Effects of low-dose dapagliflozin on heart failure–related outcomes in patients with heart failure and type 2 diabetes: a subanalysis of the dapper study

Background The efficacy of sodium–glucose cotransporter 2 inhibitors in heart failure (HF) has been well established. Dapagliflozin 10 mg has been shown to improve clinical outcomes in HF in DAPA-HF and DELIVER; however, evidence supporting low-dose dapagliflozin in HF remains limited. Purpose This post hoc analysis of the DAPPER study aims to assess the effect of dapagliflozin 5 mg on HF-related events in patients with type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF). Methods The DAPPER study was a multicenter, randomized, open-label trial that enrolled patients with T2DM and CHF, randomly assigned to dapagliflozin (n = 146) or control (n = 148) and followed for 96 weeks. This subanalysis included 128 patients who received dapagliflozin 5 mg throughout the study and 138 control patients. The primary endpoint was a hierarchical composite consisting of cardiovascular death, HF hospitalization frequency, time to first HF hospitalization and escalation of HF medical therapy, assessed using the win ratio approach. Results The primary win ratio analysis favored dapagliflozin, which was superior in 19.34% of paired comparisons compared with 5.04% for control, yielding a win ratio of 3.84 (95% CI, 1.92–10.17; permutation P < 0.001). Dapagliflozin significantly reduced the frequency of HF hospitalizations (rate ratio, 0.20; 95% CI, 0.05–0.85; P = 0.03) and escalation of HF medical therapy (hazard ratio, 0.25; 95% CI, 0.11–0.58; P = 0.001). Conclusions In patients with T2DM and CHF, dapagliflozin 5 mg was associated with clinically meaningful improvements in hierarchical HF-related outcomes compared with control.