Adverse Drug Reactions to Guideline-Recommended Heart Failure Drugs in Women: A Systematic Review of the Literature

Sophie H Bots, Floor Groepenhoff, Anouk L M Eikendal, Cara Tannenbaum, Paula A Rochon, Vera Regitz-Zagrosek, Virginia M Miller, Danielle Day, Folkert W Asselbergs, Hester M den Ruijter

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Pages (from-to)258-266
Number of pages9
JournalJACC. Heart failure
Issue number3
Publication statusPublished - Mar 2019


  • adverse drug reactions
  • heart failure
  • sex differences
  • sex-specific reporting
  • women


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