Evaluating the Effectiveness of an Additional Risk Minimization Measure to Reduce the Risk of Prescribing Mirabegron to Patients with Severe Uncontrolled Hypertension in Four European Countries.

BACKGROUND

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%,

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.

Informations de copyright

© 2020 Heintjes et al.

Déclaration de conflit d'intérêts

Edith M. Heintjes, Irene D. Bezemer, Elisabeth Smits and Fernie J.A. Penning-van Beest performed this work as employees of the PHARMO Institute for Drug Outcomes Research. This independent research institute performs financially supported studies for government and related healthcare authorities and pharmaceutical companies. Daniel Prieto-Alhambra leads the Pharmaco- and Device Epidemiology research group at the Centre for Statistics in Medicine, Oxford University. Daniel Prieto-Alhambra also reports that Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA’s department and open for external participants. This group has received speaker fees and consultancy fees from Amgen and UCB, and research grants from Amgen, UCB, Les Laboratories Servier, Novartis, and Astellas. Ying (Helen) He is a postdoctoral research fellow at the Pharmaco- and Device Epidemiology research group at the Centre for Statistics in Medicine, Oxford University. Minna Vehkala and Fabian Hoti are employees of Statfinn – EPID Research, which performs commissioned pharmacoepidemiological studies; and thus their employees have been and currently are working in collaboration with several pharmaceutical companies. Daniel Dedman and Helen P. Booth are full time employees of CPRD, which provides contract research services for government and related healthcare authorities, and the pharmaceutical industry, including Astellas Pharma. Stefan de Vogel, Noah Jamie Robinson, and Kwame Appenteng are employees of Astellas. The authors report no other conflicts of interest in this work.