<p>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</p>

Abstract

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%, 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.

Cardiovascular Risk in Users of Mirabegron Compared with Users of Antimuscarinic Treatments for Overactive Bladder: Findings from a Non-Interventional, Multinational, Cohort Study

“…Therefore, we did not conduct analyses to assess the effect of uncontrolled hypertension on the CV outcomes in this study. Furthermore, a European study that assessed the effectiveness of a direct healthcare communication letter to decrease the proportion of patients with uncontrolled hypertension prior to mirabegron initiation found that uncontrolled hypertension was uncommon before starting treatment with mirabegron even before the dissemination of the letter [ 39 ]. While it is possible that mirabegron might have influenced hypertension control in some patients, the previously mentioned results indicate that mirabegron initiation is quite rare in patients with uncontrolled hypertension, so there would be little to be learned from this type of analysis.…”

Pooling of primary care electronic health record (EHR) data on Huntington’s disease (HD) and cancer: establishing comparability of two large UK databases

“…Other studies have combined data from CPRD GOLD and CPRD Aurum without presenting direct comparisons between the databases, making it difficult to gauge the potential impact of heteregeneity. These include studies of incidence and prevalence study of rare conditions including juvenile idiopathic arthritis between 2000 and 2018,47 and neuromuscular conditions between 2000 and 201948; and a multicountry study examining the impact of a regulatory intervention to reduce inappropriate prescribing of mirabegron (a treatment for overactive bladder) to new users with severe or uncontrolled hypertension 49…”

“…These include studies of incidence and prevalence study of rare conditions including juvenile idiopathic arthritis between 2000 and 2018, 47 and neuromuscular conditions between 2000 and 2019 48 ; and a multicountry study examining the impact of a regulatory intervention to reduce inappropriate prescribing of mirabegron (a treatment for overactive bladder) to new users with severe or uncontrolled hypertension. 49 Other studies have used and compared data from CPRD GOLD and the QResearch database, which is also derived from EMIS primary care systems, and found baseline characteristics in patients with other conditions to be generally similar. [50][51][52][53][54] Strengths and limitations To our knowledge, this is the first published comparison of CPRD GOLD and CPRD Aurum to include both long-term incidence trends and detailed patient characteristics for specific conditions, and the first to include comparisons from a subset of overlapping practices in each database.…”