Beneficial effect of SGLT2i in HFrEF independent of use of diuretic therapy

Dapagliflozin and diuretic use in patients with heart failure and reduced ejection fraction in DAPA-HF

HFA Discoveries 2020 webinar presented by dr. Alice Jackson (Glasgow,GB)

Introduction and methods

The DAPA-HF trial showed that SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure (HF) or CV death in patients with HFrEF. Effects of SGLT2 inhibition include natriuresis, glycosuria and water excretion. In DAPA-HF, 84% of patients were treated with conventional diuretics at baseline. However, little is known about the effects of adding a SGLT2 inhibitor in patients with HFrEF who are already on conventional diuretic therapy.

This analysis of patients in the DAPA-HF trial investigated efficacy and safety outcomes according to diuretic category. A total of 4616 patients from the DAPA-HF trial were categorized into 4 groups according to furosemide-equivalent daily doses of loop diuretic: no diuretic (n=736), <40 mg (n=1311), 40 mg (n=1365) and >40 mg (n=1204). Patients on a non-loop diuretic only were included in the <40 mg group.

Main results

• Mean furosemide-equivalent dose was similar at baseline in placebo and dapagliflozin groups at baseline (60.8±96.8 mg in the placebo group, 59.0±94.9 mg in the dapagliflozin), and rose slightly and at a similar rate over time in both groups.
• Most patients remained on the same diuretic dose as on baseline (83% in the placebo group and 84% of patients in the dapagliflozin group at 6 months, and 77% in both groups at 12 months). A small proportion of patients had their dose of diuretics decreased. This happened slightly more frequently in the dapagliflozin group than in the placebo group, but with only a 3% and 4% difference between treatment groups at 6 and 12 months, respectively.
• Risks of the primary composite outcome in DAPA-HF (worsening heart failure or CV death), and individual outcomes of worsening HF event, CV death and all-cause death were reduced by dapagliflozin compared with placebo in all patients whether treated or not treated with a diuretic and also irrespective of diuretic dose. Tests for interactions were non-significant, both for patients on any dose of diuretic and across dose categories. This indicates that the effect of dapagliflozin was not modified by diuretic use or diuretic dose.
• An early and sustained increase in hematocrit was observed in the dapagliflozin group compared to the placebo group, irrespective of diuretic dose or change in dose. Changes in creatinine and systolic blood pressure were similar in dapagliflozin and placebo groups across the diuretic dose categories.
• Amongst patients on a diuretic, there was a tendency towards more volume depletion in patients on dapagliflozin, compared with those on placebo (P for interaction=0.012). This did not influence the frequency of renal adverse events (P for interaction=0.12) nor of discontinuation due to adverse events (P for interaction = 0.31) between treatment groups.

Conclusions

This analysis showed that most patients did not change diuretic dose during follow-up in the DAPA-HF trial. Benefits of dapagliflozin in reducing the risk of the primary composite endpoint, its components and all-cause death persisted irrespective of use of diuretics or diuretic dose. Renal adverse events and discontinuation due to adverse events were not more frequent in patients receiving dapagliflozin, compared to patients on placebo. Treatment with dapagliflozin led to a sustained elevation of hematocrit, irrespective of use of diuretic, dose or change of dose.

-Our reporting is based on the information provided by the HFA Discoveries webinar -