Preoperative statin therapy for patients undergoing cardiac surgery

Kuhn, Elmar; Slottosch, Ingo; Wahlers, Thorsten; Liakopoulos, Oliver J.

doi:10.1002/14651858.cd008493.pub3

Cited by 39 publications

(43 citation statements)

References 125 publications

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“…Several studies provide evidence for beneficial effects of statins on atrial fibrillation (AF) and outcomes after cardiac surgery 44-47 In contrast, in a study with 1922 patients in sinus rhythm who underwent elective cardiac surgery and received perioperative rosuvastatin 20 mg or placebo, statin therapy did not prevent postoperative AF or myocardial damage. 48 Similarly, in a large trial among patients undergoing cardiac surgery, atorvastatin treatment did not reduce the risk of acute kidney injury.…”

Section: Introductionmentioning

confidence: 99%

Pleiotropic Effects of Statins on the Cardiovascular System

Oesterle

Laufs

Liao

2017

Circulation Research

952

684

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The 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors (statins), have been used for thirty years to prevent coronary artery disease and stroke. Their primary mechanism of action is the lowering of serum cholesterol through inhibiting hepatic cholesterol biosynthesis thereby upregulating the hepatic low-density lipoprotein (LDL) receptors and increasing the clearance of LDL-cholesterol (LDL-C). Statins may exert cardiovascular protective effects that are independent of LDL-C lowering called “pleiotropic” effects. Because statins inhibit the production of isoprenoid intermediates in the cholesterol biosynthetic pathway, the post-translational prenylation of small guanosine triphosphate binding proteins such as Rho and Rac, and their downstream effectors such as Rho kinase and nicotinamide adenine dinucleotide phosphate oxidases are also inhibited. In cell culture and animal studies, these effects alter the expression of endothelial nitric oxide synthase, the stability of atherosclerotic plaques, the production of pro-inflammatory cytokines and reactive oxygen species, the reactivity of platelets, and the development of cardiac hypertrophy and fibrosis. The relative contributions of statin pleiotropy to clinical outcomes, however, remain a matter of debate and are hard to quantify since the degree of isoprenoid inhibition by statins correlates to some extent with the amount of LDL-C reduction. This review examines some of the currently proposed molecular mechanisms for statin pleiotropy and discusses whether they could have any clinical relevance in cardiovascular disease.

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Section: Introductionmentioning

confidence: 99%

Pleiotropic Effects of Statins on the Cardiovascular System

Oesterle

Laufs

Liao

2017

Circulation Research

952

684

View full text Add to dashboard Cite

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“…However, RCTs support the lack of a kidney-protective effect [21, 22, 42, 60, 61], as do the most recent systematic reviews [17, 60]. The largest RCT performed so far showed that rosuvastatin therapy resulted in a significantly higher rate of AKI and higher plasma creatinine levels compared to placebo at 48 hours after cardiac surgery [22].…”

Section: Discussionmentioning

confidence: 99%

Perioperative statin therapy in cardiac surgery: a meta-analysis of randomized controlled trials

et al. 2016

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BackgroundSeveral 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.MethodsElectronic 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.ResultsWe 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.ConclusionsThere 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1560-6) contains supplementary material, which is available to authorized users.

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“…This analysis includes data from 409 trials, extracted from 37 Cochrane reviews , representing 51 countries with 89,389 participants. Trial selection is shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

The developing world of pre‐operative optimisation: a systematic review of Cochrane reviews

2018

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Pre-operative optimisation is a heterogenous group of interventions aimed at improving peri-operative outcomes. To understand the evidence for pre-operative optimisation in the developing world, we systematically reviewed Cochrane reviews on the topic according to the Human Developmental Index (HDI) of the country where patient recruitment occurred. We used summary statistics and cartograms to describe the HDI, year of publication, timing of pre-operative intervention and risk of bias associated with each included trial. We assessed the impact of multinational trials on the risk of bias introduced by countries of differing HDI. Fourhundred and nine trials representing 51 countries and 89,389 randomly allocated participants were summarised in this review. Four-hundred and nineteen out of 451 (93%) trial populations (i.e. a group of study participants from one country) were from high and very high HDI countries. The median (IQR [range]) HDI of countries were 0.862 (0.806-0.892 [0.445-0.949]). Three of the 409 included trials were multinational, representing 32 countries and 37,736 out of 89,389 (42.2%) included participants. Africa was the least represented continent, with only 4 included trials and 566 participants, of which 62.3% were from one multinational trial. The overall risk of bias was high or unclear in 381 out of 409 (93%) trials. Inclusion of multinational trials decreased the proportion of trial populations introducing high or unclear risk of bias by 9.4% (95%CI 5.1-13.7; p < 0.0001). Half of the world's population live in low-and middle-HDI countries. This population is poorly represented in systematically reviewed evidence on pre-operative optimisation. Multinational trials increase the knowledge contribution from low-and middle-HDI countries and decrease risk of bias in systematic reviews. Anaesthesia 2019, 74, 89-99 du Toit et al. | Developing world of pre-operative optimisation

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Preoperative statin therapy for patients undergoing cardiac surgery

Cited by 39 publications

References 125 publications

Pleiotropic Effects of Statins on the Cardiovascular System

Pleiotropic Effects of Statins on the Cardiovascular System

Perioperative statin therapy in cardiac surgery: a meta-analysis of randomized controlled trials

The developing world of pre‐operative optimisation: a systematic review of Cochrane reviews

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