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Anesthesiology:
doi: 10.1097/ALN.0b013e3181a961be
Correspondence

Perioperative Statin Therapy May Be Implicated in a Wide Array of Drug-Drug Interactions

Manach, Yannick Le M.D.*; Coriat, Pierre M.D.; Collard, Charles D. M.D.; Riedel, Bernhard M.D., Ph.D.

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In Reply:—

We appreciate the valuable commentary provided by Marcucci et al. in response to our recent article on perioperative statin therapy.1
The data supporting the efficacy and relative safety of statin therapy in the nonsurgical population continues to increase.2 Statin-induced myopathy most often accompanies chronic statin therapy in patients receiving multiple concurrent medications. The perioperative period, characteristically associated with acute administration of a multitude of medications and with hemodynamic perturbation, increases the potential for drug-drug interactions with statin therapy and for altered clearance of statins. Thus, Marcucci et al. rightly point out that concurrent medication administration in the perioperative period might alter statin plasma levels via the hepatic cytochrome P450 system or other adverse drug-drug interactions, with an implication of either a reduced therapeutic effect3 or increased risk of adverse effects.4,5
However, despite the theoretical concern of Marcucci and colleagues, reported adverse effects associated with perioperative statin therapy are extremely rare.6 We consider that the clinical relevance of these drug-drug interactions to be largely theoretical as, to the best of our knowledge, no large studies have reported considerably morbidity associated with continued statin therapy in the perioperative period, and is contrary to the unreferenced implication by Marcucci et al.
Marcucci et al., however, reiterate a valuable point that should be considered in the daily practice of caring for the perioperative and critically ill patient—that of being aware of potential drug-drug interactions. Marcucci et al. provide a valuable reference against which to check the potential for drug interactions. This may also have increasing relevance in patients being exposed acutely to high-dose statin therapy—especially as we see increasing literature support a protective effect of statin therapy introduced acutely in the preoperative period.
Finally, in the absence of a large cohort reporting significant statin-associated morbidity, we feel confident that the current risk-benefit ratio strongly favors the continued administration of perioperative statins in patients who otherwise have no other contraindications to statin therapy because of their proven protective effects on adverse postoperative outcomes.
Yannick Le Manach, M.D.*
Pierre Coriat, M.D.
Charles D. Collard, M.D.
Bernhard Riedel, M.D., Ph.D.
*Groupe Hospitalier Pitié-Salpêtrière, Paris, France. yannick.le-manach@psl.ap-hop-paris.fr
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References

1. Le Manach Y, Coriat P, Collard CD, Riedel B: Statin therapy within the perioperative period. Anesthesiology 2008; 108:1141–6

2. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ: Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359:2195–207

3. Le Manach Y, Godet G, Coriat P, Martinon C, Bertrand M, Fleron MH, Riou B: The impact of postoperative discontinuation or continuation of chronic statin therapy on cardiac outcome after major vascular surgery. Anesth Analg 2007; 104:1326–33

4. Bellosta S, Paoletti R, Corsini A: Safety of statins: Focus on clinical pharmacokinetics and drug interactions. Circulation 2004; 109:III50–7

5. Thompson PD, Clarkson P, Karas RH: Statin-associated myopathy. JAMA 2003; 289:1681–90

6. Schouten O, Kertai MD, Bax JJ, Durazzo AE, Biagini E, Boersma E, van Waning VH, Lameris TW, van Sambeek MR, Poldermans D: Safety of perioperative statin use in high-risk patients undergoing major vascular surgery. Am J Cardiol 2005; 95:658–60

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