What is the clinical evidence from this study?

Study design: Cohort. Population: COVID-19 and Ischaemic Heart Disease (n=30056). Intervention: ACEI/ARB vs. No ACEI/ARB treatment. Primary outcome: All-cause mortality (Adjusted OR 0.26, 95% CI 0.08-0.92, p=0.037).

November 10, 2025BMC Infectious Diseases1 citationsOpen Access

Impact of ACEI/ARB use on COVID-19 mortality in patients with ischaemic heart disease: insights from South Korean National health insurance service data

Q: What does this research mean for the field?

ACEI/ARB treatment is associated with a 74% lower odds of mortality compared to non-treatment in COVID-19 patients with ischaemic heart disease. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

SKShin‐Woo KimHankuk University of Foreign Studies TGTaewan GooSeoul National University SNSeunghwan NohNortheastern University

Key Result

ACEI/ARB treatment was associated with a 74% lower odds of mortality compared to non-treatment in COVID-19 patients with ischaemic heart disease.

Study Design

Type

Cohort (n=30,056)

Multicenter

Yes

Structured PICO

Does ACEI/ARB use reduce all-cause mortality in COVID-19 patients with ischaemic heart disease?

Population

30,056 adults (age ≥ 18 years) with confirmed COVID-19 (ICD-10: U07.1) and continuous NHIS enrollment ≥ 12 months, stratified by ischaemic heart disease (IHD) status, from the South Korean National Health Insurance Service (NHIS) database.

Intervention

Angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) use, defined as prescription records for ≥ 30 consecutive days within 90 days preceding COVID-19 diagnosis.

Comparator

No ACEI/ARB use (no prescription records meeting the ≥ 30 consecutive days criteria within 90 days preceding COVID-19 diagnosis).

Outcome

All-cause mortality from COVID-19 diagnosis until death or December 31, 2020 (median follow-up 180 days).hard clinical

In a large South Korean cohort, ACEI/ARB use was associated with a significant 74% reduction in the odds of all-cause mortality among COVID-19 patients with underlying ischaemic heart disease, an effect that was particularly pronounced in patients over 70 years of age.

Main Result

Effect estimate: Adjusted OR 0.26 (95% CI 0.08-0.92)

Absolute Event Rate: 14.8% vs 24.1%

p-value: p=0.037

Limitations

Observational study design cannot establish causal relationships
IHD definition omitted procedure codes, potentially leading to under-detection
90-day medication exposure window may not capture all treatment patterns
Lack of time-to-event (Cox proportional hazards) analysis
Database lacks detailed medication dosage and adherence information
Inability to distinguish COVID-19-specific deaths from other causes
Unmeasured confounders such as BMI and smoking status
Lack of composite comorbidity scores for risk adjustment
Limited generalizability due to the Korean-specific cohort

Abstract

BACKGROUND: The COVID-19 pandemic has highlighted the importance of understanding the complex interactions between pre-existing conditions, such as ischaemic heart disease (IHD), and mortality risk. This study aims to investigate the associations among COVID-19 mortality, the presence of IHD, and the use of angiotensin receptor blockers (ARBs) and angiotensin-converting-enzyme inhibitors (ACEIs) by leveraging the South Korean National Health Insurance Service (NHIS) big data. METHODS: We conducted a retrospective cohort study of 30,056 patients with COVID-19 from the NHIS. The study population was stratified into four groups based on IHD status and the use of ACEI/ARBs. To assess their effects on mortality, we applied inverse probability of treatment weighting (IPTW) to balance baseline covariates, followed by a weighted logistic regression. The interaction between IHD and ACEI/ARB use was evaluated on both multiplicative (interaction term) and additive scales (Relative Excess Risk Due to Interaction, RERI), supplemented by an age-stratified analysis (≤ 70 vs. >70 years). RESULTS: Among 30,056 COVID-19 patients, we identified a significant interaction between IHD and ACEI/ARB use on mortality after adjusting for confounders. The main finding revealed that among patients with IHD, ACEI/ARB treatment was associated with 74% lower odds of mortality compared to non-treatment (Adjusted OR: 0.26, 95% CI: 0.08-0.92, p = 0.037). This protective interaction was strongly age-dependent, remaining statistically significant only in patients older than 70 (Interaction OR: 0.53, 95% CI: 0.27-0.99; p = 0.048). Furthermore, a significant antagonistic interaction on the additive scale (RERI: - 1.77, 95% CI - 3.04 to - 0.51; p = 0.006) confirmed a combined protective effect greater than the sum of the individual effects. CONCLUSIONS: This study leverages the NHIS big data to provide a comprehensive analysis of the complex interactions among IHD, ACEI/ARB use, demographic factors, and comorbidities in the context of COVID-19 mortality. Our findings suggest a 45% reduction in the odds of mortality for IHD patients taking ACEI/ARB, particularly those over 70 years, but randomised controlled trials are needed before clinical guideline changes. The findings highlight the protective effect of ACEI/ARB in patients with IHD and emphasize the importance of personalized treatment approaches considering patient characteristics, pre-existing conditions, and medication use.

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