Statins are widely prescribed cholesterol-lowering agents that inhibit the actions of 3-hydroxy-3-methylglutaryl coenzyme A reductase.¹ Because of the modulatory effects of statins on the atherogenic lipid profile, the role of statin therapy is expanding amid the growing obesity epidemic. Because the serum cholesterol level is strongly associated with coronary heart disease, it has been generally assumed that the beneficial effects underlying statin therapy entirely results from cholesterol reduction. The cholesterol-lowering effects of statin therapy remain central to the longterm management of coronary artery disease and cerebrovascular disease.

Statin pleiotropy is still an evolving concept and clinical studies have yet to show how many of the benefits of the statins are non-low-density lipoprotein (non-LDL) dependent.² The vascular protective effect of the statins is primarily mediated by inhibiting the mevalonate pathway and the generation of oxidized LDL; thereby, enhancing the biosynthesis of endothelium-derived nitric oxide. With the molecular insights obtained from basic studies regarding isoprenoid synthesis and the inhibition of the Rho/Rho-associated protein kinase (Rho/ROCK) pathway and the Rac pathway, it may be possible in the near future to actually define the clinical benefits of statin therapy that is attributable to non-LDL effects.³

Despite advances in surgical techniques and medical management, cardiovascular complications remain the most common cause of postoperative morbidity and mortality in patients undergoing noncardiac surgery. Patients with perioperative myocardial infarctions (MI) have an in-hospital mortality of 15–25%. The pathophysiology of perioperative MI is complex. It can be related to a myocardial oxygen demand/supply mismatch precipitated by perioperative surgical stress, tachycardia, hypertension, and pain.4, 5 Accumulating clinical evidence strongly suggests that administration of statins would reduce overall mortality, the development myocardial infarction and atrial fibrillation, and the length of hospital stay after major cardiac and noncardiac surgery.⁶

In surgical patients, retrospective studies strongly suggest the utility of perioperative statin therapy, although it is probably overestimated since important confounding factors were not controlled. Hence, the literature is considered inconclusive. Several recent statin trials in patients with low or normal cholesterol levels have suggested additional benefits beyond cholesterol lowering. These cholesterol-independent effects include improving endothelial function, attenuating vascular and myocardial remodeling, inhibiting vascular inflammation and oxidation, and stabilizing atherosclerotic plaques.² According to large clinical trials, the administration of statin appears safe; however, there is a small risk of an excessive elevation in the hepatic transaminase level.⁷ However, anesthetists and anesthesiologists should be aware that the most common adverse events related to statin therapy are myopathy, rhabdomyolysis, and elevated liver enzymes. Patients with advanced age (older than 80 years), small body frame, coexistent chronic diseases such as chronic renal failure and severe liver impairment, multiple medications, and chronic alcoholism have an increased risk of developing statin-related adverse effects. Recommendations concerning appropriate dosing, duration, therapeutic targets, and necessary investigations when prescribing perioperative statins should be addressed in a future study.

Statins in the perioperative period may be associated with a reduction in cardiovascular end points and mortality in patients undergoing intermediate-risk noncardiac, nonvascular surgery. Beyond cardiac risk reduction, statin therapy also may protect the brain and the kidney in the perioperative setting in patients undergoing cardiac or vascular surgeries. The pleiotropic effects of the statins also appear to have therapeutic roles in the progression of valve disease, sepsis, and venous thrombosis. Further trials are required to provide data to encourage their safe and comprehensive perioperative application for optimal short term and the longterm patient outcome.

The perioperative drug–drug interactions with statins should be considered during anesthetic management. Statins may interact with a wide array of medicines or compounds at the pharmacokinetic level, particularly during drug transformation in the liver.¹ The concurrent administration of statins with CYP450 inhibitors may thus elevate the blood concentration of statins and increase the risk of toxicity. The most common concern about the perioperative use of statins is administering it in combination with succinylcholine, which could be deleterious by causing muscle injury.⁴However, a study by Biccard⁵ concluded that the effect of succinylcholine administered to patients taking statins was likely small and probably of limited clinical consequence. In clinical practice, adverse responses resulting from perioperative drug interaction with statins are probably overlooked, but anesthesiologists and anesthetists should be aware that statin-induced muscle and hepatic toxicity could be amplified in high-risk patients.

The optimal dose and treatment period for the perioperative administration of statins are still under debate. Dose-ranging and time-course studies are necessary to provide more accurate use of different statins during the perioperative period. In addition, more clinical evidence is required to support the use of statins as part of the acute phase therapy before a major operation. Since surgical patients have most likely experienced a prolonged fasting period before and after a major operation, the development of parenteral preparations for statins would be highly desirable to enhance the bioavailability of perioperative statin delivery. It is clear that the mechanisms responsible for the tissue-protective effects of statins are pleiotropic and multifactorial. In clinical settings, the evidence concerning the exclusive vascular protection of statins (independent from their lipid-lowering property) is relatively insufficient since the therapeutic indications of statins usually do not include vascular protection. Clinical studies investigating the pleiotropic effects of statins in patients without dyslipidemia are therefore warranted to extend their clinical applications.

In conclusion, besides their lipid-lowering property, statins mediate important pleiotropic effects in vascular protection and this may be applicable to other systemic organs (e.g., renal, neurological, and psychosomatic systems) during the perioperative period. Perioperative statin use reduces overall mortality, the development myocardial infarction and atrial fibrillation, and the length of the hospital stay after major cardiac and noncardiac surgery. Patients who are taking long-term statin therapy should continue the treatment perioperatively since discontinuation of statins may result in adverse cardiovascular events. The perioperative use of statins is generally well tolerated, but attention should be paid to patients of old age, small body size, and advanced stage comorbidities. It is hoped that this review will encourage further study, especially research elucidating which anesthetics may be more suitable and safer in regard to vascular protection.