A Meta-Analysis of Randomized and Observational Studies: Aspirin Protects from Cardiac Surgery-Associated Acute Kidney Injury
Background: Antiplatelet therapy is critical in the management of coronary artery diseases. For patients undergoing cardiac surgeries, including coronary artery bypass graft (CABG) and valve replacement, controversy remains in preoperative antiplatelet therapy concerning risk of bleeding. For safety concern, aspirin is recommended to be withdrawn 5 to 10 days before a cardiac surgery. Recent studies, however, indicate that preoperative aspirin may have a protective effect on cardiac surgery-associated acute kidney injury (CSA-AKI).
Objective: To estimate the efficacy of preoperative aspirin in preventing CSA-AKI.
Methods and results: Eligible studies included randomized controlled trials (RCTs) and observational studies (OSs) of patients, who had undergone CABG, valve replacement, or combined surgery. These studies compared preoperative aspirin with placebo/no aspirin and reported the least incidence of CSA-AKI. One RCT and five OSs met the inclusion criteria. Data retrieved suggested that aspirin prescribed within five days before cardiac surgery decreased post-operative renal failure [odds ratio (OR), 0.67; 95% confidence interval (CI), 0.50-0.89; P < 0.01] and 30-day mortality (OR, 0.64; 95% CI, 0.53-0.77; P < 0.01). One RCT and three OSs suggested aspirin protected from major adverse cardiocerebral events (MACE) (OR, 0.88; 95% CI, 0.76-1.01; P = 0.07). One RCT and two OSs suggested aspirin did not increase risk of re-exploration for bleeding (OR, 1.01; 95% CI, 0.76-1.34; P = 0.95).
Conclusion: Preoperative low-dose aspirin decreases post-operative CSA-AKI, mortality, and MACE without increasing the risk of re-exploration. But most of the studies are observational. They lack a uniformed standard on prescription of aspirin and outcomes measurement. No stratification analysis is performed concerning different types of surgical procedures and comorbidities. More randomized controlled trials are necessary to confirm the efficacy and safety of preoperative aspirin prescription.
Aboul-Hassan SS, Stankowski T, Marczak J, Peksa M, Nawotka M, Stanislawski R, Kryszkowski B, Cichon R. 2017. The use of preoperative aspirin in cardiac surgery: A systematic review and meta-analysis. J Card Surg 32(12):758-774.
Alshaikh HN, Katz NM, Gani F, Nagarajan N, Canner JK, Kacker S, Najjar PA, Higgins RS, Schneider EB. 2017. Financial Impact of Acute Kidney Injury After Cardiac Operations in the United States. ANN THORAC SURG.
Asaduzzaman M, Lavasani S, Rahman M, Zhang S, Braun OO, Jeppsson B, Thorlacius H. 2009. Platelets support pulmonary recruitment of neutrophils in abdominal sepsis. CRIT CARE MED 37(4):1389-1396.
Awtry EH, Loscalzo J. 2000. Aspirin. CIRCULATION 101(10):1206-1218.
Bybee KA, Powell BD, Valeti U, Rosales AG, Kopecky SL, Mullany C, Wright RS. 2005. Preoperative aspirin therapy is associated with improved postoperative outcomes in patients undergoing coronary artery bypass grafting. CIRCULATION 112(9 Suppl): I286-I292.
Cao L, Silvestry S, Zhao N, Diehl J, Sun J. 2012. Effects of preoperative aspirin on cardiocerebral and renal complications in non-emergent cardiac surgery patients: a sub-group and cohort study. PLOS ONE 7(2):e30094.
Cao L, Young N, Liu H, Silvestry S, Sun W, Zhao N, Diehl J, Sun J. 2012. Preoperative aspirin use and outcomes in cardiac surgery patients. ANN SURG 255(2):399-404.
Deng Y, Pisklak PV, Lee VV, Tolpin DA, Collard CD, Elayda MA, Coselli J, Pan W. 2015. Association Between Preoperative Aspirin-dosing Strategy and Mortality After Coronary Artery Bypass Graft Surgery. ANN SURG 262(6):1150-1156.
Dunning J, Versteegh M, Fabbri A, Pavie A, Kolh P, Lockowandt U, Nashef SA. 2008. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardiothorac Surg 34(1):73-92.
Fuhrman DY, Kellum JA. 2017. Epidemiology and pathophysiology of cardiac surgery-associated acute kidney injury. Curr Opin Anaesthesiol 30(1):60-65.
Fuster V, Dyken ML, Vokonas PS, Hennekens C. 1993. Aspirin as a therapeutic agent in cardiovascular disease. Special Writing Group. CIRCULATION 87(2):659-675.
Goldhammer JE, Marhefka GD, Daskalakis C, Berguson MW, Bowen JE, Diehl JT, Sun J. 2015. The Effect of Aspirin on Bleeding and Transfusion in Contemporary Cardiac Surgery. PLOS ONE 10(7):e134670.
Hillis LD, Smith PK, Anderson JL, Bittl JA, Bridges CR, Byrne JG, Cigarroa JE, Disesa VJ, Hiratzka LF, Hutter AJ et al. 2011. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. CIRCULATION 124(23):e652-e735.
Hoste E, Vandenberghe W. 2017. Epidemiology of cardiac surgery-associated acute kidney injury. Best Pract Res Clin Anaesthesiol 31(3):299-303.
Huang J, Donneyong M, Trivedi J, Barnard A, Chaney J, Dotson A, Raymer S, Cheng A, Liu H, Slaughter MS. 2015. Preoperative Aspirin Use and Its Effect on Adverse Events in Patients Undergoing Cardiac Operations. ANN THORAC SURG 99(6):1975-1981.
Hur M, Koo CH, Lee HC, Park SK, Kim M, Kim WH, Kim JT, Bahk JH. 2017. Preoperative aspirin use and acute kidney injury after cardiac surgery: A propensity-score matched observational study. PLOS ONE 12(5):e177201.
Jacob M, Smedira N, Blackstone E, Williams S, Cho L. 2011. Effect of timing of chronic preoperative aspirin discontinuation on morbidity and mortality in coronary artery bypass surgery. CIRCULATION 2011, 123(6):577-583.
Kashani KB, Mao SA, Safadi S, Amiot BP, Glorioso JM, Lieske JC, Nyberg SL, Zhang X. 2017. Association between kidney intracapsular pressure and ultrasound elastography. CRIT CARE 21(1):251.
Kulik A, Ruel M, Jneid H, Ferguson TB, Hiratzka LF, Ikonomidis JS, Lopez-Jimenez F, McNallan SM, Patel M, Roger VL et al. 2015. Secondary prevention after coronary artery bypass graft surgery: a scientific statement from the American Heart Association. CIRCULATION 131(10):927-964.
Levi Y, Sultan A, Alemayehu M, Wall S, Lavi S. 2016. Association of endothelial dysfunction and no-reflow during primary percutaneous coronary intervention for ST-elevation myocardial infarction. Cardiovasc Revasc Med 17(8):552-555.
Lindemann S, Tolley ND, Dixon DA, McIntyre TM, Prescott SM, Zimmerman GA, Weyrich AS. 2001. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J CELL BIOL 154(3):485-490.
Mangano DT. 2002. Aspirin and mortality from coronary bypass surgery. N Engl J Med 347(17):1309-1317.
Mazzeffi M, Galvagno S, Gammie JS, Tanaka K. 2016. Impact of aspirin use on morbidity and mortality in massively transfused cardiac surgery patients: a propensity score matched cohort study. J ANESTH 30(5):817-825.
Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussieres JS et al. 2016. Stopping vs. Continuing Aspirin before Coronary Artery Surgery. N Engl J Med 374(8):728-737.
Myles PS, Smith J, Knight J, Cooper DJ, Silbert B, McNeil J, Esmore DS, Buxton B, Krum H, Forbes A et al. 2008. Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) Trial: rationale and design. AM HEART J 155(2):224-230.
Nilsson L, Brunnkvist S, Nilsson U, Nystrom SO, Tyden H, Venge P, Aberg T. 1988. Activation of inflammatory systems during cardiopulmonary bypass. Scand J Thorac Cardiovasc Surg 22(1):51-53.
Rosner MH, Okusa MD. 2006. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 1(1):19-32.
Shin SR, Kim WH, Kim DJ, Shin IW, Sohn JT. 2016. Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery. BIOMED RES INT 2016:2985148.
Smith TL, Weyrich AS. 2011. Platelets as central mediators of systemic inflammatory responses. THROMB RES 127(5):391-394.
Sun JC, Whitlock R, Cheng J, Eikelboom JW, Thabane L, Crowther MA, Teoh KH. 2008. The effect of pre-operative aspirin on bleeding, transfusion, myocardial infarction, and mortality in coronary artery bypass surgery: a systematic review of randomized and observational studies. EUR HEART J 29(8):1057-1071.
Toner P, McAuley DF, Shyamsundar M. 2015. Aspirin as a potential treatment in sepsis or acute respiratory distress syndrome. CRIT CARE 19:374.
Wang Y, Bellomo R. 2017. Cardiac surgery-associated acute kidney injury: risk factors, pathophysiology and treatment. NAT REV NEPHROL 13(11):697-711.
Weissmann G, Montesinos MC, Pillinger M, Cronstein BN. 2002. Non-prostaglandin effects of aspirin III and salicylate: inhibition of integrin-dependent human neutrophil aggregation and inflammation in COX 2- and NF kappa B (P105)-knockout mice. ADV EXP MED BIOL 507:571-577.
Xiao F, Wu H, Sun H, Pan S, Xu J, Song Y. 2015. Effect of preoperatively continued aspirin use on early and mid-term outcomes in off-pump coronary bypass surgery: a propensity score-matched study of 1418 patients. PLOS ONE 10(2):e116311.
Yao L, Young N, Liu H, Li Z, Sun W, Goldhammer J, Tao L, He J, Diehl J, Sun J. 2015. Evidence for preoperative aspirin improving major outcomes in patients with chronic kidney disease undergoing cardiac surgery: a cohort study. ANN SURG 261(1):207-212.
Yoshimura Y, Hiramatsu Y, Sato Y, Homma S, Enomoto Y, Kikuchi Y, Sakakibara Y. 2003. Activated neutrophils and platelet microaggregates impede blood filterability through microchannels during simulated extracorporeal circulation. ANN THORAC SURG 75(4):1254-1260.