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      Patient Characteristics, Clinical Outcomes, and Effect of Dapagliflozin in Relation to Duration of Heart Failure: Is It Ever Too Late to Start a New Therapy?

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          Abstract

          Background

          The impact of heart failure (HF) duration on outcomes and treatment effect is largely unknown. We aim to compare baseline patient characteristics, outcomes and the efficacy and safety of dapagliflozin, in relation to time from diagnosis of HF in DAPA-HF.

          Methods

          HF duration was categorized as ≥2 to ≤12 months, >1-2 years, >2-5 years and >5 years. Outcomes were adjusted for prognostic variables and analyzed using Cox regression. The primary endpoint was the composite of worsening HF or cardiovascular death. Treatment effect was examined within each duration category and by duration threshold.

          Results

          The number of patients in each category was: 1098 (≥2 to ≤12 months), 686 (>1-2 years), 1105 (>2-5 years) and 1855 (>5 years). Longer-duration HF patients were older and more comorbid with worse symptoms. The rate of the primary outcome (per 100 person-years) increased with HF duration: 10.2 (95% CI 8.7-12.0) for ≥2 to ≤12 months, 10.6 (8.7-12.9) >1-2 years, 15.5 (13.6-17.7) >2-5 years and 15.9 (14.5-17.6) for >5 years. Similar trends were seen for all other outcomes. The benefit of dapagliflozin was consistent across HF duration and on threshold analysis. The hazard ratio for the primary outcome ≥2 to ≤12 months was 0.86 (0.63-1.18), >1-2 years 0.95 (0.64-1.42), >2-5 years 0.74 (0.57-0.96) and >5 years 0.64 (0.53-0.78), P-interaction=0.26. The absolute benefit was greatest in longest duration HF, with a number needed-to-treat of 18 for HF >5 years, compared with 28 for ≥2 to ≤12 months.

          Conclusions

          Longer-duration HF patients were older, had more comorbidity and symptoms, and higher rates of worsening HF and death. The benefits of dapagliflozin were consistent across HF duration.

          Registration

          ClinicalTrials.gov; Unique identifier: NCT03036124

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          Author and article information

          Journal
          101479941
          Circ Heart Fail
          Circ Heart Fail
          Circulation. Heart failure
          1941-3289
          1941-3297
          12 March 2021
          01 December 2020
          09 November 2020
          30 March 2021
          : 13
          : 12
          : e007879
          Affiliations
          [1 ]BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
          [2 ]Section of Endocrinology, Yale University School of Medicine, New Haven, CT
          [3 ]Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
          [4 ]Saint Luke’s Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, MO
          [5 ]National University of Cordoba, Cordoba, Argentina
          [6 ]Wroclaw Medical University, Wroclaw, Poland
          [7 ]The TIMI Study Group, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
          [8 ]Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
          [9 ]AstraZeneca, Gothenburg, Sweden
          Author notes
          Address for Correspondence: Professor John J.V. McMurray, British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, United Kingdom. Tel: +44 141 330 3479, Fax: +44 141 330 6955, john.mcmurray@ 123456glasgow.ac.uk
          Article
          PMC7610491 PMC7610491 7610491 ems119217
          10.1161/CIRCHEARTFAILURE.120.007879
          7610491
          33164553
          b61d1946-b834-4405-8baa-3a9e7ab2479d
          History
          Categories
          Article

          dapagliflozin,heart failure,duration
          dapagliflozin, heart failure, duration

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