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

Veena Hoffman, Jesper Hallas, Marie Linder, Andrea Margulis, Brandon T. Suehs, Alejandro Arana, Kelesitse Phiri, Cheryl Enger, Libby Horter, Ingvild Odsbu, Morten Olesen, Susana Perez-Gutthann, Yihua Xu, Nina Sahlertz Kristiansen, Kwame Appenteng, Stefan de Vogel, John D. Seeger*, the mirabegron PMR-PASS study group

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Introduction: During clinical trials, mirabegron, a β3-adrenoreceptor agonist, was associated with increased vital signs vs placebo in patients with overactive bladder. Objective: The purpose of this study was to compare incidence rates of adverse cardiovascular (CV) outcomes following mirabegron or antimuscarinic use. Methods: We conducted an observational post-marketing safety study utilising real-world data. The study population was identified within five sources: Danish and Swedish National Registers, Clinical Practice Research Datalink (UK), Optum (USA) and Humana (USA). Episodes of time when patients were new users of mirabegron or antimuscarinics (October 2012–December 2018) were sourced from prescriptions and matched on propensity scores. Occurrences of major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), stroke, CV mortality and all-cause mortality were identified. Outcome incidence rates and hazard ratios from Cox models were estimated. Results: Overall, 152,026 mirabegron and 152,026 antimuscarinic episodes were matched. The population consisted of 63.1% women and 72.6% were ≥ 65 years old. There were no appreciable differences in the incidence rates of MACE, AMI or stroke between users of mirabegron and antimuscarinics. Incidence rates of CV mortality (hazard ratio 0.83, 95% confidence interval 0.73–0.95) and all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76–0.84) were no higher with mirabegron vs antimuscarinics. Results restricted to episodes at high risk for CV events or stratified by age (< 65 years, ≥ 65 years) or prior overactive bladder medication use were consistent with overall findings. Conclusions: This large, multinational study found no higher risk of MACE, AMI, stroke, CV mortality or all-cause mortality among users of mirabegron relative to users of antimuscarinics.

OriginalsprogEngelsk
TidsskriftDrug Safety
Vol/bind44
Udgave nummer8
Sider (fra-til)899-915
ISSN0114-5916
DOI
StatusUdgivet - aug. 2021

Bibliografisk note

Funding Information:
This study was funded by Astellas Pharma Inc.

Funding Information:
Medical writing support was provided by Michael Parsons from Envision and funded by the study sponsor. The authors acknowledge all of the members of the mirabegron PMR-PASS study group: Cheryl Enger, John Seeger (Optum), Veena Hoffman (former Optum employee) and Kelesitse Phiri (former Optum employee); Jesper Hallas, Morten Olesen (University of Southern Denmark) and Nina Sahlertz Kristiansen (former University of Southern Denmark employee); Shahram Bahmanyar, Marie Linder, Helle Kieler (Centre for Pharmacoepidemiology, Karolinska Institutet) and Ingvild Odsbu (former Centre for Pharmacoepidemiology, Karolinska Institutet employee); Alejandro Arana, Lisa McQuay, Andrea Margulis, Susana Perez-Gutthann and Ryan Ziemiecki (RTI Health Solutions); Su Bunniran, Brandon Suehs, Claudia Uribe, Yihua Xu (Humana Healthcare Research) and Libby Horter (former Humana Healthcare Research employee); Kwame Appenteng, Stefan de Vogel, Noah Jamie Robinson, Songlin Xue, Josie Wolfram, Achim Steup, Jena Giese-Pagac, Raymond van Aarle, Neha Sheth, David Burns, Natalie Boone, Mary Beth Blauwet (Astellas Pharma), Milbhor D?Silva (former Astellas employee), Billy Franks (former Astellas employee), Willem Jan Atsma (former Astellas employee) and Tim Auton (posthumously; former Astellas employee) and Edeltraut Garbe, Anders Ekbom, Todd Lee, Noel Weiss and John Rumsfeld (Scientific Advisory Board). Additional thanks are due to Sara Yuewen Gao, Laura Karslake, Nan Liu, Katherine Reed, Bruce Turnbull, Jing Yang (Optum), Nicole Brooks (former Optum employee) and Kathleen Mortimer (former Optum employee). This study is based in part on data from the Clinical Practice Research Datalink obtained under license from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by patients and collected by the National Health Service (NHS)?as part of their care and support. The interpretation and conclusions contained in this study are those of the authors alone. Copyright ? (2018), re-used with the permission of The Health & Social Care Information Centre. All rights reserved.

Funding Information:
Cheryl Enger and John D. Seeger are employees of Optum. Veena Hoffman and Kelesitse Phiri were employees of Optum at the time the study was conducted. Veena Hoffman, Kelesitse Phiri, Cheryl Enger and John D. Seeger hold stock in UnitedHealth Group, Optum’s parent company. UnitedHealthcare, a UnitedHealth subsidiary, is a major purchaser of pharmaceutical products. The work was funded with a research contract between Optum and Astellas. Jesper Hallas and Morten Olesen have worked on a project commissioned by Astellas, with funding paid to their employer, the University of Southern Denmark. Nina Sahlertz Kristiansen was an employee of the University of Southern Denmark at the time the study was conducted. The contract granted the research team at the University of Southern Denmark independent publication rights. Marie Linder is an employee of the Centre for Pharmacoepidemiology, Karolinska Institutet. Ingvild Odsbu was an employee of the Centre for Pharmacoepidemiology at the time the study was conducted. The Centre receives grants from several entities (pharmaceutical companies, regulatory authorities and contract research organisations), including Astellas and Pfizer, for performance of drug safety and drug utilisation studies. Andrea V. Margulis, Alejandro Arana and Susana Perez-Gutthann are employees of RTI Health Solutions. RTI Health Solutions is a unit of RTI International, an independent non-profit organisation that conducts work for government, public and private organisations, including pharmaceutical companies. The RTI authors participated in this work in the course of employment as work for hire, pursuant to a contract to conduct an independent research study for a client (Astellas). The authors received no compensation other than their annual salary from their employer. Brandon T. Suehs and Yihua Xu are employees of Humana Healthcare Research, which received funding from Astellas in connection with the performance of this study. Libby Horter was an employee of Humana Healthcare Research at the time the study was conducted. Kwame Appenteng and Stefan de Vogel are employees of Astellas.

Funding Information:
Medical writing support was provided by Michael Parsons from Envision and funded by the study sponsor. The authors acknowledge all of the members of the mirabegron PMR-PASS study group: Cheryl Enger, John Seeger (Optum), Veena Hoffman (former Optum employee) and Kelesitse Phiri (former Optum employee); Jesper Hallas, Morten Olesen (University of Southern Denmark) and Nina Sahlertz Kristiansen (former University of Southern Denmark employee); Shahram Bahmanyar, Marie Linder, Helle Kieler (Centre for Pharmacoepidemiology, Karolinska Institutet) and Ingvild Odsbu (former Centre for Pharmacoepidemiology, Karolinska Institutet employee); Alejandro Arana, Lisa McQuay, Andrea Margulis, Susana Perez-Gutthann and Ryan Ziemiecki (RTI Health Solutions); Su Bunniran, Brandon Suehs, Claudia Uribe, Yihua Xu (Humana Healthcare Research) and Libby Horter (former Humana Healthcare Research employee); Kwame Appenteng, Stefan de Vogel, Noah Jamie Robinson, Songlin Xue, Josie Wolfram, Achim Steup, Jena Giese-Pagac, Raymond van Aarle, Neha Sheth, David Burns, Natalie Boone, Mary Beth Blauwet (Astellas Pharma), Milbhor D’Silva (former Astellas employee), Billy Franks (former Astellas employee), Willem Jan Atsma (former Astellas employee) and Tim Auton (posthumously; former Astellas employee) and Edeltraut Garbe, Anders Ekbom, Todd Lee, Noel Weiss and John Rumsfeld (Scientific Advisory Board). Additional thanks are due to Sara Yuewen Gao, Laura Karslake, Nan Liu, Katherine Reed, Bruce Turnbull, Jing Yang (Optum), Nicole Brooks (former Optum employee) and Kathleen Mortimer (former Optum employee). This study is based in part on data from the Clinical Practice Research Datalink obtained under license from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by patients and collected by the National Health Service (NHS) as part of their care and support. The interpretation and conclusions contained in this study are those of the authors alone. Copyright © (2018), re-used with the permission of The Health & Social Care Information Centre. All rights reserved.

Publisher Copyright:
© 2021, The Author(s).

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