Progress in Perioperative Medicine: Focus on Statins

Annals of Cardiac Anaesthesia, 2017

Statins belong to a specific group of drugs that have been described for their ability to control hyperlipidemia as well as for other pleiotropic effects such as improving vascular endothelial function, inhibition of oxidative stress pathways, and anti-inflammatory actions. Accumulating clinical evidence strongly suggests that statins also have a beneficial effect on perioperative morbidity and mortality. Therefore, this review aims to present all recent and pooled data on statin treatment in the perioperative setting as well as to highlight considerations regarding their indications and therapeutic application.

Journal of the American College of Cardiology, 2005

We sought to assess whether statins may decrease cardiac complications in patients undergoing noncardiac vascular surgery. BACKGROUND Cardiovascular complications account for considerable morbidity in patients undergoing noncardiac surgery. Statins decrease cardiac morbidity and mortality in patients with coronary disease, and the beneficial treatment effect is seen early, before any measurable increase in coronary artery diameter.

International Journal of Surgery, 2009

Background: Aside from their cholesterol-lowering effects statins are known to have a range of other 'pleiotropic' effects. We present an overview of the basic science behind these effects and then review clinical trials and the current role of statins relevant to modern surgical practice.

Systematic reviews, 2017

Preliminary evidence suggests statins may reduce major perioperative vascular events. However, evidence is limited to observational studies, underpowered trials, and non-comprehensive systematic reviews. This review aims to assess the effects of perioperative statin use on cardiovascular complications in patients submitted to non-cardiac surgery. We will search MEDLINE/PubMed, EMBASE, LILACS, CENTRAL, Web of Science, and CINAHL for randomized controlled trials assessing the effects of perioperative statin use in adults undergoing non-cardiac surgery and reporting cardiovascular complications. For patients already using statins for hyperlipidemia, a preoperative loading dose of statin is required in the experimental group. We will place no language or publication restriction on our search. Teams of two reviewers will independently assess eligibility and risk of bias, and will extract data from the included trials. Our primary outcome is a combination of cardiovascular mortality or no...

Journal of Cardiothoracic and Vascular Anesthesia, 2015

Critical Care, 2016

BACKGROUND: Several studies suggest beneficial effects of perioperative statin therapy on postoperative outcome after cardiac surgery. However, recent randomized controlled trials (RCTs) show potential detrimental effects. The objective of this systematic review is to examine the association between perioperative statin therapy and clinical outcomes in cardiac surgery patients. METHODS: Electronic databases were searched up to 1 November 2016 for RCTs of preoperative statin therapy versus placebo or no treatment in adult cardiac surgery. Postoperative outcomes were acute kidney injury, atrial fibrillation, myocardial infarction, stroke, infections, and mortality. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using fixed-effects meta-analyses. Primary analysis was restricted to trials with low risk of bias according to Cochrane methodology, and sensitivity analyses examined whether the risk of bias of included studies was associated with different results. We performed trial sequential analysis (TSA) to test the strength of the results. RESULTS: We included data from 23 RCTs involving 5102 patients. Meta-analysis of trials with low risk of bias showed that statin therapy was associated with an increase in acute kidney injury (314 of 1318 (23.82%) with statins versus 262 of 1319 (19.86%) with placebo; OR 1.26 (95%CI 1.05 to 1.52); p = 0.01); these results were supported by TSA. No difference in postoperative atrial fibrillation, myocardial infarction, stroke, infections, or mortality was present. On sensitivity analysis, statin therapy was associated with a slight increase in hospital mortality. Meta-analysis including also trials with high or unclear risk of bias showed no beneficial effects of statin therapy on any postoperative outcomes. CONCLUSIONS: There is no evidence that statin therapy in the days prior to cardiac surgery is beneficial for patients' outcomes. Particularly, statins are not protective against postoperative atrial fibrillation, myocardial infarction, stroke, or infections. Statins are associated with a possible increased risk of acute kidney injury and a detrimental effect on hospital survival could not be excluded. Future RCTs should further evaluate the safety profile of this therapy in relation to patients' outcomes and assess the more appropriate time point for discontinuation of statins before cardiac surgery. (2016). Perioperative statin therapy in cardiac surgery: a metaanalysis of randomized controlled trials. Critical Care, 20(1):395.

BMJ, 2006

Objective To determine the strength of evidence underlying recommendations for use of statins during the perioperative period to reduce the risk of cardiovascular events. Design Systematic review of studies with concurrent control groups. Data sources Four electronic databases, the references of identified studies, international experts on perioperative medicine, and the authors of the primary studies. Review methods Two reviewers independently extracted data from studies that reported acute coronary syndromes or mortality in patients receiving or not receiving statins during the perioperative period. Main outcome measure Random effects summary odds ratios for death or acute coronary syndrome during the perioperative period. Results 18 studies-two randomised trials (n = 177), 15 cohort studies (n = 799 632), and one case-control study (n = 480)-assessed whether statins provide perioperative cardiovascular protection; 12 studies enrolled patients undergoing non-cardiac vascular surgery, four enrolled patients undergoing coronary bypass surgery, and two enrolled patients undergoing various surgical procedures. In the randomised trials the summary odds ratio for death or acute coronary syndrome during the perioperative period with statin use was 0.26 (95% confidence interval 0.07 to 0.99) and the summary odds ratio in the cohort studies was 0.70 (0.57 to 0.87). Although the pooled cohort data provided a statistically significant result, statins were not randomly allocated, results in retrospective studies were larger (odds ratio 0.65, 0.50 to 0.84) than those in the prospective cohorts (0.91, 0.65 to 1.27), and dose, duration, and safety of statin use was not reported. Conclusion The evidence base for routine administration of statins to reduce perioperative cardiovascular risk is inadequate. References w1-w18 are on bmj.com

Anesthesiology, 2011

Background: Chronic statin therapy is associated with reduced postoperative mortality. Renal and cardiovascular benefits have been described, but the effect of chronic statin therapy on postoperative adverse events has not yet been explored. Methods: In this observational study involving 1,674 patients undergoing aortic reconstruction, we prospectively assessed chronic statin therapy compared with no statin therapy, with regard to serious outcomes, by propensity score and multivariable methods. Results: In propensity-adjusted multivariable logistic regression (c-index: 0.83), statins were associated with an almost threefold reduction in the risk of death in patients undergoing major vascular surgery (odds ratio: 0.40; 95% CI: 0.28 -0.59) and an almost twofold reduction in the risk of postoperative myocardial infarction (odds ratio: 0.52; 95% CI: 0.38 -0.71). Likewise, the use of chronic statin therapy was associated with a

Clinical Cardiology, 2013

Background: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) reduce perioperative cardiac events in high-risk patients undergoing cardiovascular surgery. However, there is paucity of data on the role of statins in patients undergoing intermediate-risk noncardiac, nonvascular surgery (NCNVS). Hypothesis: Statins are cardioprotective in intermediate-risk NCNVS. Methods: We identified a retrospective cohort of patients undergoing intermediate risk NCNVS. Our composite end point included 30-day all-cause mortality, atrial fibrillation (AF), and nonfatal myocardial infarction (MI). A stepwise logistic regression with adjustment using propensity scores was performed to determine if statin therapy was independently associated with the risk reduction of adverse postoperative cardiovascular outcomes. Results: We identified 752 patients. Seventy-five of them (9.97%) developed composite end points; 10 (1.33%) had in-hospital nonfatal MI, 44 (5.85%) developed AF, and 35 (4.65%) died within 30 days. The 30-day all-cause mortality was 31/478 (6.48%) among statin nonusers vs 4/274 (1.45%) for statin users (P < 0.002). As compared with nonusers, patients on statin therapy had a 5-fold reduced risk of 30-day all-cause mortality. Statin therapy was associated with decreased CEP after adjusting for baseline characteristics, with a propensity score to predict use of statins (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.30-0.97, P = 0.039). After further adjustment for propensity score, diabetes mellitus, percutaneous coronary intervention, and prior coronary artery bypass grafting, statin therapy proved beneficial (OR: 0.51, 95% CI: 0.28-0.92, P = 0.026). Conclusions: Statin use in the perioperative period was associated with a reduction in cardiovascular adverse events and 30-day all-cause mortality in patients undergoing intermediate-risk NCNVS.

2009

Background. It has been suggested that the routine use of statins preoperatively would reduce the risk of postoperative infection. We conducted this study to explore whether preoperative statin use was associated with infection after cardiac surgery (recipients of which have a higher-than-average risk of postoperative infection). Methods. We performed secondary analysis of data collected in a prospective cohort study of adults who underwent nontransplant cardiac surgery in a university hospital during the period January 1999 through December 2005. Outcomes were ascertained in a blinded and independent fashion. Results. Of the 7733 patients, 2657 (34%) were taking statins preoperatively; the proportion increased from 16% during 1999-2000 to 53% during 2003-2005 (, by test for trend). There was no association between P ! .001 preoperative statin use and postoperative infection: 214 statin users (8.1%) versus 425 statin nonusers (8.4%) developed an infection within 30 days after surgery. Factors associated with increased risk of infection after cardiac surgery included diabetes mellitus, heart failure, chronic obstructive pulmonary disease, increasing age, elevated baseline creatinine level, and longer duration of cardiopulmonary bypass but not statin use (adjusted odds ratio, 1.08; 95% confidence interval, 0.89-1.31). Conclusions. Preoperative statin use was not associated with a reduction in the rate of postoperative infection among patients who underwent cardiac surgery. This lack of apparent benefit for high-risk patients argues against the routine use of statins as a preoperative strategy for lower-risk patients and supports calls for randomized trials to define whether preoperative statin use influences postoperative rates of infection.

International journal of cardiology, 2005

Background: Cardiac surgery carries a 2-3% early mortality due in part to perioperative myocardial infarction (PMI), low-output syndrome (LOS), and arrhythmias. Statins attenuate thrombogenesis, normalize endothelial dysfunction, and mitigate the oxidative stress and reperfusion injury characteristic of such complications. We sought to determine whether preoperative statin use is associated with reduced early mortality and major morbidity following cardiac surgery. Methods: Patients having isolated coronary artery bypass grafting (CABG), valve, or combined CABG/valve surgery between May 1998 and June 2003 (n=5469) were identified. A logistic regression model was generated to determine the association of preoperative statin use with in-hospital mortality (IHM). Propensity score analysis was used to match two subgroups of patients (Group I, on statins, n=1443; Group II, not on statins, n=1443) on multiple factors known to impact cardiac surgical outcome. Outcomes assessed were IHM, intra-aortic balloon pump (IABP) use, PMI, prolonged (N24 h) ventilation (p-vent), stroke, and a composite end point (comp) defined as any one or more of the above. Results: Of the 5469 patients, 3555 were on statins and 1914 were not. Unadjusted rates of IHM (2.6% vs. 5.0%), stroke (1.9% vs. 3.3%), pvent (10.2% vs. 16.6%), and comp (12.7% vs. 19.5%) were lower ( p=0.0001) in patients receiving statins. After adjustment, statin use was not associated with a reduction in IHM (OR=0.9, 95% CI=0.6-1.2, p=0.36) or comp (OR=0.9, 95% CI=0.8-1.1, p=0.31). After matching two subgroups using propensity score for statin, no significant differences were found in any of the adjusted outcomes for Group I vs. Group II: IHM (4.0% vs. 4.6%), PMI (1.5% vs. 1.1%), p-vent (15.8% vs. 15.7%), IABP use (2.0% vs. 2.3%), stroke (3.0% vs. 3.3%), and comp (19.1% vs. 18.8%). Conclusions: Preoperative statin use is not associated with a reduction in IHM or major morbidity following cardiac surgery.

Scientific Reports, 2017

A controversy effect of perioperative statin use for preventing postoperative atrial fibrillation (POAF) and acute kidney injury (AKI) after cardiac surgery still remains. We thus performed current systematic review and meta-analysis to comprehensively evaluate effects of statin in cardiac surgery. 22 RCTs involving 5243 patients were included. Meta-analysis of 18 randomized controlled trials with 3995 participants suggested that perioperative statin use could decrease the risk of POAF (relative risk [RR] 0.69, 95%CI 0.56 to 0.86, P = 0.001), with a moderate heterogeneity (I 2 = 65.7%, P H < 0.001). And the beneficial effect was found only in patients receiving coronary artery bypass graft (CABG), but not in patients undergoing valve surgery. However, perioperative statin use was not associated with lower risks of AKI (RR 0.98, 95%CI 0.70 to 1.35, P = 0.884, I 2 = 33.9%, P H = 0.157) or myocardial infarction (MI) (RR 0.84, 95%CI 0.58 to 1.23, P = 0.380, I 2 = 0%, P H = 0.765), and even an increased trend of AKI was observed in patients with valve surgery. Perioperative statin use could decrease the inflammation response with no impact on clinical outcomes. In conclusion, perioperative statin use is useful in preventing POAF, particularly in patients with CABG, and ameliorate inflammation, while it has no effect on AKI and MI after cardiac surgery. Despite advanced protection of cardiopulmonary bypass (CPB) and other techniques supported during cardiac surgery, the major post-operation complications are still like Pandora's Box, contributing to the substantial mortality and morbidity and increasing medical costs 1, 2. Currently, researches demonstrated that these complications were mainly driven by post-perfusion syndrome, oxidative stress and release of inflammation cytokines after cardiac surgery 3, 4. Though as transient complications, the indisputable fact is that postoperative atrial fibrillation (POAF) and acute kidney injury (AKI), the most frequent complications after cardiac surgery, are independent risk factors related to poor prognosis in patients received cardiac surgery 5, 6. Observational studies, randomized controlled trials (RCTs), and meta-analysis have demonstrated that perioperative statin use could decrease the incidence of POAF and AKI 7-10 , and latest guidelines suggested statins should be administrated in all patients undergoing coronary artery bypass graft (CABG) except for specific contradictions 11. However, recent studies fail to verify the beneficial effect of statin use in cardiac surgery, and the controversy still exists 12-16. Though many meta-analyses have been performed, this issue is still fuzziness. Therefore, we further systematically summarized current evidence of RCTs and meta-analyses to provide a

British Journal of Anaesthesia, 2009

The use of statins is widespread and many patients presenting for surgery are regularly taking them. There is evidence that statins have beneficial effects beyond those of lipid lowering, including reducing the perioperative risk of cardiac complications and sepsis. This review addresses the cellular mechanisms by which statins may produce these effects. Statins appear to have actions on vascular nitric oxide through the balance of inducible and endothelial nitric oxide synthase. The clinical evidence for these benefits is also briefly reviewed with the objective of clarifying the current status of statin use in the perioperative period. There is reasonably strong evidence that patients already taking statins should continue on them perioperatively. However, the evidence for the prophylactic use of statins perioperatively is weak and lacks prospective controlled studies.

The Journal of thoracic and cardiovascular surgery, 2015

Statins are being used with increasing frequency for indications beyond lipid-lowering therapy. In the perioperative setting, the use of statins as anti-inflammatory agents has been an area of growing interest. Despite the early clinical adoption, the data are controversial. Herein we review the available clinical trials examining the effects of statin therapy on perioperative markers of inflammation in cardiac and thoracic surgery.

2010

Background. Delirium after cardiac operations is associated with significant morbidity and death. Statins have been recently suggested to exert protective cerebral effects. This study investigated whether preoperative statins were associated with decreased incidence of postoperative delirium in patients undergoing coronary artery bypass grafting.