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. 2021 May 18;143(20):1962-1972.
doi: 10.1161/CIRCULATIONAHA.121.053659. Epub 2021 Apr 9.

Dapagliflozin and Recurrent Heart Failure Hospitalizations in Heart Failure With Reduced Ejection Fraction: An Analysis of DAPA-HF

Pardeep S Jhund #  1 , Piotr Ponikowski #  2 , Kieran F Docherty  1 , Samvel B Gasparyan  3 , Michael Böhm  4 , Chern-En Chiang  5 , Akshay S Desai  6 , Jonathon Howlett  7 , Masafumi Kitakaze  8 , Mark C Petrie  1 , Subodh Verma  9 , Olof Bengtsson  3 , Anna-Maria Langkilde  3 , Mikaela Sjöstrand  3 , Silvio E Inzucchi  10 , Lars Køber  11 , Mikhail N Kosiborod  12   13 , Felipe A Martinez  14 , Marc S Sabatine  15 , Scott D Solomon  6 , John J V McMurray  1
Affiliations

Dapagliflozin and Recurrent Heart Failure Hospitalizations in Heart Failure With Reduced Ejection Fraction: An Analysis of DAPA-HF

Pardeep S Jhund et al. Circulation. .

Abstract

Background: Patients with heart failure (HF) and reduced ejection fraction will experience multiple hospitalizations for heart failure during the course of their disease. We assessed the efficacy of dapagliflozin on reducing the rate of total (ie, first and repeat) hospitalizations for heart failure in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure).

Methods: The total number of HF hospitalizations and cardiovascular deaths was examined by using the proportional-rates approach of Lei-Wei-Yang-Ying and a joint frailty model for each of recurrent HF hospitalizations and time to cardiovascular death. Variables associated with the risk of recurrent hospitalizations were explored in a multivariable Lei-Wei-Yang-Ying model.

Results: Of 2371 participants randomly assigned to placebo, 318 experienced 469 hospitalizations for HF; of 2373 assigned to dapagliflozin, 230 patients experienced 340 admissions. In a multivariable model, factors associated with a higher risk of recurrent HF hospitalizations included higher heart rate, higher N-terminal pro-B-type natriuretic peptide, and New York Heart Association class. In the Lei-Wei-Yang-Ying model, the rate ratio for the effect of dapagliflozin on recurrent HF hospitalizations or cardiovascular death was 0.75 (95% CI, 0.65-0.88), P=0.0002. In the joint frailty model, the rate ratio for total HF hospitalizations was 0.71 (95% CI, 0.61-0.82), P<0.0001, whereas, for cardiovascular death, the hazard ratio was 0.81 (95% CI, 0.67-0.98), P=0.0282.

Conclusions: Dapagliflozin reduced the risk of total (first and repeat) HF hospitalizations and cardiovascular death. Time-to-first event analysis underestimated the benefit of dapagliflozin in HF and reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

Keywords: 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; heart failure; recurrence; sodium-glucose transporter 2 inhibitors.

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Figures

Figure 1.
Figure 1.
Number of extra cardiovascular (CV) deaths and heart failure (HF) hospitalizations in a recurrent-events analysis compared with time-to-first event analysis by treatment group.
Figure 2.
Figure 2.
Number of patients with ≥1 hospitalization in the dapagliflozin and placebo groups. HF indicates heart failure.
Figure 3.
Figure 3.
Variables associated with cardiovascular death or recurrent HF hospitalizations in a multivariable model using the Lin-Wei-Yang-Ying method to model recurrent events. eGFR indicates estimated glomerular filtration rate; HF, heart failure; LVEF, left ventricular ejection fraction; NTproBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; and SBP, systolic blood pressure.
Figure 4.
Figure 4.
Cumulative incidence of total heart failure hospitalizations and cardiovascular death. py indicates person-years.
Figure 5.
Figure 5.
Effect of dapagliflozin on cardiovascular death or HF hospitalization using a time-to-first event Cox model, recurrent HF hospitalizations or cardiovascular death using the LWYY method and joint frailty model. CV indicates cardiovascular; HF, heart failure; and LWYY, Lin-Wei-Yang-Ying.
Figure 6.
Figure 6.
Effect of dapagliflozin compared with placebo on recurrent heart failure hospitalizations or cardiovascular death by subgroups as modeled by the Lin-Wei-Yang-Ying method. AF indicates atrial fibrillation; BMI, body mass index; eGFR, estimated glomerular filtration rate; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonist; NTproBNP, N-terminal pro-B-type natriuretic peptide; and NYHA, New York Heart Association.
See this image and copyright information in PMC

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