Effect of Dapagliflozin, Compared With Placebo, According to Baseline Risk in DAPA-HF

JACC Heart Fail. 2022 Feb;10(2):104-118. doi: 10.1016/j.jchf.2021.09.002. Epub 2022 Jan 12.


Objectives: The authors sought to examine the effect of dapagliflozin across the spectrum of risk in patients enrolled in DAPA-HF.

Background: In the DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin decreased the risk of worsening HF events and cardiovascular death in patients with HF and reduced ejection fraction.

Methods: The MAGGIC (Meta-analysis Global Group in Chronic Heart Failure) and the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) PREDICT-HF (Risk of Events and Death in the Contemporary Treatment of Heart Failure) risk models were used to categorize patients according to risk score quintiles. The authors analyzed rates of the primary composite outcome of a worsening HF event or cardiovascular death, its components, and all-cause mortality according to risk quintile and whether risk modified the effect of dapagliflozin.

Results: The MAGGIC score was available for 4,740 of 4,744 patients in DAPA-HF (median score 22 [IQR: 18-25]). A1-point increase was associated with an 8.2% (95% CI: 6.9%-9.4%) higher relative risk of the primary endpoint (P < 0.001). The benefit of dapagliflozin over placebo for the primary endpoint was similar across the spectrum of MAGGIC risk score (interaction P = 0.71). Applying the overall relative risk reduction (26%) with dapagliflozin added to standard therapy resulted in 7 fewer patients in the highest MAGGIC risk quintile experiencing a primary outcome, compared with 2 in the lowest quintile, per 100 person-years of treatment. The findings with PREDICT-HF were similar, although this model led to better risk discrimination.

Conclusions: The benefits of dapagliflozin were consistent across the broad spectrum of baseline risk in DAPA-HF.

Trial registration: ClinicalTrials.gov NCT03036124.

Keywords: MAGGIC; PREDICT-HF; heart failure; prognostic model; risk score; sodium-glucose cotransporter 2 inhibitor; survival.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds* / therapeutic use
  • Clinical Trials as Topic
  • Glucosides* / therapeutic use
  • Heart Failure* / drug therapy
  • Humans
  • Prospective Studies
  • Risk Assessment


  • Benzhydryl Compounds
  • Glucosides
  • dapagliflozin

Associated data

  • ClinicalTrials.gov/NCT03036124