Author + information
- Received November 30, 2018
- Revision received January 15, 2019
- Accepted January 16, 2019
- Published online February 25, 2019.
- Sophie H. Bots, MSca,
- Floor Groepenhoff, MDb,
- Anouk L.M. Eikendal, MD, PhDa,
- Cara Tannenbaum, MD, MScc,
- Paula A. Rochon, MD, MPHd,e,
- Vera Regitz-Zagrosek, PhDf,g,
- Virginia M. Miller, PhDh,
- Danielle Day, PhDi,
- Folkert W. Asselbergs, MD, PhDj,k,l and
- Hester M. den Ruijter, PhDa,∗ (, )@InnovatieHester
- aLaboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
- bLaboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
- cFaculties of Pharmacy and Medicine, Université de Montréal, Montréal, Canada
- dWomen’s College Research Institute, Women’s College Hospital, Toronto, Canada
- eDalla Lana School of Public Health, University of Toronto, Toronto, Canada
- fInstitute for Gender in Medicine and Center for Cardiovascular Research, Charite, University Medicine Berlin, Berlin, Germany
- gDZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany
- hWomen’s Health Research Center, Mayo Clinic, Rochester, Minnesota
- iUniQure, Amsterdam, the Netherlands
- jDepartment of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
- kInstitute of Cardiovascular Science, Faculty of Popular Health Sciences, University College London, London, United Kingdom
- lHealth Data Research UK and Institute of Health Informatics, University College London, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Hester den Ruijter, Laboratory of Experimental Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, the Netherlands.
Objectives This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication.
Background Women are more likely to experience ADRs than men, and these reactions may negatively affect women’s immediate and long-term health. HF in particular is associated with increased ADR risk because of the high number of comorbidities and older age. However, little is known about ADRs in women with HF who are treated with guideline-recommended drugs.
Methods A systematic search of PubMed and EMBASE was performed to collect all available information on ADRs to angiotensin-converting enzyme inhibitors, β-blockers, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, ivabradine, and digoxin in both women and men with HF.
Results The search identified 155 eligible records, of which only 11 (7%) reported ADR data for women and men separately. Sex-stratified reporting of ADRs did not increase over the last decades. Six of the 11 studies did not report sex differences. Three studies reported a higher risk of angiotensin-converting enzyme inhibitor–related ADRs in women, 1 study showed higher digoxin-related mortality risk for women, and 1 study reported a higher risk of mineralocorticoid receptor antagonist–related ADRs in men. No sex differences in ADRs were reported for angiotensin II receptor blockers and β-blockers. Sex-stratified data were not available for ivabradine.
Conclusions These results underline the scarcity of ADR data stratified by sex. The study investigators call for a change in standard scientific practice toward reporting of ADR data for women and men separately.
This study was funded by the Dutch Heart Foundation (2013T084, Queen of Hearts Program) and by ZonMw grant (849100003, Reviews en Kennissyntheses Gender en Gezondheid). Dr. Rochon holds the Retired Teachers of Ontario/les Enseignantes et Enseignants Retraités de l’Ontario Chair in Geriatric Medicine at the University of Toronto. Dr. Regitz-Zagrosek has reported receiving speaker’s honoraria from Pfizer and Berlin Chemie. Dr. Day is an employee of UniQure. Dr. Asselbergs is supported by University College London Hospitals National Institute for Health Research Biomedical Research Centre. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 30, 2018.
- Revision received January 15, 2019.
- Accepted January 16, 2019.
- 2019 The Authors