In 2002, a public health advisory released by the American Heart Association (AHA) advised that patients taking statins, the most common class of drugs used to treat high cholesterol, temporarily discontinue their statin therapies during the perioperative period to help prevent the risk of renal failure (1). This advice was swiftly accepted and affixed to the labels of statin medications. However, only thirteen years later, the American Society of Anesthesiologists (ASA) released a pressing news statement concerning the discontinuation of statins for surgical patients: as a study of more than 300,000 patients indicated, patients who undergo surgery while discontinuing their statin therapies and do not resume their medication within two days have a higher risk of death. Fortunately, the instructions of the 2002 AHA advisory had not yet made its way into common practice; this was partly because, in 2007, the American College of Cardiology (ACC) and the AHA noted that statins helped reduce inflammation and promote blood flow and began recommending against the perioperative interruption of statin therapies. However, many physicians were still adhering to the original AHA health advisory (2).

A correction to the AHA’s public health advisory has since been published to reflect the findings reported by the ASA (3). Nonetheless, it still remains the case that high cholesterol presents a significant risk factor to patients undergoing surgical procedures. Aside from increasing the risk of post-operative complications in some cases (4), high cholesterol levels may also result in the delayed action of propofol, a commonly used anesthetic (5,6). An important question to address, then, is how best to mitigate these perioperative risk factors for high cholesterol patients and what role, if any, statins can play in that process.

In the years following the ASA press release, it has been suggested that patients who were not previously on statins, even those with normal cholesterol levels, could receive perioperative statin therapy to reduce their risk of post-operative cardiovascular complications (7). Although some clinical trials have suggested a greater focus on such complications (8,9), Zheng et al.’s larger-scale study in 2017 found that patients undergoing elective heart surgery did not show a significant reduction in the risk of post-operative atrial fibrillation or perioperative myocardial damage and in fact appeared to have a higher risk for acute renal injury. This study also found that patients who had already been taking statin medications did not seem to show a greater risk of post-operative complications when they discontinued their statin therapies for their surgeries, at odds with the conclusions the ASA had arrived at in 2015 (10).

Even more perplexingly, a 2016 clinical study found that hyperlipidemia acted as a protective factor against intraoperative awareness during cardiac surgical procedures, in which there is a relatively higher risk of accidental awareness under anesthesia (11). This appears to conflict with the findings of the propofol case study as well as with those of Hantal et al.’s study of the effect of general anesthetics on the properties of lipid membranes, in which the authors determined that cholesterol had the opposite effect on these membranes from that of general anesthetics and that general anesthetics had a greater effect on membrane domains with lower levels of cholesterol (12). With the connections between cholesterol levels, statins, and perioperative risks not yet entirely clear, the one consensus appears to be that patients taking statins to prevent cardiovascular events should restart their statin therapy as soon as safely possible after a surgical procedure, if it was interrupted for the sake of the operation (2,3).

References

(1) Pasternak, R. C.; Smith, S. C.; Bairey-Merz, C. N.; et al. ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. Circulation 2002, 106 (8), 1024–1028. https://doi.org/10.1161/01.CIR.0000032466.44170.44.

(2) American Society of Anesthesiologists. Surgical Patients Should Stay on Cholesterol Medications to Reduce Risk of Death, Study Shows. October 27, 2015. https://www.asahq.org/about-asa/newsroom/news-releases/2015/10/surgical-patients-should-stay-on-cholesterol-medications.

(3) Newman, C. B.; Preiss, D.; Tobert, J. A.; et al.; on behalf of the American Heart Association. Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arterioscler. Thromb. Vasc. Biol. 2019, 39 (2). https://doi.org/10.1161/ATV.0000000000000073.

(4) Cancienne, J. M.; Brockmeier, S. F.; Rodeo, S. A.; Werner, B. C. Perioperative Serum Lipid Status and Statin Use Affect the Revision Surgery Rate After Arthroscopic Rotator Cuff Repair. Am. J. Sports Med. 2017, 45 (13), 2948–2954. https://doi.org/10.1177/0363546517717686.

(5) Johnson, T. J.; Porhomayon, J.; Nader, N. D.; et al. Hyperlipidemia Sink for Anesthetic Agents. J. Clin. Anesth. 2016, 34, 436–438. https://doi.org/10.1016/j.jclinane.2016.05.022.

(6) Folino, T. B.; Muco, E.; Safadi, A. O.; Parks, L. J. Propofol. In StatPearls; StatPearls Publishing: Treasure Island (FL), 2020.

(7) Tereshina, O. V.; Vachev, A. N.; Frolova, E. V. [Perioperative use of statins in vascular surgery]. Angiol. Vasc. Surg. 2016, 22 (1), 11–21. https://pubmed.ncbi.nlm.nih.gov/27100533/.

(8) Li, M.; Zou, H.; Xu, G. The Prevention of Statins against AKI and Mortality Following Cardiac Surgery: A Meta-Analysis. Int. J. Cardiol. 2016, 222, 260–266. https://doi.org/10.1016/j.ijcard.2016.07.173.

(9) Omar, A. S.; Hanoura, S.; Al-Janubi, H. M.; Mahfouz, A. Statins in Critical Care: To Give or Not to Give? Minerva Anestesiol. 2017, 83 (5), 502–511. https://doi.org/10.23736/S0375-9393.16.11493-2.

(10) Zheng, Z.; Jayaram, R.; Jiang, L.; et al. Perioperative Rosuvastatin in Cardiac Surgery. N. Engl. J. Med. 2016, 374 (18), 1744–1753. https://doi.org/10.1056/NEJMoa1507750.

(11) Zheng, Q.; Wang, Q.; Wu, C.; Wang, Z.; Ao, H. Is Hyperlipidemia a Potential Protective Factor against Intraoperative Awareness in Cardiac Surgery? J. Cardiothorac. Surg. 2016, 11 (1), 60. https://doi.org/10.1186/s13019-016-0454-7.

(12) Hantal, G.; Fábián, B.; Sega, M.; Jójárt, B.; Jedlovsky, P. Effect of General Anesthetics on the Properties of Lipid Membranes of Various Compositions. Biochim. Biophys. Acta Biomembr. 2019, 1861 (3), 594–609. https://doi.org/10.1016/j.bbamem.2018.12.008.