eprintid: 10107895
rev_number: 14
eprint_status: archive
userid: 608
dir: disk0/10/10/78/95
datestamp: 2020-08-17 10:54:09
lastmod: 2021-10-05 00:49:43
status_changed: 2020-08-17 10:54:09
type: article
metadata_visibility: show
creators_name: Morales, DR
creators_name: Morant, SV
creators_name: MacDonald, TM
creators_name: Hallas, J
creators_name: Ernst, MT
creators_name: Pottegard, A
creators_name: Herings, RMC
creators_name: Smits, E
creators_name: Overbeek, JA
creators_name: Mackenzie, IS
creators_name: Doney, ASF
creators_name: Mitchell, L
creators_name: Bennie, M
creators_name: Robertson, C
creators_name: Wei, L
creators_name: Nicholson, L
creators_name: Morris, C
creators_name: Flynn, RWV
title: Impact of EU regulatory label changes for diclofenac in people with cardiovascular disease in four countries: Interrupted time series regression analysis
ispublished: inpress
divisions: UCL
divisions: B02
divisions: C08
divisions: D10
divisions: G11
keywords: NSAIDs, cardiovascular disease, diclofenac, drug safety, epidemiology, pharmacovigilance
note: © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/).
abstract: OBJECTIVE: Due to cardiovascular safety concerns, the European Medicines Agency (EMA) recommended new contraindications and changes to product information for diclofenac across Europe in 2013. This study aims to measure their impact among targeted populations. METHOD: Quarterly interrupted time series regression (ITS) analyses of diclofenac initiation among cohorts with contraindications (congestive cardiac failure [CHF], ischaemic heart disease [IHD], peripheral arterial disease [PAD], cerebrovascular disease [CVD]) and cautions (hypertension, hyperlipidaemia, diabetes) from Denmark, the Netherlands, England and Scotland. RESULTS: The regulatory action was associated with significant immediate absolute reductions in diclofenac initiation in all countries for IHD (Denmark -0.08%, 95%CI -0.13, -0.03; England -0.09%, 95%CI -0.13 to -0.06%; the Netherlands -1.84%, 95%CI -2.51 to -1.17%; Scotland -0.34%, 95%CI -0.38 to -0.30%), PAD and hyperlipidaemia, the Netherlands, England and Scotland for hypertension and diabetes, and England and Scotland for CHF and CVD. Post-intervention there was a significant negative trend in diclofenac initiation in the Netherlands for IHD (-0.12%, 95%CI -0.19 to -0.04), PAD (-0.13%, 95%CI -0.22 to -0.05), hypertension, hyperlipidaemia and diabetes, and in Scotland for CHF (-0.01%, 95%CI -0.02 to -0.007%), IHD (-0.017, 95%CI -0.02, -0.01%), PAD and hypertension. In England, diclofenac initiation rates fell less steeply. In Denmark changes were more strongly associated with the earlier EMA 2012 regulatory action. CONCLUSION: Although significant reductions in diclofenac initiation occurred, patients with contraindications continued to be prescribed diclofenac, the extent of which varied by country and target condition. Understanding reasons for such variation may help to guide the design or dissemination of future safety warnings.
date: 2020-08-02
date_type: published
official_url: https://doi.org/10.1111/bcp.14478
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1800997
doi: 10.1111/bcp.14478
lyricists_name: Wei, Li
lyricists_id: LWEIX32
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: British Journal of Clinical Pharmacology
event_location: England
issn: 1365-2125
citation:        Morales, DR;    Morant, SV;    MacDonald, TM;    Hallas, J;    Ernst, MT;    Pottegard, A;    Herings, RMC;                                             ... Flynn, RWV; + view all <#>        Morales, DR;  Morant, SV;  MacDonald, TM;  Hallas, J;  Ernst, MT;  Pottegard, A;  Herings, RMC;  Smits, E;  Overbeek, JA;  Mackenzie, IS;  Doney, ASF;  Mitchell, L;  Bennie, M;  Robertson, C;  Wei, L;  Nicholson, L;  Morris, C;  Flynn, RWV;   - view fewer <#>    (2020)    Impact of EU regulatory label changes for diclofenac in people with cardiovascular disease in four countries: Interrupted time series regression analysis.                   British Journal of Clinical Pharmacology        10.1111/bcp.14478 <https://doi.org/10.1111/bcp.14478>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10107895/1/bcp.14478.pdf