Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension

Anuradhaa Subramanian; Diana Han; Tasanee Braithwaite; Rasiah Thayakaran; Dawit T Zemedikun; Krishna M Gokhale; Wen Hwa Lee; Jesse Coker; Pearse A Keane; Alastair K Denniston; Krishnarajah Nirantharakumar; Laurent Azoulay; Nicola J Adderley

doi:10.1111/bcp.15366

Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension

Anuradhaa Subramanian, Diana Han, Tasanee Braithwaite, Rasiah Thayakaran, Dawit T Zemedikun, Krishna M Gokhale, Wen Hwa Lee, Jesse Coker, Pearse A Keane, Alastair K Denniston, Krishnarajah Nirantharakumar^*, Laurent Azoulay, Nicola J Adderley

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Aims: Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK. Methods: In this study, 53 832 and 43 106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD. Results: During a median follow-up of 2 years (interquartile range 1–5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2–2.6) and 2.2 (2.0–2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90–1.27] and 0.87 [0.71–1.07], respectively). Conclusion: We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.

Original language	English
Pages (from-to)	4199-4210
Number of pages	12
Journal	British Journal of Clinical Pharmacology
Volume	88
Issue number	9
Early online date	27 Apr 2022
DOIs	https://doi.org/10.1111/bcp.15366
Publication status	Published - Sept 2022

Bibliographical note

Funding Information:
Drs Adderley, Nirantharakumar and Denniston reported a grant from Action Against Age‐related Macular Degeneration during the conduct of the study. Dr Adderley reported receiving grants from Medical Research Council, National Institute for Health Research and National Institute for Health Research RfPB outside the submitted work. Dr Nirantharakumar reported receiving grants from Medical Research Council, National Institute for Health Research, AstraZeneca, MSD, Boehringer Ingelheim, Vifor, and Health Data Research UK and personal fees from Sanofi outside the submitted work. Dr Denniston reported receiving grant support from Health Data Research UK outside the submitted work. Dr Braithwaite reported receiving salary support from the patient charity Olivia's Vision. No other disclosures were reported.

Publisher Copyright:
© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Keywords

Angiotensin-converting enzyme inhibitors
age-related macular degeneration
hypertension

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Subramanian, A., Han, D., Braithwaite, T., Thayakaran, R., Zemedikun, D. T., Gokhale, K. M., Lee, W. H., Coker, J., Keane, P. A., Denniston, A. K., Nirantharakumar, K., Azoulay, L., & Adderley, N. J. (2022). Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension. British Journal of Clinical Pharmacology, 88(9), 4199-4210. https://doi.org/10.1111/bcp.15366

@article{cd9920b945384acc9f6a64efa573eb36,

title = "Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension",

abstract = "Aims: Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK. Methods: In this study, 53 832 and 43 106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD. Results: During a median follow-up of 2 years (interquartile range 1–5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2–2.6) and 2.2 (2.0–2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90–1.27] and 0.87 [0.71–1.07], respectively). Conclusion: We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.",

keywords = "Angiotensin-converting enzyme inhibitors, age-related macular degeneration, hypertension",

author = "Anuradhaa Subramanian and Diana Han and Tasanee Braithwaite and Rasiah Thayakaran and Zemedikun, {Dawit T} and Gokhale, {Krishna M} and Lee, {Wen Hwa} and Jesse Coker and Keane, {Pearse A} and Denniston, {Alastair K} and Krishnarajah Nirantharakumar and Laurent Azoulay and Adderley, {Nicola J}",

note = "Funding Information: Drs Adderley, Nirantharakumar and Denniston reported a grant from Action Against Age‐related Macular Degeneration during the conduct of the study. Dr Adderley reported receiving grants from Medical Research Council, National Institute for Health Research and National Institute for Health Research RfPB outside the submitted work. Dr Nirantharakumar reported receiving grants from Medical Research Council, National Institute for Health Research, AstraZeneca, MSD, Boehringer Ingelheim, Vifor, and Health Data Research UK and personal fees from Sanofi outside the submitted work. Dr Denniston reported receiving grant support from Health Data Research UK outside the submitted work. Dr Braithwaite reported receiving salary support from the patient charity Olivia's Vision. No other disclosures were reported. Publisher Copyright: {\textcopyright} 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.",

year = "2022",

month = sep,

doi = "10.1111/bcp.15366",

language = "English",

volume = "88",

pages = "4199--4210",

journal = "British Journal of Clinical Pharmacology",

issn = "0306-5251",

publisher = "Wiley",

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Subramanian, A, Han, D, Braithwaite, T, Thayakaran, R , Zemedikun, DT , Gokhale, KM, Lee, WH, Coker, J, Keane, PA, Denniston, AK , Nirantharakumar, K, Azoulay, L & Adderley, NJ 2022, 'Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension', British Journal of Clinical Pharmacology, vol. 88, no. 9, pp. 4199-4210. https://doi.org/10.1111/bcp.15366

TY - JOUR

T1 - Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension

AU - Subramanian, Anuradhaa

AU - Han, Diana

AU - Braithwaite, Tasanee

AU - Thayakaran, Rasiah

AU - Zemedikun, Dawit T

AU - Gokhale, Krishna M

AU - Lee, Wen Hwa

AU - Coker, Jesse

AU - Keane, Pearse A

AU - Denniston, Alastair K

AU - Nirantharakumar, Krishnarajah

AU - Azoulay, Laurent

AU - Adderley, Nicola J

N1 - Funding Information: Drs Adderley, Nirantharakumar and Denniston reported a grant from Action Against Age‐related Macular Degeneration during the conduct of the study. Dr Adderley reported receiving grants from Medical Research Council, National Institute for Health Research and National Institute for Health Research RfPB outside the submitted work. Dr Nirantharakumar reported receiving grants from Medical Research Council, National Institute for Health Research, AstraZeneca, MSD, Boehringer Ingelheim, Vifor, and Health Data Research UK and personal fees from Sanofi outside the submitted work. Dr Denniston reported receiving grant support from Health Data Research UK outside the submitted work. Dr Braithwaite reported receiving salary support from the patient charity Olivia's Vision. No other disclosures were reported. Publisher Copyright: © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

PY - 2022/9

Y1 - 2022/9

N2 - Aims: Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK. Methods: In this study, 53 832 and 43 106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD. Results: During a median follow-up of 2 years (interquartile range 1–5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2–2.6) and 2.2 (2.0–2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90–1.27] and 0.87 [0.71–1.07], respectively). Conclusion: We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.

AB - Aims: Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK. Methods: In this study, 53 832 and 43 106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD. Results: During a median follow-up of 2 years (interquartile range 1–5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2–2.6) and 2.2 (2.0–2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90–1.27] and 0.87 [0.71–1.07], respectively). Conclusion: We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.

KW - Angiotensin-converting enzyme inhibitors

KW - age-related macular degeneration

KW - hypertension

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U2 - 10.1111/bcp.15366

DO - 10.1111/bcp.15366

M3 - Article

C2 - 35474585

SN - 0306-5251

VL - 88

SP - 4199

EP - 4210

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

IS - 9

ER -

Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension

Abstract

Bibliographical note

Keywords

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