Perioperative statins: More than lipid-lowering?
ABSTRACTPreliminary evidence indicates that statin drugs may be beneficial when given in the perioperative period. Although more studies are needed to draw firm conclusions, the acute nonlipid pleiotropic effects of statins may improve patient outcomes, especially for patients at the highest risk.
KEY POINTS
- Experiments in animals suggest that statins, given shortly before or after a cardiovascular event, confer benefit before any changes in lipids are measurable.
- Retrospective and prospective studies indicate that patients with either acute myocardial infarction or acute coronary syndrome who are already receiving statins should not have them stopped, and those who had not been receiving statins should receive them immediately.
- Most patients undergoing coronary artery bypass grafting or noncardiac vascular surgery should already be receiving a statin. These drugs can also be considered in patients undergoing intermediate-risk nonvascular surgery. Patients who have been receiving statins prior to surgery should not have them stopped for surgery.
Carotid endarterectomy
Two recent retrospective cohort studies evaluated the outcomes in patients undergoing carotid endarterectomy.19,20
Kennedy et al19 found that patients on a statin at the time of admission who had symptomatic carotid disease had lower rates of inhospital death (adjusted odds ratio 0.24, 95% CI 0.06–0.91) and ischemic stroke or death (adjusted odds ratio 0.55, 95% CI 0.31–0.97). However, cardiac outcomes among these symptomatic patients were not significantly improved (odds ratio 0.82, 95% CI 0.45–1.50), nor was there benefit for asymptomatic patients, raising the possibility that the positive findings were due to chance or that patients at lower baseline risk for vascular events may have less benefit.
McGirt et al20 performed a similar study; they did not, however, distinguish whether patients had symptomatic vs asymptomatic carotid disease. The 30-day risk of perioperative stroke was lower in patients treated with a statin, with an odds ratio of 0.41 (95% CI 0.18–0.93); the odds ratio for death was 0.21 (95% CI 0.05–0.96). Cardiac outcomes were not significantly affected.
Coronary artery bypass graft surgery
According to the NCEP recommendations, nearly all patients undergoing CABG should already be on a statin before surgery since they all have known coronary artery disease. Multiple observational studies have offered confirmatory evidence that statins are beneficial in this setting.34–38
Liakopoulos et al39 evaluated whether the anti-inflammatory effects of statins may, in part, account for their beneficial effect in the perioperative period. The authors prospectively matched 18 patients who were taking statins and were referred for elective CABG with 18 patients who were not prescribed statins previously. The only major measured baseline characteristic that differed between the two groups was a statistically significantly lower LDL-C level in the statin group. The operative characteristics did not differ, and cytokine levels at baseline were similar.
Tumor necrosis factor alpha levels increased significantly in the control group but did not change significantly in the statin group. Interleukin 8 increased in both groups by a similar amount. Interleukin 6 (the major inducer of C-reactive protein) increased from baseline in both groups but did not increase nearly as much in the statin group as in the control group; the intergroup difference was statistically significant. The anti-inflammatory cytokine interleukin 10 increased minimally from baseline in the control group, while the statin group’s levels increased significantly above baseline and those of the control group.
Christenson40 also found that inflammatory markers were improved with pre-CABG statin treatment in a small randomized trial in which patients received simvastatin 20 mg 4 weeks prior to CABG surgery vs no statin. Interestingly, far fewer statin-treated patients developed thrombocytosis (platelet count > 400 × 109/L) than did control patients (3% vs 81%, P < .0001).
RISKS OF PERIOPERATIVE STATINS
The risks associated with statin therapy in general appear low, but specific perioperative risks have not been well studied.
Baigent et al,41 in a meta-analysis of randomized trials of nonperioperative statin therapy, found that rhabdomyolysis occurred in 9 (0.023%) of 39,884 patients receiving statins vs 6 (0.015%) of the 39,817 controls, with a number needed to harm of 12,500. Moreover, the rates of nonvascular death and cancer did not increase. It is plausible that the risk is somewhat greater in the perioperative setting but is likely not enough to outweigh the potential benefits, especially since the risk of ischemic vascular events is particularly high then.
Some of the perioperative studies cited above specifically addressed potential risks. For example, in the study by Schouten et al,32 mild creatine kinase elevations were more common in the statin-treated group, but the incidence of moderate and severe creatine kinase elevations did not differ significantly. No case of rhabdomyolysis occurred, and length of surgery was the only predictor of myopathy. MIRACL and PROVE-IT revealed similar safety profiles; aminotransferase levels normalized when statins were stopped, and no cases of rhabdomyolysis occurred.11,12 In the vascular surgery study by Durazzo et al,23 1 (2%) of the 50 atorvastatin-treated patients developed both rhabdomyolysis and elevated aminotransferase levels that prompted discontinuation of the statin.
Overall, the observational studies do not indicate that statin continuation or treatment is harmful in perioperative patients. However, these studies did not specifically evaluate patients with acute insults from surgery such as sepsis, renal failure, or hepatitis. It is unknown what effect statin therapy would have in those patients and whether statins should be selectively discontinued in patients who develop major hepatic, musculoskeletal, or renal complications after surgery.
