Anti-inflammatory effects of perioperative statin therapy

Perioperative physicians seek to reduce the risk of adverse perioperative events, focusing in particular on adverse cardiovascular events such as myocardial infarction (MI) and cardiac death. To this aim, extensive and often invasive intraand postoperative hemodynamic monitoring have become the standard of care. Obviously, monitoring in itself does not prevent adverse events as over 5% of highrisk surgical patients still suffer from perioperative myocardial ischemia and infarction. Therefore, efforts have been undertaken to reduce the risk of perioperative MI by risk stratification during preoperative assessment and subsequent initiation of preventive medical treatment early before surgery in patients identified as high-risk. Preventive medical treatments that have been investigated include preoperative initiation of beta-blockers, alpha2agonists, acetylsalicylic acid, and statins. The effect of initiating prophylactic treatment with beta-blockers to reduce perioperative MI seems counterbalanced by the occurrence of other major adverse events, such as stroke and death. The results of studies evaluating perioperative prophylactic treatment of high-risk patients with acetylsalicylic acid and alpha2-agonists seem encouraging, but current evidence is insufficient to advocate their widespread use. Statins were considered another promising class of drugs in the prevention of perioperative MI among high-risk surgical patients with cardiovascular risk factors. Since the mid-1990s, when the results of the Scandinavian Simvastatin Survival Study (4S) were published, statins have become a cornerstone in the secondary prevention of cardiovascular disease. Statins are particularly recommended for those patients with cardiovascular disease who do not meet the lipid-lowering goals through lifestyle approaches, as statins effectively lower cholesterol levels and decrease mortality by decreasing the incidence of MI and stroke. Beyond lipid-lowering activity in the prevention of atherosclerosis, statins exhibit action by improving vascular endothelial function, modulating inflammatory responses, and maintaining plaque stability, thereby preventing thrombus formation. These so-called ‘‘pleiotropic’’ effects of statins are believed to occur within 24 hr after statin initiation and prior to the reduction in serum cholesterol levels (weeks). The rapid onset of the pleiotropic effects was considered potentially useful to prevent perioperative MI, as plaque instability / disruption, most likely associated with perioperative inflammation, has been recognized as a relevant cause of MI that is potentially responsible for up to 50% of perioperative MIs. If statin therapy can effectively diminish the inflammatory response to surgical trauma, a perioperative MI might be prevented. This effect would be comparable with maintaining plaque stability after acute coronary syndrome in the nonsurgical setting. Several retrospective and nonrandomized studies showed that statin use is indeed associated with reduced mortality. A small number of randomized clinical trials examining the effect of statins on cardiovascular outcome after noncardiac surgery have been published. In 2004, Durazzo et al. reported a threefold reduction (from 26% to 8%) in the occurrence of an adverse cardiovascular event or death within six months after surgery in a high-risk population of 100 patients undergoing vascular surgery. In this trial, patients were given atorvastatin or placebo for an average of 30 days before surgery. The DECREASE III W. A. van Klei, MD, PhD (&) W. F. Buhre, MD Division of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center Utrecht, Local Mail Q04.2.313, PO Box 85500, 3508 GA Utrecht, The Netherlands e-mail: [email protected]