Effect of dapagliflozin on anaemia in DAPA-HF

Abstract

Aim: Anaemia is common in heart failure and associated with worse outcomes. We examined the effect of dapagliflozin on correction of anaemia in patients with heart failure (HF) and reduced ejection fraction in DAPA-HF. We also analysed the effect of dapagliflozin on outcomes, according to anaemia status at baseline.

Methods and results: Anaemia was defined at baseline as a haematocrit <39% in men and <36% in women. Resolution of anaemia was defined as two consecutive haematocrit measurements above these thresholds at any time during follow-up. The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized in DAPA-HF, 4691 had a haematocrit available at baseline, of which 1032 were anaemic (22.0%). The rate of the primary outcome was higher in patients with anaemia (16.1 per 100 person-years) compared with those without (12.9 per 100 person-years). Anaemia was corrected in 62.2% of patients in the dapagliflozin group, compared with 41.1% of patients in the placebo group. The effect of dapagliflozin on the primary outcome was consistent in anaemic compared with non-anaemic patients [hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.52-0.88 vs. HR 0.76, 95% CI 0.65-0.89; interaction P = 0.44]. Similar findings were observed for cardiovascular death, HF hospitalization, and all-cause mortality. Patients with resolution of anaemia had better outcomes than those in which anaemia persisted.

Conclusion: Patients with anaemia had worse outcomes in DAPA-HF. Dapagliflozin corrected anaemia more often than placebo and improved outcomes, irrespective of anaemia status at baseline.

Keywords: Anaemia; Clinical trials; Heart failure with reduced ejection fraction; Sodium-glucose co-transporter 2 inhibitor.

Figure 1

Effect of dapagliflozin compared with placebo on cardiovascular outcomes according to presence of anaemia. Kaplan–Meier estimates of the cumulative incidence of: (A) primary composite endpoint [time to first worsening heart failure event, defined as a worsening heart failure event (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or death from cardiovascular causes]; (B) cardiovascular death; (C) worsening heart failure event; (D) all‐cause mortality.

Figure 2

Effect of dapagliflozin compared with placebo on haematocrit according to presence of anaemia. Least square means and 95% confidence intervals were derived from a mixed‐effects model adjusted for baseline values, visit, randomized treatment, and interaction of treatment and visit with a random intercept and slope per patient.