Perioperative statin therapy in patients at high risk for cardiovascular morbidity undergoing surgery: a review
2014; Elsevier BV; Volume: 114; Issue: 1 Linguagem: Inglês
10.1093/bja/aeu295
ISSN1471-6771
AutoresB. A. de Waal, Marc P. Buise, André van Zundert,
Tópico(s)Aortic aneurysm repair treatments
ResumoSummaryStatins feature documented benefits for primary and secondary prevention of cardiovascular disease and are thought to improve perioperative outcomes in patients undergoing surgery. To assess the clinical outcomes of perioperative statin treatment in statin-naive patients undergoing surgery, a systematic review was performed. Studies were included if they met the following criteria: randomized controlled trials, patients aged ≥18 yr undergoing surgery, patients not already on long-term statin treatment, reported outcomes including at least one of the following: mortality, myocardial infarction, atrial fibrillation, stroke, and length of hospital stay. The following randomized clinical trials were excluded: retrospective studies, trials without surgical procedure, trials without an outcome of interest, studies with patients on statin therapy before operation, or papers not written in English. The literature search revealed 16 randomized controlled studies involving 2275 patients. Pooled results showed a significant reduction in (i) mortality [risk ratio (RR) 0.53, 95% confidence interval (CI) 0.30–0.94, P=0.03], (ii) myocardial infarction (RR 0.54, 95% CI 0.38–0.76, P<0.001), (iii) perioperative atrial fibrillation (RR 0.53, 95% CI 0.43–0.66, P<0.001), and (iv) length of hospital stay (days, mean difference −0.58, 95% CI −0.79 to −0.37, P<0.001) in patients treated with a statin. Subgroup analysis in patients undergoing non-cardiac surgery showed a decrease in the perioperative incidence of mortality and myocardial infarction. Consequently, anaesthetists should consider prescribing a standard-dose statin before operation to statin-naive patients undergoing cardiac surgery. However, there are insufficient data to support final recommendations on perioperative statin therapy for patients undergoing non-cardiac surgery. Statins feature documented benefits for primary and secondary prevention of cardiovascular disease and are thought to improve perioperative outcomes in patients undergoing surgery. To assess the clinical outcomes of perioperative statin treatment in statin-naive patients undergoing surgery, a systematic review was performed. Studies were included if they met the following criteria: randomized controlled trials, patients aged ≥18 yr undergoing surgery, patients not already on long-term statin treatment, reported outcomes including at least one of the following: mortality, myocardial infarction, atrial fibrillation, stroke, and length of hospital stay. The following randomized clinical trials were excluded: retrospective studies, trials without surgical procedure, trials without an outcome of interest, studies with patients on statin therapy before operation, or papers not written in English. The literature search revealed 16 randomized controlled studies involving 2275 patients. Pooled results showed a significant reduction in (i) mortality [risk ratio (RR) 0.53, 95% confidence interval (CI) 0.30–0.94, P=0.03], (ii) myocardial infarction (RR 0.54, 95% CI 0.38–0.76, P<0.001), (iii) perioperative atrial fibrillation (RR 0.53, 95% CI 0.43–0.66, P<0.001), and (iv) length of hospital stay (days, mean difference −0.58, 95% CI −0.79 to −0.37, P<0.001) in patients treated with a statin. Subgroup analysis in patients undergoing non-cardiac surgery showed a decrease in the perioperative incidence of mortality and myocardial infarction. Consequently, anaesthetists should consider prescribing a standard-dose statin before operation to statin-naive patients undergoing cardiac surgery. However, there are insufficient data to support final recommendations on perioperative statin therapy for patients undergoing non-cardiac surgery. Editor's key points•The authors review the evidence of improved operative outcome in the use of statins in statin-naive patients.•They found clear reductions in mortality and myocardial infarct.•Outcomes appeared most improved in patients undergoing cardiac surgery, but were also apparent in non-cardiac surgery. •The authors review the evidence of improved operative outcome in the use of statins in statin-naive patients.•They found clear reductions in mortality and myocardial infarct.•Outcomes appeared most improved in patients undergoing cardiac surgery, but were also apparent in non-cardiac surgery. The benefits of perioperative statins in intermediate- or high-risk patients undergoing surgery are not clear. In large randomized trials, statins feature documented benefits for primary and secondary prevention of cardiovascular disease and subsequently decreased morbidity and mortality due to cardiovascular events.1Skrlin S Hou V A review of perioperative statin therapy for noncardiac surgery.Semin Cardiothorac Vasc Anesth. 2010; 14: 283-290Crossref PubMed Scopus (16) Google Scholar, 2Golomb BA Evans MA Statin adverse effects: a review of the literature and evidence for a mitochondrial mechanism.Am J Cardiovasc Drugs. 2008; 8: 373-418Crossref PubMed Scopus (527) Google Scholar, 3Lindenauer PK Pekow P Wang K Gutierrez B Benjamin EM Lipid-lowering therapy and in-hospital mortality following major noncardiac surgery.J Am Med Assoc. 2004; 291: 2092-2099Crossref PubMed Scopus (371) Google Scholar Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are pharmaceutical agents that competitively inhibit the enzymatic activity of HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis. This leads to decreased hepatic cholesterol synthesis, up-regulation of low-density lipoprotein (LDL) receptor, and increased clearance of plasma LDL cholesterol.4Zhou Q Liao JK Pleiotropic effects of statins.Circ J. 2010; 74: 818-826Crossref PubMed Scopus (454) Google Scholar HMG-CoA reductase inhibitors also reduce plasma triglycerides and they have a modest high-density lipoprotein (HDL) cholesterol-raising effect. The full therapeutic effect is obtained by 4–6 weeks, with at least 75% of the ultimate effect apparent by 2 weeks after starting therapy.5Illingworth DR Tobert JA HMG-CoA reductase inhibitors.Adv Protein Chem. 2001; 56: 77-114Crossref PubMed Scopus (36) Google Scholar Besides decreasing cholesterol biosynthesis, HMG-Co reductase inhibitors lead to a decrease in inflammatory intermediaries. These pleiotropic effects include vasodilatation, anticoagulation, platelet inhibition, antioxidant, anti-inflammatory function, and decreased lymphocyte action. Statins stabilize atherosclerotic plaques through modulation of macrophage activation and through antithrombogenic, antiplatelet, and anti-inflammatory actions. Many of these beneficial effects occur within 24 h of statin initiation and before the significant reduction in serum cholesterol levels due to the improvement in endothelial function.1Skrlin S Hou V A review of perioperative statin therapy for noncardiac surgery.Semin Cardiothorac Vasc Anesth. 2010; 14: 283-290Crossref PubMed Scopus (16) Google Scholar These effects may partially oppose the impact of surgical stress on various organ systems during the perioperative period. Statins differ in their lipophilicity, half-life, and potency, which give them different potencies for extra-hepatic HMG-CoA reductase inhibition and pleiotropic effects.5Illingworth DR Tobert JA HMG-CoA reductase inhibitors.Adv Protein Chem. 2001; 56: 77-114Crossref PubMed Scopus (36) Google Scholar The aim of this paper is to investigate whether perioperative statin treatment improves clinical outcomes in statin-naive patients undergoing surgery. We defined patients as statin-naive if they were not already on long-time statin treatment for therapeutic options and if the treatment with statins was started before surgery with the aim of improving outcome. The clinical outcome was subdivided into the outcome measures of mortality, myocardial infarction, stroke, atrial fibrillation, and length of hospital stay. In this systematic review and meta-analysis, the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol was used.6Moher D Liberati A Tetzlaff J Altman DG Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.Br Med J. 2009; 339: b2535Crossref PubMed Scopus (15227) Google Scholar Study eligibility was determined independently by all authors. Studies were included if they met the following criteria: randomized controlled trials, patients aged 18 yr or older undergoing a surgical procedure, and patients who were not already on long-term statin treatment. Reported outcomes included at least one of the following: mortality, myocardial infarction, atrial fibrillation, stroke, and length of hospital stay. Randomized clinical trials were excluded if they were retrospective studies, if they did not involve a surgical procedure (percutaneous coronary intervention, cardioversion, follow-up without surgical intervention), if they did not report an outcome of interest, if patients were already on statin therapy before operation, or were not written in English. A literature search was performed in the electronic databases: Pubmed, Scopus, The Cochrane Library, OVID MEDLINE, EMBASE, and DARE in April 2013. References of other systematic reviews were also checked for relevant articles. The last search in Pubmed and Scopus was performed on April 28, 2013, and in The Cochrane Library, OVID MEDLINE, EMBASE, and DARE in April 2014. The search strategy consisted of multiple queries combining: HMG-CoA reductase inhibitors, statins, surgery, perioperative period, treatment outcome, mortality, myocardial infarction, atrial fibrillation, stroke, and length of hospital stay. In the electronic databases, restrictions were placed for English literature and in Pubmed, the search was limited to clinical trials. The titles and abstracts of the studies were reviewed. Subsequently, all publications were allocated by their study design: randomized clinical trial, cohort study, retrospective study, prospective study, review, or case–control study. Only the randomized controlled trials meeting the above-mentioned criteria were assessed for eligibility and used for data extraction. The detailed search strategy is available as supplementary material at British Journal of Anaesthesia online. The main outcome of the meta-analysis was the pooled risk ratio (RR) for the association between statin treatment and improved clinical postoperative outcome, calculated for the outcome measures—mortality, myocardial infarction, stroke, and atrial fibrillation. For data analysis, dichotomous variables and the Mantel–Haenszel statistical method were used. For the outcome variable length of hospital stay continuous variables and the Inverse Variance statistical method were used. For all analyses, the random effects analysis model was applied. Heterogeneity within the studies was estimated by the I2, which describes the percentage of total variation across studies that is due to heterogeneity rather than chance. A value of 0% indicates no observed heterogeneity, and larger values show increasing heterogeneity.7Higgins JPT Thompson SG Deeks JJ Altman DG Measuring inconsistency in meta-analyses.Br Med J. 2003; 327: 557-560Crossref PubMed Scopus (40126) Google Scholar Subgroup analyses were performed to determine if the type of surgery, statin agent used, and duration of statin intake before surgery influenced outcomes in patients. The type of surgery was divided into patients receiving non-cardiac surgery and cardiac surgery patients. Statins were classified according to their effectiveness in lowering LDL cholesterol levels. Atorvastatin and rosuvastatin were considered as high potency and fluvastatin, pravastatin, and simvastatin were considered as low-potency statins.8Conly J Clement F Tonelli M et al.Cost-effectiveness of the use of low- and high-potency statins in people at low cardiovascular risk.Can Med Assoc J. 2011; 183: E1180-E1188Crossref PubMed Scopus (23) Google Scholar A distinction was made regarding the duration of statin therapy before surgery, with patients divided into those on statin treatment for longer than 1 week and those on statins for 1 week or less before surgery. Sensitivity analyses were performed to estimate differences of treatment effects, excluding studies with unclear, low or high risk of bias, and different analysis methods. We tested for publication bias according to the Cochrane Statistical Methods Group. Bias was classified as unclear, low, or high risk for bias. Furthermore, we tested for publication bias using the Begg and Egger test and provided funnel plots. However, it should be noted that funnel plot asymmetry can have other causes besides publication bias.9Egger M Smith DG Schneider M Minder C Bias in meta-analysis detected by a simple, graphical test.Br Med J. 1997; 315: 629-634Crossref PubMed Scopus (34688) Google Scholar Finally, two bivariate meta-regression analyses were performed on all five outcome measures using study size and publication year as independent variables, respectively. All statistical analyses were performed in Review Manager (RevMan) Version 5.2 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012), except for the meta-regression analysis, which were performed in STATA 11.2 (StataCorp. LP, College Station, TX, USA). A P-value of 0.05 or less was considered to be statistically significant. The initial literature search yielded 576 manuscripts, of which 16 randomized controlled studies involving 2275 patients met the eligibility criteria (Fig. 1).10Christenson JT Preoperative lipid-control with simvastatin reduces the risk of postoperative thrombocytosis and thrombotic complications following CABG.Eur J Cardiothorac Surg. 1999; 15: 394-399Crossref PubMed Scopus (101) Google Scholar, 11Florens E Salvi S Peynet J et al.Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study.J Card Surg. 2001; 16: 232-239Crossref PubMed Scopus (33) Google Scholar, 12Durazzo AES Machado FS Ikeoka DT et al.Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial.J Vasc Surg. 2004; 39: 967-976Abstract Full Text Full Text PDF PubMed Scopus (495) Google Scholar, 13Chello M Patti G Candura D et al.Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery.Crit Care Med. 2006; 34: 660-667Crossref PubMed Scopus (197) Google Scholar, 14Patti G Chello M Candura D et al.Randomized trial of atorvastatin for reduction of post-operative 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: 1455-1461Crossref PubMed Scopus (542) Google Scholar, 15Caorsi C Pineda F Munoz C Pravastatin immunomodulates IL-6 and C-reactive protein, but not IL-1 and TNF-alpha, in cardio-pulmonary bypass.Eur Cytokine Netw. 2008; 19: 99-103PubMed Google Scholar, 16Mannacio VA Iorio D De Amicis V Di Lello F Musumeci F Effect of rosuvastatin pretreatment on myocardial damage after coronary surgery: a randomized trial.J Thorac Cardiovasc Surg. 2008; 136: 1541-1548Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar, 17Song YB On YK Kim JH et al.The effects of atorvastatin on the occurrence of postoperative atrial fibrillation after off-pump coronary artery bypass grafting surgery.Am Heart J. 2008; 156: 3739-37316Abstract Full Text Full Text PDF Scopus (103) Google Scholar, 18Berkan O Katrancioglu N Ozker E Ozerdem G Bakici Z Yilmaz MB Reduced P-selectin in hearts pretreated with fluvastatin: a novel benefit for patients undergoing open heart surgery.Thorac Cardiovasc Surg. 2009; 57: 91-95Crossref PubMed Scopus (32) Google Scholar, 19Dunkelgrun M Boersma E Schouten O et al.Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery, a randomized controlled trial (Decrease IV).Ann Surg. 2009; 249: 921-926Crossref PubMed Scopus (256) Google Scholar, 20Ji Q Mei Y Wang X et al.Effect of preoperative atorvastatin therapy on atrial fibrillation following off-pump coronary artery bypass grafting.Circ J. 2009; 73: 2244-2249Crossref PubMed Scopus (71) Google Scholar, 21Schouten O Boersma E Hoeks SE et al.Fluvastatin and perioperative events in patients undergoing vascular surgery.N Engl J Med. 2009; 361: 980-989Crossref PubMed Scopus (320) Google Scholar, 22Tamayo E Álvarez FJ Alonso O et al.Effects of simvastatin on systemic inflammatory responses after cardiopulmonary bypass.J Cardiovasc Surg. 2009; 50: 687-694PubMed Google Scholar, 23Spadaccio C Pollari F Casacalenda A et al.Atorvastain increases the number of endothelial progenitor cells after cardiac surgery: a randomized control study.J Cardiovasc Pharmacol. 2010; 55: 30-38Crossref PubMed Scopus (68) Google Scholar, 24Sun Y Ji Q Mei Y et al.Role of preoperative atorvastatin administration in protection against postoperative atrial fibrillation following conventional coronary artery bypass grafting.Int Heart J. 2011; 52: 7-11Crossref PubMed Scopus (62) Google Scholar, 25Baran Ç Durdu S Dalva K et al.Effects of preoperative short term use of atorvastatin on endothelial progenitor cells after coronary surgery: a randomized, controlled trial.Stem Cell Rev Rep. 2012; 8: 963-971Crossref PubMed Scopus (49) Google Scholar Included randomized controlled trials ranged in size from 20 to 533 patients, and evaluated different lipid-lowering therapies in patients undergoing non-cardiac, vascular, and cardiac surgery. Preoperative treatment ranged from 1 to 37 days and postoperative treatment ranged from 0 to 30 days (Table 1). All patients included in this review were statin-naive before randomization.Table 1Characteristics of included randomized clinical trials. R, randomized; DB, double blind; PC, patient-controlled trial; CABG, coronary artery bypass graft; NCV, non-cardiovascularFirst authorYearStudy designn [males (%)]Age (yr)Type of surgeryTherapy (mg day−1)Treatment (days)PreoperativePostoperativeChristenson10Christenson JT Preoperative lipid-control with simvastatin reduces the risk of postoperative thrombocytosis and thrombotic complications following CABG.Eur J Cardiothorac Surg. 1999; 15: 394-399Crossref PubMed Scopus (101) Google Scholar1999R, PC77 (80.5)63.4CABGSimvastatin 2028Florens11Florens E Salvi S Peynet J et al.Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study.J Card Surg. 2001; 16: 232-239Crossref PubMed Scopus (33) Google Scholar2001R, PC20 (70.0)65.0CABGAtorvastatin 4011Durazzo12Durazzo AES Machado FS Ikeoka DT et al.Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial.J Vasc Surg. 2004; 39: 967-976Abstract Full Text Full Text PDF PubMed Scopus (495) Google Scholar2004R, DB, PC100 (79.0)67.2VascularAtorvastatin 203015Chello13Chello M Patti G Candura D et al.Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery.Crit Care Med. 2006; 34: 660-667Crossref PubMed Scopus (197) Google Scholar2006R, DB, PC41 (75.6)64.7CABGAtorvastatin 2021Patti14Patti G Chello M Candura D et al.Randomized trial of atorvastatin for reduction of post-operative 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: 1455-1461Crossref PubMed Scopus (542) Google Scholar2006R, DB, PC200 (73.5)66.4CABGAtorvastatin 40730Caorsi15Caorsi C Pineda F Munoz C Pravastatin immunomodulates IL-6 and C-reactive protein, but not IL-1 and TNF-alpha, in cardio-pulmonary bypass.Eur Cytokine Netw. 2008; 19: 99-103PubMed Google Scholar2008R, PC43 (83.7)68.1CABGPravastatin 4027Mannacio16Mannacio VA Iorio D De Amicis V Di Lello F Musumeci F Effect of rosuvastatin pretreatment on myocardial damage after coronary surgery: a randomized trial.J Thorac Cardiovasc Surg. 2008; 136: 1541-1548Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar2008R, DB, PC200 (72.5)60.3CABGRosuvastatin 2070Song17Song YB On YK Kim JH et al.The effects of atorvastatin on the occurrence of postoperative atrial fibrillation after off-pump coronary artery bypass grafting surgery.Am Heart J. 2008; 156: 3739-37316Abstract Full Text Full Text PDF Scopus (103) Google Scholar2008R, PC124 (65.3)62.9CABGAtorvastatin 20330Berkan18Berkan O Katrancioglu N Ozker E Ozerdem G Bakici Z Yilmaz MB Reduced P-selectin in hearts pretreated with fluvastatin: a novel benefit for patients undergoing open heart surgery.Thorac Cardiovasc Surg. 2009; 57: 91-95Crossref PubMed Scopus (32) Google Scholar2009R, DB, PC46 (63.0)66.5CABGFluvastatin 8021Dunkelgrun19Dunkelgrun M Boersma E Schouten O et al.Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery, a randomized controlled trial (Decrease IV).Ann Surg. 2009; 249: 921-926Crossref PubMed Scopus (256) Google Scholar2009R, PC533 (59.3)65.5NCVFluvastatin 803430Ji20Ji Q Mei Y Wang X et al.Effect of preoperative atorvastatin therapy on atrial fibrillation following off-pump coronary artery bypass grafting.Circ J. 2009; 73: 2244-2249Crossref PubMed Scopus (71) Google Scholar2009R, DB, PC140 (69.3)65.5CABGAtorvastatin 207Schouten21Schouten O Boersma E Hoeks SE et al.Fluvastatin and perioperative events in patients undergoing vascular surgery.N Engl J Med. 2009; 361: 980-989Crossref PubMed Scopus (320) Google Scholar2009R, DB, PC497 (74.8)65.9VascularFluvastatin 803730Tamayo22Tamayo E Álvarez FJ Alonso O et al.Effects of simvastatin on systemic inflammatory responses after cardiopulmonary bypass.J Cardiovasc Surg. 2009; 50: 687-694PubMed Google Scholar2009R, PC44 (79.5)67.9CABGSimvastatin 2021Spadaccio23Spadaccio C Pollari F Casacalenda A et al.Atorvastain increases the number of endothelial progenitor cells after cardiac surgery: a randomized control study.J Cardiovasc Pharmacol. 2010; 55: 30-38Crossref PubMed Scopus (68) Google Scholar2010R, PC50 (54.0)65.4CABGAtorvastatin 2021Sun24Sun Y Ji Q Mei Y et al.Role of preoperative atorvastatin administration in protection against postoperative atrial fibrillation following conventional coronary artery bypass grafting.Int Heart J. 2011; 52: 7-11Crossref PubMed Scopus (62) Google Scholar2011R, PC100 (67.0)64.5CABGAtorvastatin 207Baran25Baran Ç Durdu S Dalva K et al.Effects of preoperative short term use of atorvastatin on endothelial progenitor cells after coronary surgery: a randomized, controlled trial.Stem Cell Rev Rep. 2012; 8: 963-971Crossref PubMed Scopus (49) Google Scholar2012R, DB, PC60 (61.7)61.5CABGAtorvastatin 4014 Open table in a new tab According to the Cochrane Statistical Methods Group, the risk of bias was categorized as unclear in eight studies,10Christenson JT Preoperative lipid-control with simvastatin reduces the risk of postoperative thrombocytosis and thrombotic complications following CABG.Eur J Cardiothorac Surg. 1999; 15: 394-399Crossref PubMed Scopus (101) Google Scholar, 11Florens E Salvi S Peynet J et al.Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study.J Card Surg. 2001; 16: 232-239Crossref PubMed Scopus (33) Google Scholar, 13Chello M Patti G Candura D et al.Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery.Crit Care Med. 2006; 34: 660-667Crossref PubMed Scopus (197) Google Scholar, 15Caorsi C Pineda F Munoz C Pravastatin immunomodulates IL-6 and C-reactive protein, but not IL-1 and TNF-alpha, in cardio-pulmonary bypass.Eur Cytokine Netw. 2008; 19: 99-103PubMed Google Scholar, 18Berkan O Katrancioglu N Ozker E Ozerdem G Bakici Z Yilmaz MB Reduced P-selectin in hearts pretreated with fluvastatin: a novel benefit for patients undergoing open heart surgery.Thorac Cardiovasc Surg. 2009; 57: 91-95Crossref PubMed Scopus (32) Google Scholar, 22Tamayo E Álvarez FJ Alonso O et al.Effects of simvastatin on systemic inflammatory responses after cardiopulmonary bypass.J Cardiovasc Surg. 2009; 50: 687-694PubMed Google Scholar, 23Spadaccio C Pollari F Casacalenda A et al.Atorvastain increases the number of endothelial progenitor cells after cardiac surgery: a randomized control study.J Cardiovasc Pharmacol. 2010; 55: 30-38Crossref PubMed Scopus (68) Google Scholar, 24Sun Y Ji Q Mei Y et al.Role of preoperative atorvastatin administration in protection against postoperative atrial fibrillation following conventional coronary artery bypass grafting.Int Heart J. 2011; 52: 7-11Crossref PubMed Scopus (62) Google Scholar high in two studies,17Song YB On YK Kim JH et al.The effects of atorvastatin on the occurrence of postoperative atrial fibrillation after off-pump coronary artery bypass grafting surgery.Am Heart J. 2008; 156: 3739-37316Abstract Full Text Full Text PDF Scopus (103) Google Scholar, 19Dunkelgrun M Boersma E Schouten O et al.Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery, a randomized controlled trial (Decrease IV).Ann Surg. 2009; 249: 921-926Crossref PubMed Scopus (256) Google Scholar and low in six studies (Table 2).12Durazzo AES Machado FS Ikeoka DT et al.Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial.J Vasc Surg. 2004; 39: 967-976Abstract Full Text Full Text PDF PubMed Scopus (495) Google Scholar, 14Patti G Chello M Candura D et al.Randomized trial of atorvastatin for reduction of post-operative 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: 1455-1461Crossref PubMed Scopus (542) Google Scholar, 16Mannacio VA Iorio D De Amicis V Di Lello F Musumeci F Effect of rosuvastatin pretreatment on myocardial damage after coronary surgery: a randomized trial.J Thorac Cardiovasc Surg. 2008; 136: 1541-1548Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar, 20Ji Q Mei Y Wang X et al.Effect of preoperative atorvastatin therapy on atrial fibrillation following off-pump coronary artery bypass grafting.Circ J. 2009; 73: 2244-2249Crossref PubMed Scopus (71) Google Scholar, 21Schouten O Boersma E Hoeks SE et al.Fluvastatin and perioperative events in patients undergoing vascular surgery.N Engl J Med. 2009; 361: 980-989Crossref PubMed Scopus (320) Google Scholar, 25Baran Ç Durdu S Dalva K et al.Effects of preoperative short term use of atorvastatin on endothelial progenitor cells after coronary surgery: a randomized, controlled trial.Stem Cell Rev Rep. 2012; 8: 963-971Crossref PubMed Scopus (49) Google ScholarTable 2Risk of bias in the included studies. +, Low risk of bias; −, high risk of bias; ?, unclear risk of biasChristenson10Christenson JT Preoperative lipid-control with simvastatin reduces the risk of postoperative thrombocytosis and thrombotic complications following CABG.Eur J Cardiothorac Surg. 1999; 15: 394-399Crossref PubMed Scopus (101) Google ScholarFlorens11Florens E Salvi S Peynet J et al.Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study.J Card Surg. 2001; 16: 232-239Crossref PubMed Scopus (33) Google ScholarDurazzo12Durazzo AES Machado FS Ikeoka DT et al.Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial.J Vasc Surg. 2004; 39: 967-976Abstract Full Text Full Text PDF PubMed Scopus (495) Google ScholarChello13Chello M Patti G Candura D et al.Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery.Crit Care Med. 2006; 34: 660-667Crossref PubMed Scopus (197) Google ScholarPatti14Patti G Chello M Candura D et al.Randomized trial of atorvastatin for reduction of post-operative 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: 1455-1461Crossref PubMed Scopus (542) Google ScholarCaorsi15Caorsi C Pineda F Munoz C Pravastatin immunomodulates IL-6 and C-reactive protein, but not IL-1 and TNF-alpha, in cardio-pulmonary bypass.Eur Cytokine Netw. 2008; 19: 99-103PubMed Google ScholarMannacio16Mannacio VA Iorio D De Amicis V Di Lello F Musumeci F Effect of rosuvastatin pretreatment on myocardial damage after coronary surgery: a randomized trial.J Thorac Cardiovasc Surg. 2008; 136: 1541-1548Abstract Full Text Full Text PDF PubMed Scopus (119) Google ScholarSong17Song YB On YK Kim JH et al.The effects of atorvastatin on the occurrence of postoperative atrial fibrillation after off-pump coronary artery bypass grafting surgery.Am Heart J. 2008; 156: 3739-37316Abstract Full Text Full Text PDF Scopus (103) Google ScholarBerkan18Berkan O Katrancioglu N Ozker E Ozerdem G Bakici Z Yilmaz MB Reduced P-selectin in hearts pretreated with fluvastatin: a novel benefit for patients undergoing open heart surgery.Thorac Cardiovasc Surg. 2009; 57: 91-95Crossref PubMed Scopus (32) Google ScholarDunkelgrun19Dunkelgrun M Boersma E Schouten O et al.Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery, a randomized controlled trial (Decrease IV).Ann Surg. 2009; 249: 921-926Crossref PubMed Scopus (256) Google ScholarJi20Ji Q Mei Y Wang X et al.Effect of preoperative atorvastatin therapy on atrial fibrillation following off-pump coronary artery bypass grafting.Circ J. 2009; 73: 2244-2249Crossref PubMed Scopus (71) Google ScholarSchouten21Schouten O Boersma E Hoeks SE et al.Fluvastatin and perioperative events in patients undergoing vascula
Referência(s)