Class-Specific Effects of ARBs Versus ACE Inhibitors on Survival and Cardiovascular Outcomes in MASLD

Q: What are the key findings of this study?

ARB use was associated with lower all-cause mortality and cardiovascular events compared to ACEI use in patients with MASLD.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Metabolic dysfunction-associated steatotic liver disease (MASLD) (n=52143). Intervention: Angiotensin II receptor blockers (ARBs) vs. Angiotensin-converting enzyme inhibitors (ACEIs). Primary outcome: All-cause mortality in the MASLD subgroup (IPTW-adjusted) (HR 0.94, 95% CI 0.90-1.00, p=0.031).

Q: What does this research mean for the field?

In patients with metabolic dysfunction-associated steatotic liver disease (MASLD), ARB use is associated with significantly lower all-cause mortality and reduced cardiovascular event risk compared to ACE inhibitor use. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Tom Ryu; Yeon Seo; Jaejun Lee; Ji Won Han; Hyun Yang; Keungmo Yang

doi:10.3390/ijms262010061

October 16, 2025International Journal of Molecular SciencesOpen Access

Class-Specific Effects of ARBs Versus ACE Inhibitors on Survival and Cardiovascular Outcomes in MASLD

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Key result

ARB use is linked to ~6% lower all-cause mortality vs. ACEIs in MASLD.

HR 0.94
95% CI 0.90-1.00
P=0.031
n=52,143

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Why the study?

RAS inhibitors improve outcomes in MASLD, but the differential impact of ACE inhibitors versus ARBs on survival and cardiovascular outcomes was unknown.

Does angiotensin II receptor blocker (ARB) use compared to angiotensin-converting enzyme inhibitor (ACEI) use reduce all-cause mortality and cardiovascular events in adults with metabolic dysfunction-associated steatotic liver disease (MASLD)?

Key Points

To evaluate the differential effects of angiotensin II receptor blockers versus angiotensin-converting enzyme inhibitors on all-cause mortality and cardiovascular outcomes in individuals with metabolic dysfunction-associated steatotic liver disease.
Population-based cohort study using UK Biobank data of 52,143 participants exclusively taking an ACEI (n=36,730) or ARB (n=15,413), followed for a median of 14.8 years.
MASLD was defined by a fatty liver index ≥ 60 plus ≥1 cardiometabolic risk factor; inverse probability of treatment weighting (IPTW) was applied to adjust for baseline confounders.
Among individuals with MASLD, ARB use was associated with significantly lower all-cause mortality compared to ACEI use (1.170 vs 1.248 deaths per 100 person-years; IPTW-adjusted HR, 0.94; 95% CI, 0.90–1.00; p = 0.031).
Cardiovascular risk was significantly lower with ARBs compared to ACEIs in MASLD (HR, 0.92; 95% CI, 0.89–0.96; p < 0.001), with pronounced benefits in individuals with BMI ≥ 25 kg/m2 and without diabetes.
No significant differences were observed between drug classes regarding hepatic decompensation or hepatocellular carcinoma, and survival benefits were not observed in individuals without steatotic liver disease.

Study Design

Type

Cohort (n=52,143)

Multicenter

Yes

Structured PICO

Does angiotensin II receptor blocker (ARB) use compared to angiotensin-converting enzyme inhibitor (ACEI) use reduce all-cause mortality and cardiovascular events in adults with metabolic dysfunction-associated steatotic liver disease (MASLD)?

P

Population

52,143 UK Biobank participants aged 40-69 years with exclusive use of either an ARB (n=15,413) or ACEI (n=36,730), evaluated by MASLD status (FLI >=60 plus >=1 cardiometabolic risk factor, free of other chronic liver diseases) over a median follow-up of 14.8 years.

E

Exposure

Exclusive baseline use of angiotensin II receptor blockers (ARBs: losartan, valsartan, irbesartan, candesartan cilexetil, telmisartan, eprosartan, olmesartan) over a median follow-up of 14.8 years.

C

Comparator

Exclusive baseline use of angiotensin-converting enzyme inhibitors (ACEIs: lisinopril, enalapril, ramipril, captopril, quinapril, perindopril) over a median follow-up of 14.8 years.

O

Outcome

All-cause mortality and cardiovascular events (identified via linkage with national Hospital Episode Statistics and death registries) over a median follow-up of 14.8 years (IQR 13.9-15.6) after inverse probability of treatment weighting (IPTW).hard clinical

Main Result

Hazard Ratio: 0.94 (95% CI 0.9–1)

Absolute Event Rate: 1.17% vs 1.248%

p-value: p=0.031

In a large UK Biobank cohort of patients with MASLD, ARBs were associated with lower all-cause mortality and fewer cardiovascular events than ACEIs, supporting potential preferential use of ARBs when RAS inhibition is indicated in patients with steatotic liver disease.

Limitations

Medication exposure was based on self-report at baseline without data on dose, adherence, or longitudinal treatment changes, precluding a new-user or time-varying design.
Observational design with potential for residual and unmeasured confounding (e.g., ACEIs potentially prescribed more often to higher cardiovascular risk patients such as those with heart failure or post-MI).
Inability to exclude differential effects within specific drug subclasses of ARBs or ACEIs.
Fibrosis severity and hepatic steatosis were assessed using surrogate noninvasive biomarkers (FLI, FIB-4, NFS) rather than liver histology.
Spatial transcriptomic analyses were exploratory, derived from mouse liver models, and warrant caution when extrapolating across species.
Medication exposure was self-reported at baseline without information on dose, adherence, or longitudinal changes, precluding a new-user or time-varying design and potentially introducing immortal-time bias.
Potential for unmeasured and residual confounding despite IPTW adjustment (e.g., channeling bias where ACEIs are prescribed more frequently for heart failure or post-myocardial infarction).
Agents were grouped by drug class, precluding evaluation of intra-class differences among individual ARBs or ACEIs.
Steatosis and liver fibrosis were evaluated using noninvasive surrogate indices (FLI, FIB-4, NFS) rather than liver biopsy histology.
Mouse spatial transcriptomic analyses from the Liver Cell Atlas were exploratory and not directly linked to causal inference in humans.

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Implication

May support ARB preference over ACEI in MASLD when RAS inhibition is indicated; leaves open confirmation in randomized trials.

Abstract

Renin–angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), have been associated with improved outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to assess the differential impact of ACEIs versus ARBs on survival and cardiovascular outcomes in individuals with MASLD. Using data from the UK Biobank, we identified 52,143 participants with exclusive use of either an ACEI or ARB. Individuals with viral, autoimmune, cholestatic, or alcohol-related liver disease were excluded. MASLD was defined as fatty liver index ≥ 60 with ≥1 cardiometabolic risk factor. Inverse probability of treatment weighting (IPTW) was used to adjust for confounders. Outcomes included all-cause mortality, cardiovascular events, hepatic decompensation, and hepatocellular carcinoma (HCC), analyzed using Cox proportional hazards models. Among MASLD participants, ARB use was associated with significantly lower all-cause mortality compared to ACEI use (HR, 0.94; 95% CI, 0.90–1.00; p = 0.031) after IPTW adjustment. Cardiovascular risk was also lower with ARBs (HR, 0.92; 95% CI, 0.89–0.96; p < 0.001), particularly in subgroups with BMI ≥ 25 kg/m2, no diabetes, and advanced fibrosis. No differences in hepatic decompensation or HCC incidence were observed. Benefits of ARBs were not significant in participants without steatotic liver disease. ARB use was associated with improved survival and reduced cardiovascular events in individuals with MASLD, whereas ACEIs expressed no comparable benefit. These findings suggest that ARBs might be a more effective RAS inhibitor subclass in MASLD and support their preferential use in patients with steatotic liver disease requiring antihypertensive therapy.

Discussion

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Cite This Study

Ryu et al. (2025) conducted a cohort in Metabolic dysfunction-associated steatotic liver disease (MASLD) (n=52,143). Angiotensin II receptor blockers (ARBs) vs. Angiotensin-converting enzyme inhibitors (ACEIs) was evaluated on All-cause mortality in the MASLD subgroup (IPTW-adjusted) (HR 0.94, 95% CI 0.90-1.00, p=0.031). ARB use was associated with lower all-cause mortality and cardiovascular events compared to ACEI use in patients with MASLD.

synapsesocial.com/papers/6aa119b6f68c3a7f111a10d1 https://doi.org/10.3390/ijms262010061

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Class-Specific Effects of ARBs Versus ACE Inhibitors on Survival and Cardiovascular Outcomes in MASLD

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Class-Specific Effects of ARBs Versus ACE Inhibitors on Survival and Cardiovascular Outcomes in MASLD

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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