The effect of dapagliflozin across the spectrum of baseline risk: a post-hoc analysis of DAPA-HF

Abstract Background In DAPA-HF, compared to placebo, the sodium-glucose cotransporter 2 (SGLT-2) inhibitor, dapagliflozin, reduced the risk of cardiovascular death or worsening heart failure in patients with heart failure with reduced ejection fraction (HFrEF). The majority of patients in DAPA-HF reported mild functional limitation, however there is significant heterogeneity in prognosis among these patients. Purpose To examine the effect of dapagliflozin compared with placebo across the spectrum of baseline risk in DAPA-HF. Methods The primary composite outcome of DAPA-HF was time-to-first cardiovascular death or worsening heart failure event (hospitalization for heart failure or outpatient visit requiring intravenous therapy). We examined whether the effect of dapagliflozin was modified by baseline risk, as determined by the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) risk score based upon 13 predictive variables giving a potential maximum score of 57. The number needed to treat (NNT) to over a median follow-up of 18.2 months was calculated by applying the overall relative risk reduction in DAPA-HF (26%, 95% CI 15–35) to the proportion of patients with a primary outcome event in the placebo group of each MAGGIC risk score category (defined by quintiles of score). Results The MAGGIC risk score was calculable for 4740 of 4744 patients in DAPA-HF. The median score was 22 (range 3–43). The event rate for the primary outcome was 7.2 per 100 patient-years in the lowest risk score quintile and 25.7 in the highest. A 1-point increase in score was associated with an 8% increase in the risk of a primary outcome event (p