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?

Circ Heart Fail. 2020 Dec;13(12):e007879. doi: 10.1161/CIRCHEARTFAILURE.120.007879. Epub 2020 Nov 9.

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 trial (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure).

Methods: HF duration was categorized as ≥2 to ≤12 months, >1 to 2 years, >2 to 5 years, and >5 years. Outcomes were adjusted for prognostic variables and analyzed using Cox regression. The primary end point 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-≤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 to 2 years, 15.5 (13.6-17.7) >2 to 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 to 2 years 0.95 (0.64-1.42), >2 to 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: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

Keywords: comorbidity; dapagliflozin; heart failure; patients; prognosis.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzhydryl Compounds / therapeutic use*
  • Biomarkers / blood
  • Comorbidity
  • Diabetes Complications / drug therapy
  • Double-Blind Method
  • Female
  • Glucosides / therapeutic use*
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Time Factors

Substances

  • Benzhydryl Compounds
  • Biomarkers
  • Glucosides
  • Sodium-Glucose Transporter 2 Inhibitors
  • dapagliflozin

Associated data

  • ClinicalTrials.gov/NCT03036124