Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction: A Prespecified Analysis of DAPA-HF - PubMed (original) (raw)

Randomized Controlled Trial

. 2020 Oct 27;142(17):1623-1632.

doi: 10.1161/CIRCULATIONAHA.120.047480. Epub 2020 Sep 4.

Pardeep S Jhund # 1, Inder Anand 2, Olof Bengtsson 3, Michael Böhm 4, Rudolf A de Boer 5, David L DeMets 6, Akshay S Desai 7, Jaroslaw Drozdz 8, Jonathan Howlett 9, Silvio E Inzucchi 10, Per Johanson 3, Tzvetana Katova 11, Lars Køber 12, Mikhail N Kosiborod 13 14, Anna Maria Langkilde 3, Daniel Lindholm 3, Felipe A Martinez 15, Béla Merkely 16, Jose C Nicolau 17, Eileen O'Meara 18, Piotr Ponikowski 19, Marc S Sabatine 20, Mikaela Sjöstrand 3, Scott D Solomon 7, Sergey Tereshchenko 21, Subodh Verma 22, John J V McMurray 1

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Randomized Controlled Trial

Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction: A Prespecified Analysis of DAPA-HF

Kieran F Docherty et al. Circulation. 2020.

Abstract

Background: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), dapagliflozin, added to guideline-recommended therapies, reduced the risk of mortality and heart failure (HF) hospitalization. We examined the frequency and significance of episodes of outpatient HF worsening, requiring the augmentation of oral therapy, and the effects of dapagliflozin on these additional events.

Methods: Patients in New York Heart Association functional class II to IV, with a left ventricular ejection fraction ≤40% and elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide), were eligible. The primary outcome was the composite of an episode of worsening HF (HF hospitalization or an urgent HF visit requiring intravenous therapy) or cardiovascular death, whichever occurred first. An additional prespecified exploratory outcome was the primary outcome plus worsening HF symptoms/signs leading to the initiation of new, or the augmentation of existing, oral treatment.

Results: Overall, 36% more patients experienced the expanded, in comparison with the primary, composite outcome. In the placebo group, 684 of 2371 (28.8%) patients and, in the dapagliflozin group, 527 of 2373 (22.2%) participants experienced the expanded outcome (hazard ratio, 0.73 [95% CI, 0.65-0.82]; P<0.0001). Each component of the composite was reduced significantly by dapagliflozin. Over the median follow-up of 18.2 months, the number of patients needed to treat with dapagliflozin to prevent 1 experiencing an episode of fatal or nonfatal worsening was 16. Among the 4744 randomly assigned patients, the first episode of worsening was outpatient augmentation of treatment in 407 participants (8.6%), an urgent HF visit with intravenous therapy in 20 (0.4%), HF hospitalization in 489 (10.3%), and cardiovascular death in 295 (6.2%). The adjusted risk of death from any cause (in comparison with no event) after an outpatient worsening was hazard ratio, 2.67 (95% CI, 2.03-3.52); after an urgent HF visit, the adjusted risk of death was hazard ratio, 3.00 (95% CI, 1.39-6.48); and after a HF hospitalization, the adjusted risk of death was hazard ratio, 6.21 (95% CI, 5.07-7.62).

Conclusion: In DAPA-HF, outpatient episodes of HF worsening were common, were of prognostic importance, and were reduced by dapagliflozin. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03036124.

Keywords: heart failure; hospitalization; sodium-glucose transporter 2 inhibitors; therapy; treatment outcome.

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Figures

Figure 1.

Figure 1.

Kaplan-Meier curves for the expanded composite outcome of time to first cardiovascular death, hospitalization for heart failure, urgent heart failure visit, or outpatient intensification of heart failure therapy, according to treatment group. Hazard ratios (HR) and 95% CIs were estimated with the use of Cox regression models, stratified according to diabetes status, with a history of hospitalization for heart failure and treatment-group assignment as explanatory variables.

Figure 2.

Figure 2.

Effect of dapagliflozin versus placebo on manifestations of worsening heart failure. Hazard ratios and 95% CIs were estimated with the use of Cox regression models, stratified according to diabetes status, with a history of hospitalization for heart failure and treatment-group assignment as explanatory variables. CV indicates cardiovascular; and HF, heart failure.

Figure 3.

Figure 3.

Rate and risk of all-cause mortality after a first nonfatal heart failure worsening event. The risk of each death from any cause relative to patient not experiencing an event after a first nonfatal heart failure worsening event is calculated by using Cox regression models with the event entered in the model as a time-updated covariate. HF indicates heart failure; and HR, hazard ratio.

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