Physicians' Academy for Cardiovascular Education

No effect of SGLT2i on six minute walk distance in HFrEF and HFpEF

News - July 6, 2021

Effect of Dapagliflozin vs Placebo on Symptoms and Six-Minute Walk Distance in Patients with Heart Failure

Presented at ESC Heart Failure 2021 by Prof. John McMurray, MD (Glasgow, UK)

Introduction and methods

The effect of SGLT2i on walking distance in patients with HF is uncertain. The DETERMINE trials assessed the effect of dapagliflozin on self-reported symptoms, physical limitations and walking distance in patients with HFrEF (DETERMINE-Reduced) or HFpEF (DETERMINE-Preserved).

DETERMINE-Reduced randomized 313 patients with LVEF ≤40%, NT-proBNP ≥400 pg/ml (≥300 pg/ml if hospitalized for HF in the past 12 months, ≥800 pg/ml if AF), and eGFR ≥25 ml/min/1.73m². DETERMINE-Preserved randomized 504 patients with LVEF >40% and evidence of structural heart disease, NT-proBNP ≥250 pg/ml (≥500 pg/ml if AF), and eGFR ≥25 ml/min/1.73m². Patients in both trials needed to be on stable treatment and had a stable 6 minute walking distance (6MWD) between 100 and 425 meters during the run-in phase (≤15% difference in 6MWD required between visits). In both DETERMINE trials, patients were randomized (1:1) to receive either dapagliflozin (10 mg once daily) or placebo for 16 weeks. The primary outcome consisted of three components: 1) change in patient-reported HF symptoms (change from baseline in the KCCQ-TSS at week 16); 2) change in patient-reported physical limitation (change from baseline in the KCCQ-PLS at week 16); and 3) change in 6MWD from baseline to week 16.

Main results




Dapagliflozin, compared to placebo, significantly improved HF symptoms (measured by KCCQ-TSS) in patients with HFrEF, but did not improve physical limitations (measured by KCCQ-PLS) or 6 minute walk distance. No significant improvements with dapagliflozin compared to placebo were seen in any of these outcomes in patients with HFpEF.


Prof. McMurray mentioned that he was surprised that SGLT2i have no effect on 6MWD, despite the clear benefits of SGLT2i in patients with HFrEF on symptoms, HF hospitalization and mortality. He also revered to the EMPERIAL-Reduced trial that also showed no effect of SGLT2i on 6MWD. These results lead to the question whether 6MWD it is a good measure to evaluate the effect of a therapy on HF. The discussant Prof. Massimo Piepoli, MD (Piacenza, Italy) agreed that there is a concern whether 6MWD is a good measure to assess limitations in exercise capacity. As an alternative he mentioned the cardiopulmonary exercise test. However, some patients are not eligible for this test, especially older and frail patients.

-Our reporting is based on the information provided at the ESC Heart Failure 2021 congress-

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