Physicians' Academy for Cardiovascular Education

A systemic review of existing evidence encourages pre-CABG statin therapy

Barakat AF, et al. Ann Thorac Surg 2016


Perioperative Statin Therapy for Patients Undergoing Coronary Artery Bypass Grafting


Barakat AF, Saad M, Abuzaid A, et al.
Ann Thorac Surg 2016;101:81825


Background

One of the reasons for the increased morbidity and mortality in patients undergoing coronary artery bypass grafting (CABG) is the development of an intense systemic inflammatory response in these patients, which is particularly profound when cardiopulmonary bypass is used [1-3].
Although there is evidence supporting a beneficial role of preoperative statin therapy in weakening this systemic inflammatory response [4,5], in everyday clinical practice, statin discontinuation before CABG is common, in order to avoid possible adverse effects [6].
The benefit of preoperative statin therapy is attributed to their pleiotropic effects that include:
  • Anti-inflammatory effect, measured by a significant reduction in serum levels of C-reactive protein [7,8]
  • Antithrombotic effect, as a result of the upregulation of nitric oxide, and the decreased production of thromboxane A2 and increased production of prostacyclin [9,10]
  • Antioxidant role, through the reduction in LDL oxidation [11]
  • Anti-proliferative effect on smooth muscle cells that contributes to the reduction of in-stent restenosis [12]
  • Reduction of atherosclerotic plaque neovascularization and macrophage content [13]
This article provides a review of the existing data on the role of perioperative statin therapy and its effect on postoperative outcomes in CABG patients.
 

Main results

There is clinical evidence supporting that preoperative statin therapy:
  • is associated with reductions of in-hospital mortality, operative mortality, and perioperative mortality
  • is an independent predictor of in-hospital mortality, particularly in high-risk patients
  • decreases the incidence of myocardial infarction after percutaneous coronary intervention and non-cardiac operations, but this effect was not proven in post-CABG patients (a statin reload strategy is currently tested, to recapture this effect)
  • is associated with reductions in risk of postoperative atrial fibrillation, if lipophilic statins are used, such as atorvastatin and simvastatin
  • is associated with a lower rate of perioperative cerebrovascular events, such as stroke or transient ischemic attack, although this evidence might reflect the decreased incidence of postoperative atrial fibrillation in the statin group of these studies
  • is associated with a decreased incidence of postoperative renal insufficiency, a reduced need for postoperative renal replacement therapy mainly in younger and low-risk patients, and a reduction in postoperative acute kidney injury, in observational studies using commercially available statins
  • is associated with a shorter mean duration of hospital stay after CABG, and a decrease in the length of intensive care unit stay, probably due to the reduction of postoperative complications
  • did not result in an increased risk of postoperative myopathy
 

Conclusion

Existing evidence supports the preoperative statin therapy in CABG patients, because it leads to improved postoperative outcomes, especially reduced perioperative mortality and atrial fibrillation. The risk for statin related adverse events in this setting of intense systemic inflammatory response is not increased.
 
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References

1. Hirai S. Systemic inflammatory response syndrome after cardiac surgery under cardiopulmonary bypass. Ann Thorac Cardiovasc Surg 2003;9:36570.
2. Warren OJ, Smith AJ, Alexiou C, et al. The inflammatory response to cardiopulmonary bypass: part 1—mechanisms of pathogenesis. J Cardiothorac Vasc Anesth 2009;23:22331.
3. MacCallum NS, Finney SJ, Gordon SE, et al. Modified criteria for the systemic inflammatory response syndrome (SIRS) improves their utility following cardiac surgery. Chest 2014;145:1197203.
4. Dereli Y, Ege E, Kurban S, et al. Pre-operative atorvastatin therapy to decrease the systemic inflammatory response after coronary artery bypass grafting. J Int Med Res 2008;36:124854.
5. Martínez-Comendador JMM, Alvarez JRR, Mosquera I, et al. Preoperative statin treatment reduces systemic inflammatory response and myocardial damage in cardiac surgery. Eur J Cardiothorac Surg 2009;36:9981005.
6. Filion KB, Pilote L, Rahme E, et al. Use of perioperative cardiac medical therapy among patients undergoing coronary artery bypass graft surgery. J Card Surg 2008;23:20915.
7. Albert MA, Danielson E, Rifai N, et al, PRINCE Investigators. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 2001;286:6470.
8. Plenge JK, Hernandez TL, Weil KM, et al. Simvastatin lowers C-reactive protein within 14 days: an effect independent of low-density lipoprotein cholesterol reduction. Circulation 2002;106:144752.
9. Notarbartolo A, Davì G, Averna M, et al. Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia. Arterioscler Thromb Vasc Biol 1995;15:24751.
10. Degraeve F, Bolla M, Blaie S, et al. Modulation of COX-2 expression by statins in human aortic smooth muscle cells. Involvement of geranylgeranylated proteins. J Biol Chem 2001;276:4684955.
11. Rikitake Y, Kawashima S, Takeshita S, et al. Anti-oxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits. Atherosclerosis 2001;154:8796.
12. Walter DH, Schachinger V, Elsner M, et al. Effect of statin therapy on restenosis after coronary stent implantation. Am J Cardiol 2000;85:9628.
13. Williams JK, Sukhova GK, Herrington DM, et al. Pravastatin has cholesterol-lowering independent effects on the artery wall of atherosclerotic monkeys. J Am Coll Cardiol 1998;31:68491.