Adverse Drug Reactions to Guideline-Recommended Heart Failure Drugs in Women

ISS Fro Ne the Ins Ca Ge Ce Me He Inf (20 Ro the is Re thi Ma 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, b-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 b-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. (J Am Coll Cardiol HF 2019;7:258–66) © 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). N 2213-1779 https://doi.org/10.1016/j.jchf. 2019.01. 009 m the Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the therlands; Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Faculties of Pharmacy and Medicine, Université de Montréal, Montréal, Canada; Women’s College Research titute, Women’s College Hospital, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, nada; Institute for Gender in Medicine and Center for Cardiovascular Research, Charite, University Medicine Berlin, Berlin, rmany; DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany; Women’s Health Research nter, Mayo Clinic, Rochester, Minnesota; UniQure, Amsterdam, the Netherlands; Department of Cardiology, University dical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Institute of Cardiovascular Science, Faculty of Popular alth Sciences, University College London, London, United Kingdom; and the Health Data Research UK and Institute of Health ormatics, University College London, London, United Kingdom. This study was funded by the Dutch Heart Foundation 13T084, Queen of Hearts Program) and by ZonMw grant (849100003, Reviews en Kennissyntheses Gender en Gezondheid). Dr. chon holds the Retired Teachers of Ontario/les Enseignantes et Enseignants Retraités de l’Ontario Chair in Geriatric Medicine at University of Toronto. Dr. Regitz-Zagrosek has reported receiving speaker’s honoraria from Pfizer and Berlin Chemie. Dr. Day an employee of UniQure. Dr. Asselbergs is supported by University College London Hospitals National Institute for Health search Biomedical Research Centre. All other authors have reported that they have no relationships relevant to the contents of s paper to disclose. nuscript received November 30, 2018; revised manuscript received January 15, 2019, accepted January 16, 2019. J A C C : H E A R T F A I L U R E V O L . 7 , N O . 3 , 2 0 1 9 Bots et al. M A R C H 2 0 1 9 : 2 5 8 – 6 6 Adverse Drug Reactions to Heart Failure Drugs in Women 259 AB BR E V I A T I O N S