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Edith M Heintjes,1 Irene D Bezemer,1 Daniel Prieto-Alhambra,2,3 Elisabeth Smits,1 Helen P Booth,4 Daniel Dedman,4 Ying He,3 Fabian Hoti,5 Minna Vehkala,5 Stefan de Vogel,6 Noah Jamie Robinson,6 Kwame Appenteng,7 Fernie JA Penning-van Beest1 1PHARMO Institute for Drug Outcomes Research, Utrecht, the Netherlands; 2Idiap Jordi Gol Primary Care Research Institute and CIBERFes, Universitat Autonoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Catalonia, Spain; 3Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, England, UK; 4Clinical Practice Research Datalink (CPRD), London, UK; 5Statfinn - EPID Research, Espoo, Finland; 6Astellas Pharma Europe B.V., Leiden, Netherlands; 7Astellas Pharma Global Development, Inc., Northbrook, IL, USACorrespondence: Edith M HeintjesPHARMO Institute for Drug Outcomes Research, Van Deventerlaan 30-40, Utrecht, AE 3528, the NetherlandsTel +31 30 7440 800Email pharmo@pharmo.nlBackground: Mirabegron, indicated for the treatment of overactive bladder, is contraindicated in patients with severe uncontrolled hypertension (systolic blood pressure ≥ 180 mm Hg and/or diastolic blood pressure ≥ 110 mm Hg). In September 2015, a Direct Healthcare Professional Communication (DHPC) letter was disseminated as an additional risk minimisation measure.Purpose: To assess the effectiveness of the DHPC in reducing the proportions of patients with severe or non-severe uncontrolled hypertension at mirabegron initiation.Methods: An observational multi-database cohort study was undertaken using routinely collected healthcare data (December 2012–December 2016) from the PHARMO Database Network (Netherlands), SIDIAP database (Spain), CPRD (United Kingdom, UK) and national healthcare registers and electronic medical records from Finland. DHPC effectiveness was evaluated using interrupted time series analyses comparing trends and changes in monthly proportions of severe or non-severe uncontrolled hypertensive mirabegron initiations relative to the timing of the DHPC dissemination.Results: The study population comprised 52,078 patients. Prior to DHPC dissemination, across the four databases, 0.3– 1.3% had severe uncontrolled hypertension. Estimated absolute changes (EAC) in proportions of severe uncontrolled hypertension post-DHPC indicated a tendency towards a lower proportion in the Netherlands (EAC − 0.36%, p=0.053), unchanged proportions in Spain and the UK and a higher proportion in Finland (EAC +0.73%, p=0.016). For non-severe uncontrolled hypertension (13– 16% pre-DHPC), post-DHPC proportions tended to be lower in the Netherlands (EAC − 2.02%, p=0.038) and Spain (EAC − 1.04%, p=0.071), and unchanged in the UK and Finland.Conclusion: Severe uncontrolled hypertension prior to mirabegron initiation was uncommon in these four European countries even before DHPC dissemination. This suggests that other risk minimisation communications (prior to the DHPC dissemination) had worked adequately with respect to minimising mirabegron use among patients with severe uncontrolled hypertension. No strong and consistent evidence of further risk minimisation after the DHPC dissemination was observed in this study.Keywords: drug utilisation study, direct healthcare professional communication, risk minimization, interrupted time series analysis |
