Perioperative statin therapy has long been felt to confer cardiac protection during both cardiac surgery and major noncardiac surgery. Until recently the data have been scarce to definitively make claims in support of this belief. In 2004, Durazzo et al. conducted the first randomized trial examining the use of Perioperative statins in major noncardiac surgery. They compared the use of atorvastatin 20 mg daily compared against placebo initiated 2 weeks prior to elective major vascular surgery and continued for 45 days post-operatively. The investigators found that statins were associated with a 70% relative risk reduction of the combined end-point of death, nonfatal MI, unstable angina, or stroke. [1] Prior to this in 1999, Christenson had demonstrated cardioprotective effects of statins during coronary artery bypass grafting surgery. [2]
Statins are thought to be beneficial for a myriad reasons:
They lower lipids and have additional pleiotropic effects.
The cardioprotective effects of statins during the perioperative period is more likely related to their pleiotropic effects than their lipid-lowering effects.
Statins inhibit the action of HMG-CoA Reductase which is the rate-limiting step in cholesterol synthesis, but effective lipid lowering takes months.
Perioperative studies have demonstrated that statins confer a cardioprotective benefit when started even 1-2 weeks in advance of major surgery.
These pleiotropic effects of statins include suppression of endothelial nitric oxide which promotes coronary vasodilation.
Statins also reduce lipopolysaccharide-induced tissue factor release, decrease plasminogen activator inhibitor levels, and increase tissue plasminogen activator; the combination of which reduces coronary thrombosis.
Statins also have anti-inflammatory properties which may provide more plaque stability. [3]
A new systematic review and meta-analysis published this year examined the efficacy of perioperative statins in statin-naïve patients undergoing cardiac or major noncardiac surgery. The review analyzed 2292 patients from fifteen randomized controlled studies. Seventy five percent of the trials involved cardiac surgery, but there were four randomized controlled trials examining the benefit of statins in major noncardiac surgery. [4]
This systematic review found that statins decreased the risk of atrial fibrillation, myocardial infarction, and hospital length of stay when started preoperatively and continued postoperatively. Specifically, statins reduced the risk of atrial fibrillation after CABG (RR 0.56, CI 0.45-0.69, number needed to treat = 6). Statins also reduced the risk of myocardial infarction in both cardiac and major noncardiac surgery (RR 0.53, CI 0.38-0.74, NNT = 23). Finally, statins were associated with a 33% reduction in the hospital length of stay. There was a trend towards decreased mortality, but this did not reach statistical significance. [4]
One study by Manach et al from France investigated the effect of postoperative discontinuation of chronic statins after major aortic surgery. They discovered that patients who resumed statin therapy within 24 hours of major aortic surgery had three-fold less myonecrosis compared to those patients who resumed statin therapy four days after surgery. [5] This suggests that prolonged withdrawal of statin therapy may cause a deleterious rebound effect.
We are constantly searching for ways to reduce perioperative mortality and morbidity. Perioperative beta-blockers have been shown to be cardioprotective for vascular surgery and major noncardiac surgery. Early administration of thromboprophylaxis after major surgery is warranted to prevent venous thromboembolism. Timely administration of preoperative antibiotics significantly decreases the incidence of surgical site infections. Now, this review provides good evidence that statins should be added to the armamentarium prior to CABG or major noncardiac surgery in statin-naïve patients. Additionally, statins should be resumed within 24 hours after the operation if at all possible.
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Joseph Esherick, MD, FAAFP is the Associate Director of Medicine and the Medical ICU Director at the Ventura County Medical Center in Ventura, California. He is also an Associate Clinical Professor of Family Medicine at The David Geffen School of Medicine at UCLA. He received his medical degree from Yale University School of Medicine, New Haven, Connecticut, and completed a family practice residency at the Ventura County Medical Center, Ventura, California. He is board certified in family medicine and the author of the Tarascon Primary Care Pocketbook and the Tarascon Hospital Medicine Pocketbook. He is one of the lead instructors of the Hospitalist and Emergency Procedures Courses for Hospital Procedures Consultants. He is also an editorial board member for Tarascon Publishing and for Elsevier’s First Consult.
Dr. Esherick is the author of some of Tarascon Publishing’s best-selling titles including: Tarascon Medical Procedures Pocketbook, Tarascon Hospital Medicine Pocketbook and Tarascon Primary Care Pocketbook. Hospital Medicine and Primary Care are also available for mobile (iPhone, Android and Blackberry).
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[1] Durazzo AE et al. Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial. J Vasc Surg, 2004; 39: 967-975. [2] Christenson JT. Preoperative lipid-control with simvastatin reduces the risk of postoperative thrombocytosis and thrombotic complications following CABG. Eur J Cardiothoracic Surg. 1999; 15 (4): 394-400. [3] Williams TM et al. Statins for Surgical Patients. Annals of Surgery, 2008; 247 (1): 30-37. [4] Chopra V et al. Effect of Perioperative Statins on Death, Myocardial Infarction, Atrial Fibrillation, and Length of Stay. Arch Surg, 2012; 147 (2): 181-189. [5] Manach YL et al. The Impact of Postoperative Discontinuation or Continuation of Chronic Statin Therapy on Cardiac Outcome After Major Vascular Surgery. Anesth Analg, 2007; 104: 1326-1333.