Lipid control and stroke risk in atrial fibrillation patients treated with direct oral anticoagulants and statins

INTRODUCTION: The risk of ischemic stroke and intracerebral hemorrhage (ICH) with intensive lipid control by statins among patients with atrial fibrillation (AF) who require direct oral anticoagulants (DOAC) is unclear. We aimed to determine the risks of ischemic stroke and ICH in AF patients treated with DOAC and statins. PATIENTS AND METHODS: In a population-based retrospective cohort study, we identified AF patients concurrently on DOAC and statins from 2015 to 2021 in Hong Kong. Primary outcome was ischemic stroke. Secondary outcomes were ICH and death. We correlated study outcomes with low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) as time-varying, continuous variables with restricted cubic spline. In secondary analyses, the risks of study outcomes with statin intensity (low, moderate, high) were determined by multivariable time-dependent marginal structural Cox models. RESULTS: We identified 32,752 AF patients co-prescribed with DOAC and statins. Lower LDL-C (p < 0.001) and higher HDL-C (p < 0.001) levels were associated with lower risk of ischemic stroke but not significantly associated with ICH. LDL-C of <1.8 mmol/L (70 mg/dL) was not associated with mortality (19.6% vs 18.4%, difference 1.2% [95% CI -0.35 to 2.13]). High-intensity statin was associated with a lower risk of ischemic stroke compared with low-intensity statin (weighted Cox-specific hazard ratio [95% CI]: 0.82 [0.67-0.99], p = 0.040) independent of LDL-C levels. Similar associations were found in 11,444 AF patients with a history of ischemic stroke. DISCUSSION AND CONCLUSION: Intensive lipid control by high-intensity statins was associated with a lower risk of ischemic stroke in AF patients who required DOACs and did not appear to increase the risk of ICH.