Silent lacunar infarction and risk of cerebrovascular events in patients treated with direct-acting oral anticoagulants

Background Silent lacunar infarction (LACI) is a common subtype of silent brain infarction, frequently detected incidentally on neuroimaging, especially in elderly individuals. Despite its high prevalence, the clinical outcomes and optimal management strategies for patients with silent LACI receiving direct-acting oral anticoagulants (DOACs) remain unclear and have been overlooked by cardiologists. Purpose Under the condition of DOACs treatment, to investigate the clinical outcomes and risk management of silent LACI patients. Methods In this multi-center cohort based on electronic health records, we used a new-user design to identify 36,994 adults (mean age 68 years, 49.8% female) who initiated DOAC therapy between January 2015 and June 2020. Patients with symptomatic cerebrovascular disease were excluded. We applied multivariable-adjusted Cox models to estimate associations between silent LACI and adverse outcomes, including ischemic stroke (IS), intracranial hemorrhage (ICH), and all-cause mortality. Results 1,018 IS, 241 ICH, and 2,747 deaths were recorded over a maximum follow-up of three years. Compared with those without LACI, silent LACI was associated with higher risks of IS (hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.40-2.04), ICH (HR: 1.56; 95% CI: 1.03-2.38), and mortality (HR: 1.22; 95% CI: 1.08-1.38). Multiple risk control interventions, particularly antihypertensive therapy, were linked to reduced mortality among LACI patients (P for interaction = 0.016). Conclusion Silent LACI confers elevated risks of cerebrovascular events and mortality in patients on DOAC therapy. These findings highlight the need for vigilant monitoring and personalized risk-factor management to optimize outcomes in this high-risk population. Further research is warranted to investigate pathophysiological mechanisms and refine targeted treatment strategies, particularly focusing on balancing ischemic and hemorrhagic risks in clinical practice and future trials.