In this large cohort of non-cardiac surgical patients, administration of statin medications in the peri-operative time period was associated with markedly reduced odds of developing clinically significant POAF. Though the absolute observed effect size was small (a 0.4% reduction in POAF), the at-risk pool of patients undergoing major non-cardiac surgery is very large. This modest risk reduction could drive relevant changes in health care cost and outcomes when applied to millions of patients annually. While statins’ effectiveness varied somewhat in patients using other cardiovascular medications concomitantly, the association between reduced odds of POAF and statin use was robust across a wide range of subgroups. Of note, statin treatment had no effect on outcomes among patients who did develop POAF. Whether statins’ effectiveness in reducing POAF is due to a direct anti-arrhythmic effect or mediated through reduced risk for other complications (such as myocardial infarction or infection) cannot be definitively discerned with our data.
The routine use of peri-operative medications to reduce adverse events has been an area of intense study for the past decade. The role of beta-blockers has been rapidly evolving, with recent literature suggesting no net clinical benefit (and perhaps harm) associated with the routine peri-operative administration of beta-blockers for non-cardiac surgery.21,22
Meanwhile, peri-operative statin use has garnered increasing interest as a preventive strategy. A large study by Lindenauer et al. suggested that statin use is associated with lower mortality in a population of patients undergoing major non-cardiac surgery.11
Additionally, statins have been shown prospectively to decrease cardiovascular complications following vascular surgery.12,23
Few data exist to describe the association between statin use and incidence of POAF in non-cardiac surgery, though statins have been shown to lower POAF risk in patients undergoing CABG.9
Our findings are consistent with previous studies suggesting protective benefit of statins in surgical patients, and suggest that statins may proffer benefit to patients through the reduction of their risk for developing clinically significant POAF. There is a biologic basis to support the idea that statins may have a direct anti-arrhythmic effect,10,24,25
and our data provides supporting evidence for this mechanism. It is, however, also possible that our data are describing an indirect association between statin use, other complications of surgery, and POAF. For instance, there is current controversy as to whether statin use decreases post-operative sepsis,26–28
an effect that could cause a decrease in POAF as a downstream consequence. It is difficult to tease apart such indirect associations in these data. However, the fact that statins do not appear to be associated with any differences in subsequent outcomes among patients who develop POAF suggests that statins’ anti-arrhythmic effects are an important part of their protective profile.
It is important to point out that statin use, as defined in this paper, likely represents longitudinal use of the medication. Unlike beta-blockers, statins are infrequently started at the time of surgery or acutely during hospitalization. Therefore, the data presented likely represent longer-term use of these medications, with the attendant likelihood that other elements of the patient’s care may have been managed over the longer term as well. To address this potential bias, secondary analyses were performed using propensity score methods to account for socioeconomic or clinical factors associated with statin administration; these results were essentially identical to the findings from the standard fully adjusted regression model.
Our study has a number of limitations. We did not have the ability to track what medications patients were taking prior to hospitalization, thus preventing us from identifying which patients had statin withdrawal, longitudinal continuation of statin, or new prescription of statin. This limited our ability to assess the acute efficacy of statin therapy and the effect of statin withdrawal, which is thought to be a risk factor for cardiovascular events. 20,29
Since administrative data was used, subtle clinical information, such as the incidence of delirium, surgical site infection, or other potential contributing causes of POAF is lacking. Echocardiographic parameters which may have represented important confounding variables, such as left atrial size, were not available within the database. The timing and duration of POAF episodes were also unavailable for review -- such information could have provided further insight as to the clinical significance of each arrhythmic event. In addition, the data do not include detailed past medical history information. For that reason, the present-on-admission coding was employed to discern incident from prevalent atrial fibrillation and standard risk adjustment methodologies were used to account for patient risk factors. The use of present-on-admission codes does not, however, allow us to draw the important distinction between sub-types of pre-existing atrial fibrillation: paroxysmal, persistent, and long-standing persistent. Though the use of these codes is becoming more common, many of the pitfalls involved with their use are related to potentially variable coding practices between hospitals.30,31
To address this problem, we used data only from sites which were 100% compliant with present-on-admission coding, and limited our outcome variable to groups most likely to have had clinically significant atrial fibrillation. Moreover, sensitivity analyses showed that statin medications retained their protective effect when patients with pre-existing atrial fibrillation were excluded from the cohort. Additionally, we acknowledge that patients treated with lipid-lowering medications could have been healthier than those that were statin untreated, or that the administration of a statin may have simply been a marker for higher quality operative and peri-operative care. Reassuringly, however, our results were consistent across subgroups and in the marginal effects regression model.