Preoperative statin therapy for patients undergoing cardiac surgery

Cardiac surgery offers a highly efficient therapeutic option to patients with heart disease, but bears at the same time a significant risk of the development of post-operative adverse events. Despite the increasing proportion of patients referring to cardiac surgery with major comorbidities, the operative results have remained stable during the past decades due to significant advancements of surgical techniques. Nonetheless, perioperative care of patients referring to cardiac surgery still needs to be optimized to further improve patients´ outcomes. Statins (HMG-CoA reductase inhibitors) are known to provide beneficial effects beyond their lipid-lowering properties in patients with atherosclerotic cardiovascular disease in terms of a reduction of mortality from adverse cardiovascular events. However, evidence for the beneficial statin effects for patients undergoing cardiac surgery is inconsistent since it is mainly extracted from observational studies and only a few small randomized clinical trials.

The aim of this review is to determine the current evidence of preoperative statin therapy on the reduction of major adverse cardiovascular events in patients referred to cardiac surgical procedures.

We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the metaRegister of Controlled Trials. Eleven studies dating from 1999 to 2010 with a total of 984 participants undergoing cardiac surgical procedures were identified. All included trials were randomized studies comparing statin treatment with a control intervention (no statin medication) or placebo in patients that were predominantly referred to coronary artery bypass grafting surgery.

Preoperative statin therapy resulted in a reduction of post-operative AF and a shorter length of stay both on the ICU and in the hospital. Although statin-pretreatment was associated with lower incidences of myocardial infarction and renal failure, these results did not reach statistical significance. Furthermore, statin therapy had no impact on short-term mortality and post-operative stroke. No serious side effects of a statin therapy prior to cardiac surgery were reported. However, all analysed studies included mainly patients undergoing coronary bypass operations, thus, the results of this study may not be generalisable to patients undergoing cardiac procedures other than coronary artery bypass grafting.

Authors' conclusions: 

Preoperative statin therapy reduces the odds of post-operative atrial fibrillation (AF) and shortens the stay on the ICU and in the hospital. Statin pretreatment had no influence on perioperative mortality, stroke, myocardial infarction or renal failure. Since analysed studies included mainly patients undergoing myocardial revascularizations the results cannot be extrapolated to patients undergoing other cardiac procedures such as heart valve or aortic surgery.

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Background: 

Patients referred to cardiac surgery for cardiovascular disease are at significant risk for the development of post-operative major adverse events despite significant advances in surgical techniques and perioperative care. Statins (HMG-CoA reductase inhibitors) have gained a pivotal role in the primary and secondary prevention of coronary artery disease, and are thought to improve perioperative outcomes in patients undergoing cardiac surgery.

Objectives: 

To determine the effectiveness of a preoperative statin therapy in patients undergoing cardiac surgery.

Search strategy: 

We searched CENTRAL (Issue 2 of 4, 2010 on The Cochrane Library), MEDLINE (1950 to May, Week 1 2010), EMBASE (1980 to 2010 Week 19), and the metaRegister of Controlled Trials. Additionally, ongoing trials were searched through the National Research Register, the ClinicalTrials.gov registry and grey literature. Conference indices from relevant scientific meetings (2006-2009) were screened online for eligible trials. No language restrictions were applied.

Selection criteria: 

All randomized controlled trials comparing any statin treatment before cardiac surgery, for any given duration and dose, to no preoperative statin therapy (standard of care) or placebo.

Data collection and analysis: 

Two authors evaluated trial quality and extracted data from titles and abstracts identified from the electronic database searches according to pre-defined criteria. Accordingly, full text articles of potentially relevant studies that met the inclusion criteria were retrieved to assess definite eligibility for inclusion. Effect measures are reported as odds ratios (OR) or weighted mean difference (WMD) with 95% confidence intervals (95%-CI).

Main results: 

Eleven randomized controlled studies including a total of 984 participants undergoing on- or off-pump cardiac surgical procedures were identified. Pooled analysis showed that statin pre-treatment before surgery reduced the incidence of post-operative atrial fibrillation (AF) (OR 0.40; 95%-CI: 0.29 to 0.55; p<0.01), but failed to influence short-term mortality (OR 0.98, 95%-CI: 0.14 to 7.10; p=0.98) or post-operative stroke (OR 0.70, 95%-CI: 0.14 to 3.63; p=0.67). In addition, statin therapy was associated with a shorter length of stay of patients on the intensive care unit (ICU) (WMD: -3.39 hours; 95%-CI: -5.77 to -1.01) and in-hospital (WMD: -0.48 days; 95%-CI: -0.85 to -0.11) where significant heterogeneity was observed. There was no reduction in myocardial infarction (OR 0.52; 95%-CI: 0.2. to 1.30) or renal failure (OR 0.41; 95%-CI: 0.15 to 1.12). These results were unaffected after subgroup analysis. No major or minor perioperative statin side-effects were reported from trials investigating this safety endpoint.