Does Statin Use Prevent Recurrent Stroke in Ischemic Stroke Patients with Atrial Fibrillation?

Despite the inconsistent or weak association between cholesterol and stroke, a decrease in cholesterol levels with statins can reduce the incidence of stroke in high-risk populations and in patients with a stroke or transient ischemic attack. Most mechanisms for statin therapy to prevent future stroke was due to lowering atherothrombosis and the only large recurrent stroke prevention trial, SPARCL, excluded stroke patients with atrial fibrillation. Therefore it is difficult to know whether statin therapy reduces risks of cardioembolic stroke. Some ischemic stroke patients have both atrial fibrillation and atherosclerosis and it may be difficult to clarify a real mechanism responsible for the stroke. Among ischemic stroke patients from Taiwan Stroke Registry, 16.5% had atrial fibrillation and 49.4% had dyslipidemia and it is conceivable that some ischemic stroke patients are likely to have both atrial fibrillation and hypercholesteremia. Also, a study showed that atrial fibrillation upregulates CD40 expression and platelet adhesion to the endocardium and simvastatin is effective in modulating this expression, thus it may potentially contribute to reduce the risk of intra-atrial thrombus formation. Furthermore, a randomized controlled trial enrolling 34 elderly patients with atrial fibrillation showed that intensive cholesterol lowering with atorvastatin significantly reduced inflammation and was accompanied by reduced thrombin generation. Based on these findings, it may be reasonable to hypothesize that statin therapy may reduce stroke risk in patients with atrial fibrillation through reducing thrombus formation. The objective of this study is to clarify whether statin therapy can reduce risk of recurrent stroke in ischemic stroke patients with atrial fibrillation. The Taiwan National Health Insurance Research Database (NHIRD) is a longitudinal data, which contains complete outpatient clinic visits, hospitalization and prescription for 99% of population in Taiwan. We will use NHIRD as data source and conduct a retrospective cohort study. Our source population comprised all beneficiaries aged≧18 years with continuous cover age from January 1, 1997 to December 31, 2011 who were hospitalized due to ischemic stroke. The exposed group is people received statin during the follow-up period and non-exposed group is people who did not receive statin. All subjects will have at least one year follow-up. The population will be followed from index stroke to the date of recurrent stroke, death, or the last medical claim, whichever comes first. The primary endpoint is recurrent stroke. The secondary endpoints are hemorrhage stroke, ischemic stroke, myocardial infarction, new-onset diabetes mellitus, and all-cause mortality. We will use Cox’s proportional hazards model to estimate the crude and adjusted hazard ratio and 95% confidence intervals, which considered non-exposed group as reference group.

Project ID:PC10207-0369
External Project ID:NSC102-2628-B182-012