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Sex differences in heart failure and precision medicine: right patient, right time…wrong dose?
  1. Rana Hassan1,
  2. Sofia B Ahmed1,2
  1. 1 Department of Medicine, University of Calgary, Calgary, Alberta, Canada
  2. 2 Libin Cardiovascular Institute, Calgary, Alberta, Canada
  1. Correspondence to Dr Sofia B Ahmed, University of Calgary, Calgary, Canada; Sofia.Ahmed{at}

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Heart failure (HF) affects women and men differently, in part due to sex-related differences in disease aetiology and pathophysiology, which may ultimately impact treatment response and outcomes. Sex differences in HF outcomes may be further exacerbated by differences in medication pharmacokinetics and pharmacodynamics, with female-specific physiological factors including lower body mass, as well as decreased renal excretion and gastrointestinal enzymatic activity, leading to higher medication bioavailability. As a result, the administration of sex-neutral medication doses leads to greater drug exposure in female patients, which may subsequently lead to a higher incidence of adverse drug reactions.1 This raises the possibility of sex-based HF treatments to improve clinical outcomes. However, current guidelines adopt a ‘one size fits all’ approach, with an emphasis on target-dosed therapy. In this era of precision medicine, is it time to redefine optimal HF therapy based on the sex of the patient?

Bots and colleagues2 evaluated the associations between prescription practice and survival of patients with HF in a community setting using electronic health record data from the Cardiology Centre of the Netherlands database. This well-designed study included over 1000 patients with de novo HF treated with at least one guideline HF medication with a median follow-up time of 3.7 years. The main outcome was all-cause mortality in relation to the prescribed HF medication dose (reference ≥50% target dose), stratified by sex and HF type. The authors concluded that lower angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) dose was associated with improved survival in women, but not in men, with HF with reduced ejection fraction (HFrEF). In contrast, no ACEI/ARB dose–survival association was observed in patients with HF with preserved ejection fraction (HFpEF) of either sex. No association was observed between beta-blocker dose and mortality in any of the prespecified subgroups.

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  • Contributors RH and SA both contributed to the planning, conduct and reporting of the work described in the article.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Commissioned; externally peer reviewed.

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