Statin therapy and synergistic effect of ezetimibe for the prevention of stroke with atrial fibrillation populations: nationwide cohort study
C H Kim, K H Lee, Y H LeeAbstract
Objective
Statins are widely recommended for the prevention of atherosclerotic cardiovascular disease (ASCVD), and ezetimibe has emerged as a complementary lipid lowering agent, potentially reducing statin-related side effects. However, the efficacy of statins and ezetimibe in preventing ischemic stroke among patients with atrial fibrillation (AF) is still controversial.
Purpose
We aimed to evaluate the effect of statin and ezetimibe therapy on the risk reduction of stroke in patients with AF using a large population-based cohort.
Materials and Methods
From the Korean National Health Insurance Service database, between Jan 2012 to Dec 2020, 592,220 patients with sufficient clinical data were included. The primary endpoint was the 3-year incidence of net adverse clinical and cerebral events (NACCE), defined as a composite of all-cause death, stroke, acute coronary syndrome, or major bleeding. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using multivariable Cox regression models, and to reduce confounding, propensity score matching and inverse probability weighting was applied.
Results
Compared with no statin therapy, statin use without ezetimibe significantly reduced the risk of NACCE (HR 0.891, 95% CI, 0.878-0.903; p-value < 0.001), and combination therapy with ezetimibe was associated with a further reduction in risk (HR 0.811, 95% CI, 0.796-0.827; p-value < 0.001). A dose-response relationship was observed, with higher statin intensity with lower NACCE rates (moderate-intensity HR 0.924, 95% CI, 0.862-0.99; p-value = 0.025; high-intensity HR 0.88, 95% CI, 0.783-0.989; p-value 0.031) than low-intensity statin therapy. Notably, combination therapy with low- to moderate-intensity statin plus ezetimibe (HR 0.741, 95% CI, 0.594-0.925; p-value = 0.008) achieved a comparable risk reduction with that of high intensity statin (Wald p-value = 0.332). High intensity statin therapy was significantly associated with new-onset diabetes mellitus (NODM) (HR 1.243, 95% CI, 1.025-1.507; p-value = 0.027) in contrast to no risk increment with low-to moderate intensity statin.
Conclusion
In patients with AF, statin therapy, particularly when combined with ezetimibe, significantly reduces the risk of death, stroke, and other major adverse events. Low- to moderate-intensity statin plus ezetimibe therapy provides efficacy comparable to high-intensity statin therapy without NODM risk increment.