Dapagliflozin relieves symptoms, physical limitations in HFpEF patients: PRESERVED-HF trial
USA: Dapagliflozin improves physical limitations and symptoms in patients having heart failure with preserved ejection fraction (HFpEF) within a relatively short period of time, show results of PRESERVED-HF trial. This adds to the recent growing evidence of the benefits of sodium-glucose cotransporter 2 (SGLT2) inhibition in this population.
The findings of the study were presented at the Heart Failure Society of America 2021 meeting in Denver, CO, and subsequently published in the journal Nature Medicine.
According to Mikhail Kosiborod, MD (Saint Luke's Mid America Heart Institute, Kansas City, MO), their trial is the first to demonstrate that the SGLT2 inhibitor dapagliflozin significantly improves symptoms, physical limitations, and 6-minute walking distance in patients with HFpEF
Kosiborod notes that patients with a preserved ejection fraction make up more than half of all heart failure cases. The key goal of management in this group is relieving symptoms and physical limitations. He further points out that "there has been a wide range of therapies that have been tested in this disease condition on these particular outcomes with minimal impact, highlighting a critical unmet clinical need."
SGLT2 inhibitors, including dapagliflozin and empagliflozin were initially developed for the treatment of type 2 diabetes but have also been shown to reduce CV death and worsening heart failure and improve symptoms and physical limitations in HFrEF. Recently, results from the EMPEROR-Preserved trial demonstrated that empagliflozin lowers the risk of CV death/hospitalization for heart failure in HFpEF, but the impact of SGLT2 inhibition on symptoms, physical limitations, and exercise function in this population has remained unclear.
To address this question, PRESERVED-HF, conducted at 26 US centers, was designed. . Investigators randomized 324 patients (mean age of about 70 years; 57% women) with NYHA class II to IV symptoms, an LVEF of 45% or higher, elevated natriuretic peptides, a requirement for diuretic therapy, and at least one of the following enrichment factors: a recent HF hospitalization or urgent HF visit requiring IV diuretics, elevated filling pressure by right or left heart catheterization, or structural heart disease on an echocardiogram.
The average duration of heart failure was about 3 years, with a median LVEF of 60%. 56% of patients had type 2 diabetes and 53% had atrial fibrillation. The median body mass index was 35 kg/m2—much higher than in previous HFpEF trial. More than 40% of patients had NYHA class III or IV symptoms. In addition, the median 6-minute walk distance was 244 meters.
The primary endpoint was the KCCQ clinical summary score, which includes symptoms and physical limitations, at 12 weeks.
Based on the study, the researchers found the following:
- Starting from a "quite low" baseline, patients treated with dapagliflozin saw significant improvements in the clinical summary score, as well as the individual components: total symptom score was 5.8 points better than in the placebo group and the physical limitation score was 5.3 points better. Each of these differences was "clinically meaningful and statistically significant.
- The impact of dapagliflozin was consistent across subgroups, including those defined by the presence of type 2 diabetes, baseline LVEF (divided at the 60% threshold), sex, race, age, and others.
- Patients who received the SGLT2 inhibitors also were significantly more likely to have a clinically meaningful improvement—at least 5 points—in the KCCQ clinical summary score, with a number needed to treat of 9.
- Active treatment led a significant improvement in 6-minute walk distance, with a between-group difference of 20.1 meters, and in the KCCQ overall summary score, with a between-group difference of 4.5 points.
- There were no differences between the trial arms in terms of natriuretic peptides, glycated hemoglobin, or systolic blood pressure, although dapagliflozin resulted in a modest reduction in weight (by 0.72 kg).
- Safety events were balanced between the groups, with no severe hypoglycemic events, lower-limb amputations, or cases of diabetic ketoacidosis in the trial.
To sum up, after 12 weeks of treatment, improvement in the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score was 5.8 points greater in patients treated with dapagliflozin versus placebo.
Kosiborod M. Effects of dapagliflozin on symptoms, function, and quality of life in patients with heart failure and preserved ejection fraction: main results from the PRESERVED-HF trial. Presented at: HFSA 2021. September 12, 2021. Denver, CO.