Epidemiology and Health

Original Articles

Safety of combination therapy of azilsartan medoxomil and amlodipine: a population-based cohort study: Hyesung Lee, Bin Hong, Chris Tzu-Ting Su, Sungho Bea, Han Eol Jeong, Kyungyeon Jung, Michael Chun-Yuan Cheng, Zoe Chi-Jui Chang, Edward Chia-Cheng Lai, Jongyoung Lee; Epidemiol Health. 2025;47:e2025029. Published online May 28, 2025; DOI: https://doi.org/10.4178/epih.e2025029

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Abstract Summary PDF Supplementary Material

Abstract

OBJECTIVES
This study investigated the safety of azilsartan and amlodipine combination therapy versus other angiotensin receptor blockers (ARBs) and amlodipine in patients with hypertension.

METHODS

We conducted a cohort study utilizing healthcare databases from Korea and Taiwan. Patients aged between 18 years and 75 years who were newly prescribed both an ARB and amlodipine within 6 months of hypertension diagnosis were included. Safety outcomes assessed were hypotension, angioedema, acute pancreatitis, hyperkalemia, hypokalemia, toxic liver disease, hepatic failure, nausea and vomiting, and fall-related injury. Hazard ratios (HRs) with 95% confidence intervals (CIs) for each safety outcome associated with azilsartan medoxomil and amlodipine versus other ARBs combined with amlodipine were calculated within a 1:1 propensity score (PS)-matched cohort. Summary HRs across databases were computed using random-effects meta-analysis.

RESULTS

We identified 2,472 eligible patients (1,521 from Korea, 951 from Taiwan) initiating treatment with azilsartan medoxomil and amlodipine, and 671,468 patients (312,322 from Korea, 355,409 from Taiwan) initiating other ARBs with amlodipine. After PS matching, baseline characteristics were well-balanced between treatment groups. During the 180-day follow-up, most adverse outcomes did not occur even once in either group, thus precluding the calculation of HRs. The risk of acute pancreatitis was not significantly different between the azilsartan medoxomil and amlodipine group and the other ARB and amlodipine groups (summary HR, 0.86; 95% CI, 0.14 to 5.37).

CONCLUSIONS

In this population-based cohort study, azilsartan medoxomil combined with amlodipine was not associated with an increased risk of adverse outcomes compared to other ARBs combined with amlodipine.

Summary

Korean summary
Azilsartan medoxomil과 amlodipine 병용요법의 장기적인 안전성을 평가한 연구는 제한적임. 본 코호트 연구에서는 azilsartan과 amlodipine 병용요법이 다른 ARB-amlodipine 병용요법에 비해 중대한 이상반응 발생 위험을 증가시키지 않는 것으로 나타났음. 이러한 결과는 고혈압 환자에서 azilsartan-amlodipine 병용요법의 실제 진료 환경에서의 안전성을 뒷받침함.

Key Message
Limited studies have evaluated the long-term safety of combined azilsartan medoxomil and amlodipine therapy. This cohort study found the azilsartan and amlodipine combination therapy was not associated with increased risk of serious adverse events compared to other ARB-amlodipine combinations. These results support the real-world safety of azilsartan-amlodipine caombination therapy in patients with hypertension.

Citations

Citations to this article as recorded by

Letter to the Editor: Safety of combination therapy of azilsartan medoxomil and amlodipine: a population-based cohort study
Zhanyi Zhou
Epidemiology and Health.2025; 47: e2025053. CrossRef
Authors’ Reply: Safety of combination therapy of azilsartan medoxomil and amlodipine: a population-based cohort study
Hyesung Lee, Bin Hong, Chris Tzu-Ting Su, Sungho Bea, Han Eol Jeong, Kyungyeon Jung, Michael Chun-Yuan Cheng, Zoe Chi-Jui Chang, Edward Chia-Cheng Lai, Jongyoung Lee
Epidemiology and Health.2025; 47: e2025054. CrossRef

A comparison of methods for the measurement of adherence to antihypertensive multidrug therapy and the clinical consequences: a retrospective cohort study using the Korean nationwide claims database: Minji Jung, Eunjung Choo, Sukhyang Lee; Epidemiol Health. 2023;45:e2023050. Published online May 1, 2023; DOI: https://doi.org/10.4178/epih.e2023050

16,449 View
154 Download
2 Web of Science
2 Crossref

Abstract Summary PDF Supplementary Material

Abstract

OBJECTIVES
In observational studies, the methods used to measure medication adherence may affect assessments of the clinical outcomes of drug therapy. This study estimated medication adherence to multidrug therapy in patients with hypertension using different measurement methods and compared their impacts on clinical outcomes.

METHODS

This was a retrospective cohort study using the Korean National Health Insurance Service–National Sample Cohort database (2006-2015). Adults diagnosed with hypertension who initiated multidrug antihypertensive therapy in the index year 2007 were included. Adherence was defined as over 80% compliance. Adherence to multidrug antihypertensive therapy was measured in 3 ways using the proportion of days covered (PDC) with 2 approaches to the end-date of the study observations: PDC with at least one drug (PDC<sub>with≥1</sub>), PDC with a duration weighted mean (PDC<sub>wm</sub>), and the daily polypharmacy possession ratio (DPPR). The primary clinical outcome was a composite of cardiovascular and cerebrovascular disease-specific hospitalizations or all-cause mortality.

RESULTS

In total, 4,226 patients who initiated multidrug therapy for hypertension were identified. The mean adherence according to the predefined measurements varied from 72.7% to 79.8%. Non-adherence was associated with an increased risk of a primary outcome. The hazard ratios (95% confidence intervals, CIs) primary outcomes varied from 1.38 (95% CI, 1.19 to 1.59) to 1.44 (95% CI, 1.25 to 1.67).

CONCLUSIONS

Non-adherence to multidrug antihypertensive therapy was significantly associated with an increased risk of a primary clinical outcome. Across the varying estimates based on different methods, medication adherence levels were similar. These findings may provide evidence to support decision-making when assessing medication adherence.

Summary

Korean summary
- 여섯 가지 다중약물 순응도 평가 방법을 적용했을 때, 고혈압제 병용 요법 순응도는 70~80%으로 유사한 결과값을 보였다. - 순응군 대비 비순응군에서 심혈관질환 관련 입원 및 전체 사망 위험 증가가 1.4배 높았다.

Key Message
-In Korea, adherence to multidrug antihypertensive therapy was approximately 70~80% across the six measurements. -Similar impacts of adherence to multidrug antihypertensive therapy upon the clinical consequences with a 4-folds increased risk across the six measurements. -We provide evidence for decision-making of applying adherence measurement in observational analysis.

Citations

Citations to this article as recorded by

The link between adherence to antihypertensive medications and mortality rates in patients with hypertension: a systematic review and meta-analysis of cohort studies
Xuemei Peng, Lihong Wan, Benkai Yu, Jianhui Zhang
BMC Cardiovascular Disorders.2025;[Epub] CrossRef
Calcium Channel Blocker Versus Renin–Angiotensin System Inhibitor in Risk of Kidney Cancer Among Patients With Hypertension: A Propensity Score‐Matched Cohort Study
Minji Jung, Shufeng Li, Zhengyi Deng, Jinhui Li, Mingyi Li, Satvir Basran, Marvin E. Langston, Benjamin I. Chung
Cancer Medicine.2024;[Epub] CrossRef

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