Measuring the Effectiveness of Safety Warnings on the Risk of Stroke in Older Antipsychotic Users: A Nationwide Cohort Study in Two Large Electronic Medical Records Databases in the United Kingdom and Italy
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Safety warnings relating to antipsychotic-associated stroke among older persons in the UK and Italy were issued. However, the impact of these safety warnings on stroke risk has not been measured to date.
The aim of this study was to measure the change in stroke incidence after two safety warnings in both the UK and Italy.
A cohort study was conducted using electronic medical records representative of the UK (The Health Improvement Network) and Italy (Health Search—IQVIA Health LPD), containing data on 11 million and 1 million patients, respectively. After each drug safety warning, elderly antipsychotic new initiators were propensity-score matched 1:1:1 on antipsychotic initiators before any safety warning. Stroke incidence within 6 months of antipsychotic initiation, using an intention-to-treat approach, was the main outcome.
In the UK and Italy, 6342 and 7587 elderly antipsychotic initiators were identified, respectively. A 42% stroke incidence reduction was seen in the UK after the first safety warning [42.3 (95% confidence interval (CI) 35.2–50.8) vs. 24.4 [95% CI 19.0–31.2] events per 1000 person-years (PYs)], while there was a 60% stroke incidence reduction after the second warning (16.9 [95% CI 12.2–23.4] events per 1000 PYs) compared to before the first warning. There was no significant reduction in stroke incidence in Italy.
Antipsychotic safety warnings were followed by a reduction in stroke incidence among older antipsychotic users in the UK, but not Italy.
Compliance with Ethical Standards
Conflict of interest
Janet Sultana, Andrea Fontana, Francesco Giorgianni, Silvia Tillati, Claudio Cricelli, Alessandro Pasqua, Elisabetta Patorno, Clive Ballard and Miriam Sturkenboom have no financial relationships with any organisations that might have had an interest in the submitted work over the previous 3 years, or no other relationships or activities that could appear to have influenced the submitted work. Over the last 3 years, Gianluca Trifirò has attended advisory boards on topics not related to this paper, organized by Sandoz, Hospira, Sanofi, Biogen, Ipsen and Shire, and is a consultant for Otsuka. He is principal investigator at the University of Messina of observational studies funded by several pharmaceutical companies (Amgen, AstraZeneca, Daiichi Sankyo, IBSA), as well as scientific coordinator of the Masters program ‘Pharmacovigilance, Pharmacoepidemiology and Pharmacoeconomics: Real-World Data Evaluations’ at the University of Messina, for which he receives unconditional funding from several pharmaceutical companies, including Takeda, Teva, Almirall, Shire, Novartis, Roche, Otsuka and Zambon.
This work was supported by a grant from the Italian Health Ministry held by Gianluca Trifiro’: [GR-2009-607316—Assessment of the Safety of Antipsychotic Drugs in Elderly with Dementia: An International, Population-Based Study Using Healthcare Databases. The funder played no role in study design, data collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the article for publication.
The use of THIN database was approved by the Cegidim Scientific Review Committee (SRC 13-085). Use of the Health Search—IQVIA Health LPD database was notified to the Ethics Committee of the University Hospital G. Martino of Messina. In Italy, full ethics approval is not required for retrospective observational studies with anonymised data. The authors declare that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
The data that support the findings of this study are available from third parties, i.e. the Erasmus Medical Centre for THIN and the Italian Society of General Practitioners/IQVIA for Health Search—IQVIA Health LPD. However, restrictions apply to the availability of these data, which were used under license for the current study and are therefore not publicly available. However, data are available from the authors upon reasonable request and with permission of the Erasmus Medical Centre and the Italian Society of General Practitioners/IQVIA.
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