Impact of ACEI/ARB use on COVID-19 mortality in patients with ischaemic heart disease: insights from South Korean National health insurance service data
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...
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| Published in: | BMC infectious diseases Vol. 25; no. 1; pp. 1529 - 12 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
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BioMed Central
10.11.2025
BioMed Central Ltd BMC |
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| ISSN: | 1471-2334, 1471-2334 |
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| 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. |
|---|---|
| AbstractList | 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.
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).
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.
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. 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. 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. 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 ([less than or equal to] 70 vs. >70 years). 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. 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. 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.BACKGROUNDThe 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.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).METHODSWe 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).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.RESULTSAmong 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.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.CONCLUSIONSThis 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. 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 ([less than or equal to] 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. Keywords: COVID-19 mortality, Ischaemic heart disease, Angiotensin receptor blockers, Angiotensin-Converting enzyme inhibitors, National health insurance data 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. |
| ArticleNumber | 1529 |
| Audience | Academic |
| Author | Kim, Shin-Woo Noh, Seunghwan Oh, Bumjo Goo, Taewan Lee, Seungyeoun Park, Taesung |
| Author_xml | – sequence: 1 givenname: Shin-Woo surname: Kim fullname: Kim, Shin-Woo organization: Department of Internal Medicine, School of Medicine, Kyungpook National University – sequence: 2 givenname: Taewan surname: Goo fullname: Goo, Taewan organization: Interdisciplinary Program in Bioinformatics, Seoul National University – sequence: 3 givenname: Seunghwan surname: Noh fullname: Noh, Seunghwan organization: Department of Economics, College of Social Sciences, Seoul National University – sequence: 4 givenname: Seungyeoun surname: Lee fullname: Lee, Seungyeoun organization: Department of Mathematics & Statistics, Sejong University – sequence: 5 givenname: Bumjo surname: Oh fullname: Oh, Bumjo organization: Department of Family Medicine, Seoul National University College of Medicine, Department of Family Medicine, SMG-SNU Boramae Medical Center – sequence: 6 givenname: Taesung surname: Park fullname: Park, Taesung email: tspark@stats.snu.ac.kr organization: Department of Statistics, Seoul National University |
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The COVID-19 pandemic has highlighted the importance of understanding the complex interactions between pre-existing conditions, such as ischaemic... The COVID-19 pandemic has highlighted the importance of understanding the complex interactions between pre-existing conditions, such as ischaemic heart disease... Background The COVID-19 pandemic has highlighted the importance of understanding the complex interactions between pre-existing conditions, such as ischaemic... Abstract Background The COVID-19 pandemic has highlighted the importance of understanding the complex interactions between pre-existing conditions, such as... |
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| SubjectTerms | Adult Aged Aged, 80 and over Angiotensin II receptor blockers Angiotensin Receptor Antagonists - therapeutic use Angiotensin receptor blockers Angiotensin-Converting enzyme inhibitors Angiotensin-Converting Enzyme Inhibitors - therapeutic use Cardiac patients Care and treatment Comorbidity COVID-19 - complications COVID-19 - mortality Diagnosis Dosage and administration Enzyme inhibitors Female Humans Infectious Diseases Internal Medicine Ischaemic heart disease Male Medical Microbiology Medicine Medicine & Public Health Middle Aged Myocardial Ischemia - complications Myocardial Ischemia - drug therapy Myocardial Ischemia - epidemiology Myocardial Ischemia - mortality National health insurance data National Health Programs Parasitology Republic of Korea - epidemiology Retrospective Studies SARS-CoV-2 Tropical Medicine |
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| Title | Impact of ACEI/ARB use on COVID-19 mortality in patients with ischaemic heart disease: insights from South Korean National health insurance service data |
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