DAPA-HF Analysis: Dapagliflozin Effective Regardless of Diuretic Use

Alice Jackson, MBChB

After an analysis from ACC.20 found the effects of dapagliflozin seen in the landmark DAPA-HF trial did not vary based on background glucose-lowering therapy, a new study is examining how background diuretic use may have impacted the effects of the SGLT2 inhibitor.

Despite not being a prespecified analysis, results of the new study contribute to clinicians’ current understanding of dapagliflozin and its ability to reduce the risk of heart failure events and cardiovascular death.

“The key finding of the present analyses is that the benefits of dapagliflozin in DAPA-HF were obtained irrespective of use of background diuretic therapy or dose of diuretic therapy,” wrote study investigators.

One of, if not the most, impactful trials in decades, the results of DAPA-HF have been under constant review since they were debuted at ESC Congress 2019. With diuretic therapy common in patients with heart failure, including 84% of patients randomized in DAPA-HF.

With this in mind, a team of clinicians led by Alice Jackson, MBChB, a clinical research fellow at the University of Glasgow, and under the supervision of John McMurray, MD, lead DAPA-HF investigator and professor at the University of Glasgow, performed a post hoc analysis designed to assess the efficacy act and tolerability of dapagliflozin based on background diuretic therapy changes in diuretic therapy during the study.

For the purpose of the analysis, patients were placed into the following subgroups based on diuretic use: no diuretic use, diuretic dose equivalent to less than 40 mg furosemide daily, 40 mg daily, and more than 40 mg daily at baseline. Of note, bumetanide 1 mg, torsemide 20 mg, azosemide 60 mg, and etacrynic acid 100 mg were considered equivalent to 40 mg furosemide.

Of the original 4744 subjects included in DAPA-HF, 4616 were considered analyzable and included in the current analyses. Of these 4616, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on less than 40 mg furosemide daily, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were on more than 40 mg.

The primary end point of the analyses was a composite of cardiovascular death or a worsening heart failure event.

In comparison with patients in these groups receiving placebo, dapagliflozin was associated with 43% (HR, 0.57; 95% CI, 0.36-0.92) reduction in risk of the primary end point in patients receiving no diuretic 17% (HR, 0.83; 95% CI, 0.63-1.10) reduction in risk in patients receiving less than 40 mg daily, and a 23% (HR, 0.77; 95% CI, 0.60-0.99) reduction in risk in patients receiving 40 mg daily, and a 22% (HR, 0.78; 95% CI, 0.68-0.90) reduction in risk among those receiving more than 40 mg daily (P for interaction=.61). When assessing risk in patients taking any diuretic, use of dapagliflozin was associated with a 22% (HR, 0.78; 95% CI, 0.68-0.90) reduction in risk of the primary end point.

Further analysis indicated improvements in symptom and treatment toleration were consistent across all diuretic subgroups. Additionally, diuretic dose did not change in most patients during the study and mean diuretic dose did not differ between the dapagliflozin and placebo arms post-randomization.

This study, “Dapagliflozin and Diuretic Use in Patients with Heart Failure and Reduced Ejection Fraction in DAPA-HF,” was published in Circulation.