The use of statins is widespread and many patients presenting for surgery are regularly taking them. There is evidence that statins have beneficial effects beyond those of lipid lowering, including reducing the perioperative risk of cardiac complications and sepsis. This review addresses the cellular mechanisms by which statins may produce these effects. Statins appear to have actions on vascular nitric oxide through the balance of inducible and endothelial nitric oxide synthase. The clinical evidence for these benefits is also briefly reviewed with the objective of clarifying the current status of statin use in the perioperative period. There is reasonably strong evidence that patients already taking statins should continue on them perioperatively. However, the evidence for the prophylactic use of statins perioperatively is weak and lacks prospective controlled studies.
◊ Reviewed by J. Raeder, MD, PhD
Chairman of Clinical Ambulatory anaesthesia / Professor in Anaesthesiology,
Dept. of Anaesthesia, Oslo University Hospital, Oslo, Norway
This is a well written review finalized in the first half of 2009 by authors doing microcirculatory research. The potential role of statins in perioperative medicine is interesting, complicated, and under debate. At least three major approaches have been undertaken in order to elucidate that role: (1) What are the basic mechanisms on a cellular and biochemical level? (2) What are the resulting physiological effects after taking interactions with other cellular mechanisms into account? (3) What are the observed clinical effects and outcomes?
The paper is basically discussing research done on the first two questions, discriminating between effects relevant to lowering lipids and anti-inflammatory effects. The latter were further differentiated by actions on endothelium, atherosclerosis, arrythmia and during septicaemia. The authors also present a brief (in their own words) review of the literature on clinical evidence.
The presentation of basic mechanisms seems to be comprehensive, well structured, and very useful for someone not being an expert in this field. The conclusion seems to be that although there might be a lot of basically beneficial effects of statins in the perioperative setting, no clear-cut clinical recommendations can be made based on available basic research. Thus, it is mandatory to use this basic knowledge in well designed clinical studies to look at the clinical relevance. Although most of the clinical studies published until early 2009 were included in the discussion, the authors obviously have missed most recent ones in this area of topical interest with a lot of studies going on. Nevertheless, there seems to be common agreement and strong supporting evidence that patients already treated with statins should continue those perioperatively. However, from my reading of recent papers the authors’ conclusion of “weak evidence for initiating prophylactic perioperative statin use” may be challenged.
There are recent placebo-controlled studies which have also demonstrated less delirium with perioperative statins [1] and less proliferation of advanced mamma cancer [2]. A recent placebo-controlled study of 497 patients undergoing elective vascular surgery also demonstrated less coronary complications and even lower mortality in patients starting fluvastatin 37 days (mean) prior to surgery [3]. Based on this and other data, some recent reviews recommended starting statins preoperatively in patients scheduled for vascular surgery and cardiovascular bypass surgery [4-7]. However, to my knowledge this has not yet entered into official evidence-based recommendations of national or international bodies. It is under discussion whether for these types of surgery all or only high-risk patients should start taking statins beforehand, let alone future discussions of what might be the criteria for a high-risk patient. This has to be viewed also from an economic and more importantly from a safety perspective given that there are very rare but serious complications of myopathy and liver failure. The indication for using a drug should be sound as there is always a risk of side effects. Further questions which have not been answered yet in the context of making approved recommendations: Would all statins be equally suitable? Which dose would be appropriate? When should treatment start and end?
To me it seems like the final decision is still pending, but evidence to support initiation of preoperative statin treatment in at least some risk patients becomes stronger and stronger. To urge patients who are already on statins to continue those seems to be common agreement already.
◊ References
[1] Garwood ER, Kumar AS, Baehner FL, Moore DH, Au A, Hylton N, Flowers CI, Garber J, Lesnikoski BA, Hwang ES, Olopade O, Port ER, Campbell M, Esserman LJ: Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer. Breast Cancer Res.Treat. 2010; 119: 137-44
[2] Katznelson R, Djaiani G, Mitsakakis N, Lindsay TF, Tait G, Friedman Z, Wasowicz M, Beattie WS: Delirium following vascular surgery: increased incidence with preoperative beta-blocker administration. Can.J.Anaesth. 2009; 56: 793-801
[3] Schouten O, Boersma E, Hoeks SE, Benner R, van UH, van Sambeek MR, Verhagen HJ, Khan NA, Dunkelgrun M, Bax JJ, Poldermans D: Fluvastatin and perioperative events in patients undergoing vascular surgery. N.Engl.J.Med. 2009; 361: 980-9
[4] Bauer SM, Cayne NS, Veith FJ: New developments in the preoperative evaluation and perioperative management of coronary artery disease in patients undergoing vascular surgery. J.Vasc.Surg. 2009; E-pub ahead of printing.
[5] Poldermans D: Statins and noncardiac surgery: current evidence and practical considerations. Cleve.Clin.J.Med. 2009; 76 Suppl 4: S79-S83
[6] Bagry HS, Carli F: Role of statins in peri-operative medicine. Curr.Drug Targets. 2009; 10: 850-7
[7] Kulik A, Ruel M: Statins and coronary artery bypass graft surgery: preoperative and postoperative efficacy and safety. Expert.Opin.Drug Saf 2009; 8: 559-71
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