Su E Yeoh1, Pooja Dewan1, Pardeep S Jhund1, Silvio E Inzucchi2, Lars Køber3, Mikhail N Kosiborod4, Felipe A Martinez5, Piotr Ponikowski6, Marc S Sabatine7, Scott D Solomon8, Olof Bengtsson9, Mikaela Sjöstrand9, Anna Maria Langkilde9, John J V McMurray1. 1. BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (S.E.Y., P.D., P.S.J., J.J.V.M.). 2. Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.). 3. Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark (L.K.). 4. Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City (M.N.K.). 5. National University of Cordoba, Argentina (F.A.M.). 6. Wroclaw Medical University, Poland (P.P.). 7. The TIMI Study Group (M.S.S.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 8. Cardiovascular Division (S.D.S.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 9. AstraZeneca, Gothenburg, Sweden (O.B., M.S., A.M.L.).
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.
RCT Entities:
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.
Authors: John J V McMurray; David L DeMets; Silvio E Inzucchi; Lars Køber; Mikhail N Kosiborod; Anna Maria Langkilde; Felipe A Martinez; Olof Bengtsson; Piotr Ponikowski; Marc S Sabatine; Mikaela Sjöstrand; Scott D Solomon Journal: Eur J Heart Fail Date: 2019-07-15 Impact factor: 15.534
Authors: Stephen J Greene; Adrian F Hernandez; Allison Dunning; Andrew P Ambrosy; Paul W Armstrong; Javed Butler; Lukasz P Cerbin; Adrian Coles; Justin A Ezekowitz; Marco Metra; Randall C Starling; John R Teerlink; Adriaan A Voors; Christopher M O'Connor; Robert J Mentz Journal: J Am Coll Cardiol Date: 2017-06-27 Impact factor: 24.094
Authors: John J V McMurray; David L DeMets; Silvio E Inzucchi; Lars Køber; Mikhail N Kosiborod; Anna M Langkilde; Felipe A Martinez; Olof Bengtsson; Piotr Ponikowski; Marc S Sabatine; Mikaela Sjöstrand; Scott D Solomon Journal: Eur J Heart Fail Date: 2019-03-21 Impact factor: 15.534
Authors: Mikhail N Kosiborod; Pardeep S Jhund; Kieran F Docherty; Mirta Diez; Mark C Petrie; Subodh Verma; Jose C Nicolau; Béla Merkely; Masafumi Kitakaze; David L DeMets; Silvio E Inzucchi; Lars Køber; Felipe A Martinez; Piotr Ponikowski; Marc S Sabatine; Scott D Solomon; Olof Bengtsson; Daniel Lindholm; Anna Niklasson; Mikaela Sjöstrand; Anna Maria Langkilde; John J V McMurray Journal: Circulation Date: 2019-11-17 Impact factor: 29.690
Authors: Su E Yeoh; Pooja Dewan; Akshay S Desai; Scott D Solomon; Jean L Rouleau; Marty Lefkowitz; Adel Rizkala; Karl Swedberg; Michael R Zile; Pardeep S Jhund; Milton Packer; John J V McMurray Journal: ESC Heart Fail Date: 2020-10-19
Authors: Amr Abdin; Stefan D Anker; Javed Butler; Andrew J Stewart Coats; Ingrid Kindermann; Mitja Lainscak; Lars H Lund; Marco Metra; Wilfried Mullens; Giuseppe Rosano; Jonathan Slawik; Jan Wintrich; Michael Böhm Journal: ESC Heart Fail Date: 2021-10-16