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Dapagliflozin reduces first and recurrent HF hospitalizations in DAPA-HF

Prof. Piotr Ponikowski
Wroclaw Medical University
Poland
04 May 2020

The DAPA-HF trial demonstrated a significant reduction in the risk of cardiovascular (CV) death or a first worsening heart failure (HF) event with dapagliflozin vs placebo in patients with HF and a reduced ejection fraction (EF), with or without diabetes. New data from the trial, presented at the American College of Cardiology and World Congress of Cardiology 2020 virtual meeting (ACC.20/WCC), showed that dapagliflozin significantly reduced the risk of both first and recurrent HF hospitalizations in the patients.

In the phase III DAPA-HF trial, 4,744 patients (mean age, 66.2 years in the dapagliflozin group, 66.5 years in the placebo group; 41.8 percent with history of type 2 diabetes mellitus [T2DM]) with New York Heart Association class II–IV HF and an EF of ≤40 percent were randomized (1:1) to receive dapagliflozin (10 mg QD) or placebo, on top of recommended therapy. After a median follow-up of 18.2 months, the primary composite outcome of CV death or a first worsening HF event (ie, unplanned hospitalization or an urgent visit resulting in intravenous therapy for HF) was significantly reduced by 26 percent in the dapagliflozin vs placebo group (hazard ratio [HR], 0.74; 95 percent confidence interval [CI], 0.65 to 0.85; p<0.001). The risk of CV mortality was reduced by 18 percent (HR, 0.82; 95 percent CI, 0.69 to 0.98; p=0.029), while the risk of first HF hospitalization was reduced by 30 percent (HR, 0.70; 95 percent CI, 0.59 to 0.83; p<0.0001). [N Engl J Med 2019;381:1995-2008]

“Patients with HF often experience more than one hospitalization during the course of their disease. Time-to-first event analysis of a composite outcome, such as CV death or HF hospitalization, does not reflect the full burden of HF, and also ignores CV death occurring after a first HF hospitalization,” said DAPA-HF investigator, Professor Piotr Ponikowski of the Wroclaw Medical University, Wroclaw, Poland.

Reductions in first and recurrent HF hospitalizations

A prespecified secondary analysis of DAPA-HF was performed to analyze both first and recurrent HF hospitalizations experienced by patients in the trial. Among the 4,744 patients, 548 (11.55 percent) had ≥1 HF hospitalization. While two thirds (n=380) of the 548 patients experienced one HF hospitalization, about one third (n=168) were hospitalized for HF more than once. A total of 809 first and recurrent HF hospitalizations were reported. [Ponikowski P, et al, ACC/WCC 2020, abstract 412-10]

“About one third of all HF hospitalizations were recurrent events,” said Ponikowski. “Patients who experienced ≥2 HF hospitalizations had more advanced HF, as well as significantly more comorbidities and greater impairment of kidney function.”

“In this secondary analysis, dapagliflozin was shown to reduce both first and recurrent HF hospitalizations,” reported Ponikowski. (Figure 1)

39202r

The relative risk reduction in recurrent events was 25 percent with dapagliflozin vs placebo – an effect consistent with the finding of the time-to-first event analysis. “The effect of dapagliflozin on recurrent HF hospitalizations was even more pronounced, with a relative risk reduction of 29 percent, after accounting for the semi-competing risk of CV death,” said Ponikowski. (Figure 2)

39203r

Furthermore, results on absolute risk reduction (ARR) and number needed to treat (NNT) were more favourable in the recurrent event analysis than in the time-to-first event analysis, Ponikowski noted.

“The recurrent event analysis reflects the real picture of the HF burden,” he said. “In the recurrent event analysis, dapagliflozin demonstrated an ARR in CV death or HF hospitalization of 5.3 per 100 patient-years, with an NNT of 19, and an ARR in HF hospitalization of 3.8 per 100 patient-years, with an NNT of 27. In comparison, the time-to-first event analysis showed an ARR of 3.9 per 100 patient-years with an NNT of 26 for CV death or HF hospitalization, and an ARR of 2.9 per 100 patient-years with an NNT of 35 for HF hospitalization.”

Conclusion

The secondary analysis of the DAPA-HF trial, reported at ACC.20/WCC, showed that a large number of HF patients experienced recurrent HF hospitalizations. These patients had more advanced disease and more comorbidities than those without recurrent HF hospitalizations.

Dapagliflozin demonstrated 25 percent relative risk reductions in both first and recurrent HF hospitalizations. The risk of recurrent HF hospitalizations – a patient-centric endpoint – saw an even greater reduction after accounting for the semi-competing risk of CV death.

These results highlight the importance of collaboration between endocrinologists, cardiologists and primary care physicians in the care of patients with HF, who require multidisciplinary care to reduce the risk of first and recurrent HF hospitalizations.

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