European Journal of Clinical Pharmacology

, Volume 74, Issue 2, pp 193–199 | Cite as

Comparison of cardiovascular events among treatments for overactive bladder: a Danish nationwide cohort study

  • Andrea V. Margulis
  • Jesper Hallas
  • Anton Pottegård
  • Nina Sahlertz Kristiansen
  • Willem Jan Atsma
  • Billy Franks
  • Milbhor D’Silva
  • Cristina Varas-Lorenzo
  • Susana Perez-Gutthann
  • Alejandro Arana
Pharmacoepidemiology and Prescription



The purpose of this study is to explore the cardiovascular safety of antimuscarinic drugs to treat overactive bladder (OAB) in Denmark.


This was a cohort study using data recorded in Danish registries from patients newly exposed to darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium in 2004–2012. We estimated crude and standardized incidence rates (IRs) for acute myocardial infarction (AMI); stroke; cardiovascular mortality; major adverse cardiac events (MACE, a combined endpoint of the previous three outcomes); and all-cause death for the individual and combined drugs. We also estimated crude, standardized, and propensity score-stratified incidence rate ratios (IRRs) comparing individual antimuscarinic drugs to tolterodine as the reference.


Among 72,917 new users of OAB drugs (mean age, 66 years; 60% women), the standardized IR (95% confidence interval) per 1000 person-years for current use of any OAB drug was 2.7 (2.5–2.9) for AMI, 1.3 (1.2–1.5) for stroke, 7.8 (7.5–8.1) for MACE, 4.8 (4.5–5.0) for cardiovascular mortality, and 15.2 (14.8–15.6) for all-cause mortality. Propensity score-stratified IRRs for current use (reference, tolterodine) were close to the null for all drugs and endpoints.


We did not identify differences in the risk of cardiovascular events or mortality among users of individual antimuscarinic OAB drugs.


Denmark Pharmacoepidemiology Urinary bladder, overactive Cardiovascular diseases Muscarinic antagonists 



We would like to thank Adele Monroe and Whitney Krueger from RTI Health Solutions for their help preparing the manuscript, Morten Olesen from the University of Southern Denmark with assistance during data analysis, and Stefan de Vogel and Kwame Appenteng from Astellas for their input during the study.

Author’s contributions

All authors fulfilled the ICMJE authorship criteria. Additionally, the authors were involved as follows: substantial contribution to the design of the study: AVM, JH, AP, NSK, WJA, CVL, SPG and AA; acquisition and analysis of the data: JH, AP, NSK; interpretation of the data: all authors; drafting or revising critically for important intellectual content: all authors; final approval: all authors; agreement to be accountable for all parts of the work: all authors.

Compliance with ethical standards

Ethical approval

Retrospective registry studies do not require ethics committee notification or approval, since they do not fall under the Danish definition of health science research.

Conflict of interest

The study was funded by Astellas Pharma Global Development, Inc., of which Willem Jan Atsma, Billy Franks, and Milbhor D’Silva are employees. Andrea Margulis, Alejandro Arana, and Susana Perez-Gutthann are full-time employees of RTI International, an independent non-profit research organization that does work for government agencies and pharmaceutical companies. Cristina Varas-Lorenzo was a full-time employee of RTI International at the time of the conduct of the study. Jesper Hallas, Nina Sahlertz. Kristiansen, and Anton Pottegård have worked on a project commissioned by Astellas, with funding paid to their employer. The contract granted the research team independent publication rights.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Andrea V. Margulis
    • 1
  • Jesper Hallas
    • 2
  • Anton Pottegård
    • 2
  • Nina Sahlertz Kristiansen
    • 2
  • Willem Jan Atsma
    • 3
  • Billy Franks
    • 3
  • Milbhor D’Silva
    • 4
  • Cristina Varas-Lorenzo
    • 1
  • Susana Perez-Gutthann
    • 1
  • Alejandro Arana
    • 1
  1. 1.RTI Health SolutionsBarcelonaSpain
  2. 2.University of Southern DenmarkOdenseDenmark
  3. 3.Astellas Pharma B.V.LeidenThe Netherlands
  4. 4.Astellas Pharma Global Development Inc.NorthbrookUSA

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