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Efficacy and safety of diuretics in heart failure with preserved ejection fraction: a scoping review
  1. Arushi Singh1,
  2. Anubha Agarwal2,
  3. Q. Eileen Wafford3,
  4. Sanjiv J Shah2,
  5. Mark Huffman4,5,
  6. Sadiya Khan2,5
  1. 1 Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  2. 2 Department of Medicine (Cardiology), Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  3. 3 Galter Health Sciences Library, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  4. 4 George Institute for Global Health, Sydney, New South Wales, Australia
  5. 5 Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  1. Correspondence to Dr Arushi Singh, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; arushi.singh{at}


Objective Diuretics reduce congestion in patients with heart failure with preserved ejection fraction (HFpEF). However, comparison of clinical effects across diuretic classes or combinations of diuretics in patients with HFpEF are not well described. Therefore, we sought to conduct a scoping review to map trial data of diuretic efficacy and safety in patients with HFpEF.

Review methods and results We searched multiple bibliometric databases for published literature and, and hand searched unpublished studies comparing different classes of diuretics to usual care or placebo in patients with HFpEF. We included randomised controlled trials or quasi-experimental studies. Two authors independently screened and extracted key data using a structured form. We identified 13 published studies on diuretics in HFpEF, with 1 evaluating thiazide use, 7 on mineralocorticoid receptor antagonists (MRAs) and 5 on sodium-glucose co-transporter 2 inhibitors (SGLT2i). There remain 17 ongoing trials evaluating loop diuretics (n=1), MRAs (n=5), SGLT2i (n=10) and a polydiuretic (n=1), including 2 well-powered trials of SGLT2i that will be completed in 2021.

Conclusions The limited number of published trials evaluating different classes of diuretics in patients with HFpEF have been generally small and short term. Ongoing and emerging trials of single or combination diuretics with greater power will be useful to better define their safety and efficacy.

Scoping review registration doi:10.18131/g3-dejv-tm77.

  • heart failure
  • diastolic
  • drug interactions

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  • Twitter @ArushiSinghMD, @HFpEF

  • Contributors AS, AA, SJS, MH and SK contributed to the design of the scoping review, the analysis of the results and the writing of the manuscript. QEW developed the study search strategy and performed the initial and updated literature search. AS and AA performed study screening, selection and data extraction.

  • 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 In the past 3 years, MH received funding from the World Heart Federation to serve as its senior programme advisor for the Emerging Leaders programme, which is supported by Boehringer Ingelheim and Novartis with previous support from BUPA and AstraZeneca. MH also receives support from the American Heart Association, Verily, AstraZeneca and American Medical Association for work unrelated to this research. The George Institute for Global Health’s wholly owned enterprise, George Health Enterprises, has received investment funds to develop fixed-dose combination products containing aspirin, statin and blood pressure lowering drugs. AA, MH, SJS and SK plan to submit patents for heart failure polypills, including for heart failure with preserved ejection fraction. SJS has received research grants from the National Institutes of Health (R01 HL107577, R01 HL127028, R01 HL140731, and R01 HL149423), the American Heart Association (#16SFRN28780016), Actelion, AstraZeneca, Corvia, Novartis and Pfizer; and consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Axon Therapeutics, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Cardiora, CVRx, Cytokinetics, Eisai, GSK, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, Shifamed, Tenax and United Therapeutics. SK has received research grants from the American Heart Association (#19TPA34890060) and the National Institutes of Health (P30AG059988; P30DK092939).

  • 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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