Abstract: Objective To investigate the association between renin-angiotensin system inhibitor(RASi) use and the risk of all-cause mortality among patients with steatotic liver disease(SLD) and hypertension. Methods Using an emulated target clinical trial design, that included new users of either RASi or calcium channel blocker(CCB) for at least 60 days among patients with SLD and hypertension who participated in chronic disease manage- ment in the Kailuan cohort from 2006 to 2020. Baseline characteristic differences between the groups were balanced by multivariable adjustment and propensity score(PS) matching. Cox proportional hazards regression models were used to evaluate the association between RASi use and all-cause mortality risk. Furthermore, the landmark analysis was applied to explore the dose-response relationship between the cumulative duration of RASi use and all-cause mortality risk. Results A total of 2 085 patients with SLD and hypertension were included. During a median follow-up of 7.01 years, 510 patients died. The mortality rate was lower in the RASi group than that in the CCB group(8-year mortality: 19.53% vs. 22.78%, P＜0.01). After multivariable adjustment for baseline factors, the risk of all-cause mortality in the RASi group was reduced by 28% when compared to that in the CCB group(HR=0.72, 95% CI: 0.60-0.87). Stratified analyses found no heterogeneity in the negative association between RASi use and all-cause mortality risk across the subgroups. The results were consistent in the PS-matched population(HR=0.77, 95% CI: 0.62-0.96). Dose-response analysis indicated a decreasing trend in all-cause mortality risk with increasing cumulative duration of RASi use(P for trend ＜0.05). Conclusions RASi use is associated with a reduced risk of all-cause mortality among patients with SLD and hypertension, and this benefit increases with longer cumulative duration of RASi use. These results provide strong evidence to guide medication selection and to long-term management in this population.

Key words: steatotic liver disease, hypertension, emulated target clinical trial, renin-angiotensin system inhibitor, all-cause mortality