Effect of Lipid-lowering Medications in Patients With Coronary Artery Bypass Grafting Surgery Outcomes

Discussion

This study demonstrated that preoperative lipid-lowering medication use was associated with decreased overall in-hospital complications especially neurologic complications, and lower mortality in elderly patients undergoing CABG with CPB. Postoperative lipid-lowering medication use was shown to be associated with improved long-term survival more than 5 years in the same patient population.

Statins are one of the most important therapies for patients with atherosclerotic coronary artery disease.^[19] In this study, 97.2% of the patients receiving lipid-lowering medications were receiving statins. Previous studies have reported that statin pretreatment in patients undergoing CABG could reduce postoperative mortality, MI, stroke, AF, and length of hospital stay.^[20] A multicenter prospective study of 5,436 patients undergoing CABG surgery indicated that perioperative statin therapy was independently associated with a significant reduction in the risk of early cardiac death after primary elective CABG surgery.^[21] Another study of patients undergoing CABG with CPB also provided evidence that preoperative statin therapy reduces the risk of early mortality.^[22] However, most of these studies only included the patients undergoing isolated CABG surgery. In order to assess the impact of lipid-lowering medications on a broader patient population, our study included both isolated CABG surgery and also CABG combined with other cardiac procedures. We found that neurologic complications (including stroke), in-hospital mortality and overall mortality were all reduced significantly in the patients treated with lipid-lowering medications.

In studies examining statin therapy and postoperative outcome in patients who underwent non-emergent valve surgery, the authors found that preoperative statin therapy was associated with significantly reduced mortality.^[23,24] We found statins were associated with reduced postoperative complications in patients undergoing CABG with or without other procedures suggesting that the beneficial effects from the combination of lipid-lowering, pleiotropic, anti-inflammatory, immunomodulatory, and antioxidant properties^[25–27] can benefit patients undergoing combined procedures as well. Statins inhibit the production of several proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), Interleukin-6 (IL-6), and IL-8, resulting in the reduction of C-reactive protein levels and suppression of natural killer cells.^[28–30] A meta-analysis including 10 cohort studies with a total of 147,263 participants showed that statin use was associated with a lower incidence of postoperative infectious complications in both cardiac and non-cardiac surgery possibly due to anti-inflammatory or immunomodulatory properties.^[10] Another study showed that male gender, increased BMI, presence of left main coronary artery disease, and increased LOS were significantly associated with the risk of deep sternal wound infections, while the presence of hypercholesterolemia was a protective factor hypothesized to be due to long-term statin use.^[31] Although studies have demonstrated statin therapy was associated with a reduced risk of postoperative infection,^[10,31,32] other studies including the present one did not support this finding.^[33,34]

Similarly, there is a high incidence of AKI after cardiac surgery which is associated with increased postoperative mortality and hospital costs.^[35] The effect of statin on AKI and perioperative renal replacement therapy is another controversial topic. Some clinical studies have shown positive renal protection in patients using statins undergoing cardiac surgery.^[13,36,37] However, other studies did not reach the same conclusion.^{[20,38,39,40]} Our study found perioperative statin therapy was not associated with a reduced incidence of cardiac surgery-associated AKI.

Postoperative atrial fibrillation (POAF) is one the most frequent complications after cardiac surgery, and the role of statin use in preventing POAF has been extensively studied. POAF is triggered by the interaction of different pathogenic factors and inflammatory processes. Sulzgruber and colleagues suggested that preoperative statin therapy decreased the development of POAF due to anti-inflammatory properties, such as reducing the level of C-reactive protein (CRP).^[41] It has also been suggested that statin therapy has an overall protective effect against POAF especially in patients undergoing CABG.^[9] We did not find statin therapy is protective against POAF in this study.

Postoperative stroke in cardiac surgery patients increases morbidity and mortality.^[42,43] Evidence has shown that statins can exert multidirectional effects, interfering with reactive oxygen species development, clot formation, endothelial function, and brain plasticity which might play an essential role in the treatment of ischemic stroke, preventing stroke recurrence and cardiovascular events, and improving functional performance.^[44] Another study also confirmed the effect of statin-based therapy for primary and secondary prevention of ischemic stroke.^[45] Our results show preoperative lipid-lowering treatment was associated with reduced postoperative stroke and other neurologic complications which supports a neuroprotective effect of statins following CABG.

The results from the present study show that patients on lipid-lowering medications postoperatively had a longer postoperative survival time, suggesting that lipid-lowering medications could reduce postoperative mortality after cardiac surgery for one year or longer. This is consistent with findings shown by others and it is suggested that the anti-inflammatory effect of statin could be one of the mechanisms.^[46–48] Another study in patients with atherosclerotic cardiovascular disease evaluated major adverse cardiac events (MACE) defined as MI, angina, coronary revascularization, ischemic stroke, transient ischemic attack (TIA), or peripheral artery disease. The results indicated that statin use within 30 days of hospital discharge was associated with a lower risk of MACE.^[49]

This study has several limitations. First, it is a retrospective, nonrandomized study with potential hidden biases that could have affected our analysis. Second, we knew whether patients were receiving perioperative statin treatment, but we were unable to classify the types, doses, and timing of statin therapy. Lastly, compared to non-LLT patients, patients with lipid-lowering therapy were more likely to be concomitantly treated with aspirin, β-blockers, ACEI or ARB which could have beneficial effects on postoperative outcomes,^[50] but were also more likely to have comorbid conditions that could have negative effects on postoperative outcomes. Although we have taken these factors into account in our statistical analysis, they may still have confounding effects.

In conclusion, among patients undergoing CABG with CPB, perioperative statin use was associated with reduction of postoperative complications and mortality. Postoperative lipid-lowering medication use was shown to be associated with improved 5-year long-term survival. Our study suggests that patients undergoing CABG should consider starting statin therapy perioperatively unless contraindicated, especially for those with significant risk factors such as atherosclerotic cardiovascular disease.

BMC Anesthesiol. 2022;22(122) © 2022 BioMed Central, Ltd.