Abstract
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.
Highlights
Several studies suggest beneficial effects of perioperative statin therapy on postoperative outcome after cardiac surgery
Statin treatment was considered an attractive therapy for reducing acute kidney injury (AKI) following cardiac surgery [54], an idea mainly based on retrospective data [16, 55,56,57,58,59], and according to this hypothesis, some large randomized controlled trials (RCTs) have been performed to test whether statins effectively decrease postoperative AKI [21, 42]
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]
Summary
Several studies suggest beneficial effects of perioperative statin therapy on postoperative outcome after cardiac surgery. Recent randomized controlled trials (RCTs) show potential detrimental effects. Postoperative complications after cardiac surgery are associated with higher morbidity and mortality, and increased costs [1]. Knowledge of pleiotropic anti-inflammatory effects of statins [11, 12] has led to consider statins a potential therapy able to modulate the inflammatory response to cardiac surgery. In support of this assumption, several randomized controlled trials (RCTs), reporting on inflammatory markers and statin use in perioperative cardiac surgery, have demonstrated reduction in inflammatory cytokines [12]. The largest recently published RCTs show that perioperative statins do not prevent postoperative AF or myocardial damage and could be even associated with higher postoperative AKI [21, 22]
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