Dapagliflozin reduces HF hospitalization in high-risk T2D patients regardless of EF

Takeaway

• Dapagliflozin (Farxiga) reduces hospitalization for heart failure (HHF) among patients with type 2 diabetes (T2D) and high cardiovascular risk, regardless of ejection fraction (EF) status.

Why this matters

• T2D is a well-established HF risk factor.

Study design

• Among 17,160 DECLARE-TIMI 58 trial participants, 3.9% had EF<45% (HF with reduced EF [HFrEF]), 7.7% had HF history without reduced EF, and 88.4% had no HF history or documented reduced EF.   
• Funding:AstraZeneca.

Key results

• HR for dapagliflozin vs placebo for cardiovascular death/HFF overall:
  • 0.83 (P=.005).
• Dapagliflozin reduced CV death/HHF risk (HRs, 95% CIs):
  • In patients with HFrEF: 0.62 (0.45-0.86); 
  • Less so without HFrEF: 0.88 (0.76-1.02; P_interaction=.046).
• Heterogeneity driven by dapagliflozin reducing cardiovascular death in patients (HRs; 95% CIs):
  • With HFrEF: 0.55 (0.34-0.90; P=.02);
  • But not without HFrEF: 1.08 (0.89-1.31; P_interaction=.012).
• Dapagliflozin significantly reduced all-cause mortality (HRs; 95% CIs):
  • With HFrEF: 0.59 (0.40-0.88; P=.01); 
  • But not without: 0.97 (P_interaction=.016).
• Dapagliflozin reduced HHF regardless of EF (HR; 95% CIs):
  • With HFrEF: 0.64 (0.43-0.95); 
  • Without HFrEF: 0.76 (0.62-0.92; P_interaction=.45).
• No heterogeneity between patients with HF without known HFrEF vs with no HF history (HRs; 95% CIs):
  • 0.72 (0.50-1.04) vs
  • 0.77 (0.60-0.97), respectively. 

Limitations

• Trial not designed specifically to assess HF patients.
• No specified preenrollment time window for EF determination.