Impact of regulatory interventions to restrict the combined use of renin–angiotensin system blockers: A Danish nationwide drug utilisation study

Per Sindahl; Richard Ofori-Asenso; Christine Erikstrup Hallgreen; Kaare Kemp; Helga Gardarsdottir; Marie Louise De Bruin

doi:10.1111/bcp.15080

Impact of regulatory interventions to restrict the combined use of renin–angiotensin system blockers: A Danish nationwide drug utilisation study

Per Sindahl^*
, Richard Ofori-Asenso
, Christine Erikstrup Hallgreen
, Kaare Kemp
, Helga Gardarsdottir
, Marie Louise De Bruin

^*Corresponding author for this work

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

Abstract

This study aimed to evaluate the impact of the risk minimisation measures issued by the European Medicines Agency in 2014 to restrict the combined use of renin–angiotensin system (RAS) blocking agents in Denmark. Data from the Danish National Prescription Registry covering all medications dispensed during January 2008–December 2018 was used. The outcome was monthly prevalence of patients codispensed RAS blockers. Autoregressive integrated moving average interrupted time series regression was used to evaluate dispensing trends. The prevalence of patients codispensed RAS blockers decreased from 0.01 to 0.0003%. Preintervention trend was declining and further decreased with an additional −0.45 (95% confidence interval −0.66, −0.25) codispensing per million population after the intervention. Overall, the intervention had minimal impact on the combined use of RAS blockers. However, as the combined use of RAS blockers is low, further interventions to restrict the combined use of RAS blockers may not be required in Denmark at this point.

Original language	English
Pages (from-to)	1379-1384
Number of pages	6
Journal	British Journal of Clinical Pharmacology
Volume	88
Issue number	3
Early online date	13 Sept 2021
DOIs	https://doi.org/10.1111/bcp.15080
Publication status	Published - Mar 2022

Bibliographical note

Funding Information:
P.S., M.L.D.B., K.K., R.O.‐A., C.E.H. and H.G. report no conflict of interest. At time of the project, R.O.‐A., C.E.H. and M.L.D.W. were employed by Copenhagen Centre for Regulatory Sciences (CORS). CORS is a cross‐faculty university anchored institution involving various public (Danish Medicines Agency, Copenhagen University) and private stakeholders (Novo Nordisk, Lundbeck, Ferring Pharmaceuticals, LEO Pharma) as well as patient organizations (Rare Diseases Denmark). The centre is purely devoted to the scientific aspects of the regulatory field and with a patient‐oriented focus and the research is not company‐specific product or directly company related. In the last 5 years, CORS has received funding from Novo Nordisk, Lundbeck, Ferring Pharmaceuticals and LEO pharma for projects not related to this study. Currently, M.L.D.B. and H.G. are employed by Utrecht University and conduct research under the umbrella of the Utrecht‐WHO Collaborating Centre for Pharmaceutical Policy and Regulation. This Centre receives no direct funding or donations from private parties, including pharma industry. Research funding from public–private partnerships, e.g. IMI, The Escher Project ( http://escher.lygature.org/ ) is accepted under the condition that no company‐specific product or company related study is conducted. The Centre has received unrestricted research funding from public sources, e.g. World Health Organisation (WHO), Netherlands Organisation for Health Research and Development (ZonMW), the Dutch National Health Care Institute (ZIN), EC Horizon 2020, the Dutch Medicines Evaluation Board (MEB) and the Dutch Ministry of Health. R.O.‐A. is currently employed by Roche, UK.

Publisher Copyright:
© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Funding

P.S., M.L.D.B., K.K., R.O.‐A., C.E.H. and H.G. report no conflict of interest. At time of the project, R.O.‐A., C.E.H. and M.L.D.W. were employed by Copenhagen Centre for Regulatory Sciences (CORS). CORS is a cross‐faculty university anchored institution involving various public (Danish Medicines Agency, Copenhagen University) and private stakeholders (Novo Nordisk, Lundbeck, Ferring Pharmaceuticals, LEO Pharma) as well as patient organizations (Rare Diseases Denmark). The centre is purely devoted to the scientific aspects of the regulatory field and with a patient‐oriented focus and the research is not company‐specific product or directly company related. In the last 5 years, CORS has received funding from Novo Nordisk, Lundbeck, Ferring Pharmaceuticals and LEO pharma for projects not related to this study. Currently, M.L.D.B. and H.G. are employed by Utrecht University and conduct research under the umbrella of the Utrecht‐WHO Collaborating Centre for Pharmaceutical Policy and Regulation. This Centre receives no direct funding or donations from private parties, including pharma industry. Research funding from public–private partnerships, e.g. IMI, The Escher Project ( http://escher.lygature.org/ ) is accepted under the condition that no company‐specific product or company related study is conducted. The Centre has received unrestricted research funding from public sources, e.g. World Health Organisation (WHO), Netherlands Organisation for Health Research and Development (ZonMW), the Dutch National Health Care Institute (ZIN), EC Horizon 2020, the Dutch Medicines Evaluation Board (MEB) and the Dutch Ministry of Health. R.O.‐A. is currently employed by Roche, UK.

Keywords

angiotensin II receptor blockers
angiotensin-converting enzyme inhibitors
drug safety
drug utilisation
pharmacovigilance
renin–angiotensin system
risk management

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Brit J Clinical Pharma - 2021 - Sindahl - Impact of regulatory interventions to restrict the combined use of reninFinal published version, 579 KBLicence: CC BY-NC-ND

Cite this

@article{e6375a87ead049768d5553b67e9976f6,

title = "Impact of regulatory interventions to restrict the combined use of renin–angiotensin system blockers: A Danish nationwide drug utilisation study",

abstract = "This study aimed to evaluate the impact of the risk minimisation measures issued by the European Medicines Agency in 2014 to restrict the combined use of renin–angiotensin system (RAS) blocking agents in Denmark. Data from the Danish National Prescription Registry covering all medications dispensed during January 2008–December 2018 was used. The outcome was monthly prevalence of patients codispensed RAS blockers. Autoregressive integrated moving average interrupted time series regression was used to evaluate dispensing trends. The prevalence of patients codispensed RAS blockers decreased from 0.01 to 0.0003\%. Preintervention trend was declining and further decreased with an additional −0.45 (95\% confidence interval −0.66, −0.25) codispensing per million population after the intervention. Overall, the intervention had minimal impact on the combined use of RAS blockers. However, as the combined use of RAS blockers is low, further interventions to restrict the combined use of RAS blockers may not be required in Denmark at this point.",

keywords = "angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, drug safety, drug utilisation, pharmacovigilance, renin–angiotensin system, risk management",

author = "Per Sindahl and Richard Ofori-Asenso and Hallgreen, \{Christine Erikstrup\} and Kaare Kemp and Helga Gardarsdottir and \{De Bruin\}, \{Marie Louise\}",

note = "Funding Information: P.S., M.L.D.B., K.K., R.O.‐A., C.E.H. and H.G. report no conflict of interest. At time of the project, R.O.‐A., C.E.H. and M.L.D.W. were employed by Copenhagen Centre for Regulatory Sciences (CORS). CORS is a cross‐faculty university anchored institution involving various public (Danish Medicines Agency, Copenhagen University) and private stakeholders (Novo Nordisk, Lundbeck, Ferring Pharmaceuticals, LEO Pharma) as well as patient organizations (Rare Diseases Denmark). The centre is purely devoted to the scientific aspects of the regulatory field and with a patient‐oriented focus and the research is not company‐specific product or directly company related. In the last 5 years, CORS has received funding from Novo Nordisk, Lundbeck, Ferring Pharmaceuticals and LEO pharma for projects not related to this study. Currently, M.L.D.B. and H.G. are employed by Utrecht University and conduct research under the umbrella of the Utrecht‐WHO Collaborating Centre for Pharmaceutical Policy and Regulation. This Centre receives no direct funding or donations from private parties, including pharma industry. Research funding from public–private partnerships, e.g. IMI, The Escher Project ( http://escher.lygature.org/ ) is accepted under the condition that no company‐specific product or company related study is conducted. The Centre has received unrestricted research funding from public sources, e.g. World Health Organisation (WHO), Netherlands Organisation for Health Research and Development (ZonMW), the Dutch National Health Care Institute (ZIN), EC Horizon 2020, the Dutch Medicines Evaluation Board (MEB) and the Dutch Ministry of Health. R.O.‐A. is currently employed by Roche, UK. Publisher Copyright: {\textcopyright} 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley \& Sons Ltd on behalf of British Pharmacological Society.",

year = "2022",

month = mar,

doi = "10.1111/bcp.15080",

language = "English",

volume = "88",

pages = "1379--1384",

journal = "British Journal of Clinical Pharmacology",

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}

Impact of regulatory interventions to restrict the combined use of renin–angiotensin system blockers: A Danish nationwide drug utilisation study. / Sindahl, Per; Ofori-Asenso, Richard; Hallgreen, Christine Erikstrup et al.
In: British Journal of Clinical Pharmacology, Vol. 88, No. 3, 03.2022, p. 1379-1384.

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

TY - JOUR

T1 - Impact of regulatory interventions to restrict the combined use of renin–angiotensin system blockers

T2 - A Danish nationwide drug utilisation study

AU - Sindahl, Per

AU - Ofori-Asenso, Richard

AU - Hallgreen, Christine Erikstrup

AU - Kemp, Kaare

AU - Gardarsdottir, Helga

AU - De Bruin, Marie Louise

N1 - Funding Information: P.S., M.L.D.B., K.K., R.O.‐A., C.E.H. and H.G. report no conflict of interest. At time of the project, R.O.‐A., C.E.H. and M.L.D.W. were employed by Copenhagen Centre for Regulatory Sciences (CORS). CORS is a cross‐faculty university anchored institution involving various public (Danish Medicines Agency, Copenhagen University) and private stakeholders (Novo Nordisk, Lundbeck, Ferring Pharmaceuticals, LEO Pharma) as well as patient organizations (Rare Diseases Denmark). The centre is purely devoted to the scientific aspects of the regulatory field and with a patient‐oriented focus and the research is not company‐specific product or directly company related. In the last 5 years, CORS has received funding from Novo Nordisk, Lundbeck, Ferring Pharmaceuticals and LEO pharma for projects not related to this study. Currently, M.L.D.B. and H.G. are employed by Utrecht University and conduct research under the umbrella of the Utrecht‐WHO Collaborating Centre for Pharmaceutical Policy and Regulation. This Centre receives no direct funding or donations from private parties, including pharma industry. Research funding from public–private partnerships, e.g. IMI, The Escher Project ( http://escher.lygature.org/ ) is accepted under the condition that no company‐specific product or company related study is conducted. The Centre has received unrestricted research funding from public sources, e.g. World Health Organisation (WHO), Netherlands Organisation for Health Research and Development (ZonMW), the Dutch National Health Care Institute (ZIN), EC Horizon 2020, the Dutch Medicines Evaluation Board (MEB) and the Dutch Ministry of Health. R.O.‐A. is currently employed by Roche, UK. Publisher Copyright: © 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

PY - 2022/3

Y1 - 2022/3

N2 - This study aimed to evaluate the impact of the risk minimisation measures issued by the European Medicines Agency in 2014 to restrict the combined use of renin–angiotensin system (RAS) blocking agents in Denmark. Data from the Danish National Prescription Registry covering all medications dispensed during January 2008–December 2018 was used. The outcome was monthly prevalence of patients codispensed RAS blockers. Autoregressive integrated moving average interrupted time series regression was used to evaluate dispensing trends. The prevalence of patients codispensed RAS blockers decreased from 0.01 to 0.0003%. Preintervention trend was declining and further decreased with an additional −0.45 (95% confidence interval −0.66, −0.25) codispensing per million population after the intervention. Overall, the intervention had minimal impact on the combined use of RAS blockers. However, as the combined use of RAS blockers is low, further interventions to restrict the combined use of RAS blockers may not be required in Denmark at this point.

AB - This study aimed to evaluate the impact of the risk minimisation measures issued by the European Medicines Agency in 2014 to restrict the combined use of renin–angiotensin system (RAS) blocking agents in Denmark. Data from the Danish National Prescription Registry covering all medications dispensed during January 2008–December 2018 was used. The outcome was monthly prevalence of patients codispensed RAS blockers. Autoregressive integrated moving average interrupted time series regression was used to evaluate dispensing trends. The prevalence of patients codispensed RAS blockers decreased from 0.01 to 0.0003%. Preintervention trend was declining and further decreased with an additional −0.45 (95% confidence interval −0.66, −0.25) codispensing per million population after the intervention. Overall, the intervention had minimal impact on the combined use of RAS blockers. However, as the combined use of RAS blockers is low, further interventions to restrict the combined use of RAS blockers may not be required in Denmark at this point.

KW - angiotensin II receptor blockers

KW - angiotensin-converting enzyme inhibitors

KW - drug safety

KW - drug utilisation

KW - pharmacovigilance

KW - renin–angiotensin system

KW - risk management

UR - https://www.scopus.com/pages/publications/85116530442

U2 - 10.1111/bcp.15080

DO - 10.1111/bcp.15080

M3 - Article

C2 - 34519065

AN - SCOPUS:85116530442

SN - 0306-5251

VL - 88

SP - 1379

EP - 1384

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

IS - 3

ER -

Impact of regulatory interventions to restrict the combined use of renin–angiotensin system blockers: A Danish nationwide drug utilisation study

Abstract

Bibliographical note

Funding

Keywords

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