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Original research
Heart failure medication dosage and survival in women and men seen at outpatient clinics
  1. Sophie Heleen Bots1,
  2. N Charlotte Onland-Moret2,
  3. Igor I Tulevski3,
  4. Pim van der Harst4,
  5. Maarten J M Cramer4,
  6. Folkert W Asselbergs4,5,6,
  7. G Aernout Somsen3,
  8. Hester M den Ruijter1
  1. 1Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  3. 3Cardiology Centers of the Netherlands, Amsterdam, The Netherlands
  4. 4Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
  5. 5Institute of Cardiovascular Science, Faculty of Popular Health Sciences, University College London, London, UK
  6. 6Health Data Research UK and Institute of Health Informatics, University College London, London, UK
  1. Correspondence to Prof. dr. ir. Hester M den Ruijter, Utrecht University, Utrecht 3508 TC, The Netherlands; H.M.denRuijter-2{at}umcutrecht.nl

Abstract

Objective Women with heart failure with reduced ejection fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended medication dose. This study investigates prescription practice and its relation with survival of patients with HF in daily care.

Methods Electronic health record data from 13 Dutch outpatient cardiology clinics were extracted for HF receiving at least one guideline-recommended HF medication. Dose changes over consecutive prescriptions were modelled using natural cubic splines. Inverse probability-weighted Cox regression was used to assess the relationship between dose (reference≥50% target dose) and all-cause mortality.

Results The study population comprised 561 women (29% HFrEF (ejection fraction (EF)<40%), 49% heart failure with preserved ejection fraction (EF≥50%); HFpEF and 615 men (47% and 25%, respectively). During a median follow-up of 3.7 years, 252 patients died (48% women; 167 HFrEF, 84 HFpEF). Nine hundred thirty-four patients (46% women) received ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), 795 (48% women) beta blockers and 178 (42% women) mineralocorticoid receptor antagonists (MRAs). In both sexes, the mean target dose across prescriptions was 50% for ACEI/ARBs and beta blockers, and 100% for MRAs. ACEI/ARB dose of <50% was associated with lower mortality in women but not in men with HFrEF. This was not seen in patients with HFpEF. Beta-blocker dose was not associated with all-cause mortality.

Conclusion Patients with HF seen in outpatient cardiology clinics receive half of the guideline-recommended medication dose. Lower ACEI/ARB dose was associated with improved survival in women with HFrEF. These results underscore the importance of (re)defining optimal medical therapy for women with HFrEF.

  • heart failure
  • epidemiology
  • electronic health records

Data availability statement

Data are not available. The Cardiology Centers of the Netherlands database cannot be shared outside the University Medical Center Utrecht's infrastructure because of ethical constraints. The data obtained from Statistics Netherlands are project-specific and cannot be accessed by unregistered researchers.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/heartjnl-2021-319229

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    Data availability statement

    Data are not available. The Cardiology Centers of the Netherlands database cannot be shared outside the University Medical Center Utrecht's infrastructure because of ethical constraints. The data obtained from Statistics Netherlands are project-specific and cannot be accessed by unregistered researchers.

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    Footnotes

    • SHB and NCO-M are joint first authors.

    • Twitter @InnovatieHester

    • Correction notice This article has been corrected since it was first published to correct Table 1. The rows were misaligned in the 'Ejection fraction' section; this has now been amended.

    • Contributors SHB conceived the research question, cleaned the raw data, performed data analyses and wrote the manuscript. NCOM conceived the research question, supported data analysis and critically reviewed the manuscript. IIT and GAS collected the raw data and reviewed the manuscript. PvdH, MJMC and FWA critically reviewed the manuscript. HMdR conceived the research question, obtained funding, supported data analyses and critically reviewed the manuscript. GAS and HMdR are shared last authors.

    • Funding This work was supported by the Dutch Cardiovascular Alliance consortium DCVA IMPRESS (2020B004) and ERC Consolidator grant UCARE (866478).

    • Competing interests GAS and IIT are employed by Cardiology Centers of the Netherlands. FWA is supported by UCL Hospitals NIHR Biomedical Research Centre.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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