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The effect of down-titration and discontinuation of heart failure pharmacotherapy in older people: a systematic review and meta-analysis
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  • Mai Duong,
  • Danijela Gnjidic,
  • Andrew McLachlan,
  • Mitchell Redston,
  • Parag Goyal ,
  • Stephanie Mathieson,
  • Sarah Hilmer
Mai Duong
The University of Sydney Faculty of Medicine and Health

Corresponding Author:mai.duong@sydney.edu.au

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Danijela Gnjidic
3Charles Perkins Centre, University of Sydney
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Andrew McLachlan
The University of Sydney
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Mitchell Redston
University of New South Wales Faculty of Medicine
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Parag Goyal
Weill Cornell Medicine
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Stephanie Mathieson
The University of Sydney Faculty of Medicine and Health
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Sarah Hilmer
Royal North Shore Hospital and University of Sydney
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Abstract

Aim: To investigate if interventions to discontinue or down-titrate heart failure (HF)-pharmacotherapy are feasible and associated with risks in older people. Methods: A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Electronic databases were searched from inception to March 8th 2023. Randomised controlled trials (RCTs) and observational studies included people with HF, aged >50 years and who discontinued or down-titrated HF-pharmacotherapy. Outcomes were feasibility (whether discontinuation or down-titration of HF-pharmacotherapy was sustained at follow-up) and associated risks (mortality, hospitalisation, adverse drug withdrawal effects [ADWE]). Random-effects meta-analysis was performed when heterogeneity was not substantial (Higgins I2<70%). Sub-analysis by frailty status was conducted. Results: Six RCTs (536-participants) and 27 observational studies (810,499-participants) across six therapeutic classes were included, for 3-260 weeks follow-up. RCTs were conducted in patients presenting with stable HF. Down-titrating a renin-angiotensin system inhibitor (RASI) in patients with chronic kidney disease was 76% likely than continuation (Risk Ratio [RR] 1.76, 95%CI 1.14-2.73), with no difference in mortality (RR 0.64, 95%CI 0.30-1.64). Discontinuation of beta-blockers were feasible compared to continuation in preserved ejection fraction (RR 1.00, 95%CI 0.68-1.47). Participants were 25% likely to re-initiate discontinued diuretics (RR 0.75, 95%CI 0.66-0.86). Digoxin discontinuation was associated with 5.5-fold risk of hospitalisation compared to continuation. Worsening HF was the commonest ADWE. One observational study measured frailty but did not report outcomes by frailty status. Conclusions: The appropriateness and associated risks of down-titrating or discontinuing HF-pharmacotherapy in people aged >75 years is uncertain. Evaluation of outcomes by frailty status necessitates investigation.
27 Mar 2024Submitted to British Journal of Clinical Pharmacology
01 Apr 2024Submission Checks Completed
01 Apr 2024Assigned to Editor
01 Apr 2024Review(s) Completed, Editorial Evaluation Pending
11 Jul 2024Editorial Decision: Revise Major
21 Jul 20241st Revision Received
26 Jul 2024Submission Checks Completed
26 Jul 2024Assigned to Editor
26 Jul 2024Review(s) Completed, Editorial Evaluation Pending
01 Aug 2024Editorial Decision: Accept