third, data beyond the first 48 hours after surgery were not reported. Fourth, the trial was not powered to detect patient-centered outcomes such as the need for renal replacement therapy. Fifth, most of the episodes of AKI were mild and of uncertain clinical meaning. Sixth, given the small number of events among patients with CKD, some of the findings may represent type I error. Despite these limitations, this RCT has several important features of a high-quality study (randomization, allocation concealment, detailed baseline data, double blinding, independent monitoring, predefined outcome measures, additional sensitivity and propensity analyses) that make the evidence obtained likely free of biases and confounders and vastly superior to any associative data reported so far. Moreover, these conclusions of no effect are supported by other studies17-20 that have been reported since the start of the study (approximately 5 years ago), implying that the probability a kidney-protective benefit might exist from administering perioperative statins to patients naive to statin treatment undergoing cardiac surgery must be negligible. Even though the use of statins in cardiac surgery is likely to continue to generate interest and trials in an attempt to demonstrate other so-far unproven benefits,21 any use as nephroprotective agents in patients naive to statin treatment undergoing cardiac surgery should now be abandoned. The challenge of finding an adjuvant intervention capable of attenuating AKI during cardiac surgery, however, remains unmet22 and 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. Editorials represent the opinions of the authors and JAMA and not those of the American Medical Association. Back to top Article Information Corresponding Author: Rinaldo Bellomo, MBBS(Hons), MD, FRACP, FCICM, School of Medicine, University of Melbourne, 145 Studley Rd, Heidelberg, Victoria, Australia 3084 (rinaldo.bellomo@austin.org.au). Published Online: February 23, 2016. doi:10.1001/jama.2016.0245. Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. References 1. Wang J, Gu C, Gao M, Yu W, Yu Y. Preoperative statin therapy and renal outcomes after cardiac surgery: a meta-analysis and meta-regression of 59,771 patients. Can J Cardiol. 2015;31(8):1051-1060.PubMedGoogle ScholarCrossref 2. Xia J, Qu Y, Yin C, Xu D. Preoperative rosuvastatin protects patients with coronary artery disease undergoing noncardiac surgery. Cardiology. 2015;131(1):30-37.PubMedGoogle ScholarCrossref 3. Liakopoulos OJ, Kuhn EW, Slottosch I, Wassmer G, Wahlers T. Preoperative statin therapy for patients undergoing cardiac surgery. Cochrane Database Syst Rev. 2012;4:CD008493.PubMedGoogle Scholar 4. Molnar AO, Parikh CR, Coca SG, et al; TRIBE-AKI Consortium. Association between preoperative statin use and acute kidney injury biomarkers in cardiac surgical procedures. Ann Thorac Surg. 2014;97(6):2081-2087.PubMedGoogle ScholarCrossref 5. Patti G, Chello M, Candura D, et al. Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After Cardiac Surgery) study. Circulation. 2006;114(14):1455-1461.PubMedGoogle ScholarCrossref 6. Sodha NR, Sellke FW. The effect of statins on perioperative inflammation in cardiac and thoracic surgery. J Thorac Cardiovasc Surg. 2015;149(6):1495-1501.PubMedGoogle ScholarCrossref 7. McIlroy DR, Myles PS. Does the use of statins improve outcomes in coronary artery bypass graft surgery? Expert Rev Cardiovasc Ther. 2015;13(12):1285-1288.PubMedGoogle ScholarCrossref 8. Kruger P, Bailey M, Bellomo R, et al; ANZ-STATInS Investigators–ANZICS Clinical Trials Group. A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. Am J Respir Crit Care Med. 2013;187(7):743-750.PubMedGoogle ScholarCrossref 9. McAuley DF, Laffey JG, O’Kane CM, et al; HARP-2 Investigators; Irish Critical Care Trials Group. Simvastatin in the acute respiratory distress syndrome. N Engl J Med. 2014;371(18):1695-1703.PubMedGoogle ScholarCrossref 10. Truwit JD, Bernard GR, Steingrub J, et al; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014;370(23):2191-2200.PubMedGoogle ScholarCrossref 11. Molnar AO, Coca SG, Devereaux PJ, et al. Statin use associates with a lower incidence of acute kidney injury after major elective surgery. J Am Soc Nephrol. 2011;22(5):939-946.PubMedGoogle ScholarCrossref 12. Wang J, Gu C, Gao M, Yu W, Yu Y. Preoperative statin therapy and renal outcomes after cardiac surgery: a meta-analysis and meta-regression of 59,771 patients. Can J Cardiol. 2015;31(8):1051-1060.PubMedGoogle ScholarCrossref 13. Brunelli SM, Waikar SS, Bateman BT, et al. Preoperative statin use and postoperative acute kidney injury. Am J Med. 2012;125(12):1195-1204.e3.PubMedGoogle ScholarCrossref 14. Bellomo R, Auriemma S, Fabbri A, et al. The pathophysiology of cardiac surgery-associated acute kidney injury (CSA-AKI). Int J Artif Organs. 2008;31(2):166-178.PubMedGoogle Scholar 15. Uchino S, Kellum JA, Bellomo R, et al; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813-818.PubMedGoogle ScholarCrossref 16. Billings FT, Hendricks PA, Schildcrout JS, et al. High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial. JAMA. doi:10.1001/jama.2016.0548.Google Scholar 17. Kuhn EW, Slottosch I, Wahlers T, Liakopoulos OJ. Preoperative statin therapy for patients undergoing cardiac surgery. Cochrane Database Syst Rev. 2015;8:CD008493.PubMedGoogle Scholar 18. Lewicki M, Ng I, Schneider AG. HMG CoA reductase inhibitors (statins) for preventing acute kidney injury after surgical procedures requiring cardiac bypass. Cochrane Database Syst Rev. 2015;3:CD010480.PubMedGoogle Scholar 19. Prowle JR, Calzavacca P, Licari E, et al. Pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery. Nephrology (Carlton). 2012;17(3):215-224.PubMedGoogle ScholarCrossref 20. Dormuth CR, Hemmelgarn BR, Paterson JM, et al; Canadian Network for Observational Drug Effect Studies. Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ. 2013;346:f880.PubMedGoogle ScholarCrossref 21. Liakopoulos OJ, Kuhn EW, Hellmich M, et al; StaRT-CABG Investigators. Statin Recapture Therapy before Coronary Artery Bypass Grafting Trial: rationale and study design of a multicenter, randomized, double-blinded controlled clinical trial. Am Heart J. 2015;170(1):46-54, 54.e1-54.e2.PubMedGoogle ScholarCrossref 22. Bove T, Zangrillo A, Guarracino F, et al. Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial. JAMA. 2014;312(21):2244-2253.PubMedGoogle ScholarCrossref

Journal

JAMAAmerican Medical Association

Published: Mar 1, 2016

Keywords: coronary artery bypass surgery,statins,cardiac surgery procedures,renal failure, acute,perioperative care,postoperative renal failure,sharp trial,heart valve surgery

There are no references for this article.