Quadruple therapy proposed as therapeutic standard for HFrEF

  • Vaduganathan M & al.
  • Lancet
  • 21 May 2020

  • curated by Emily Willingham, PhD
  • Clinical Essentials
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Takeaway

  • These authors analyzed data from 3 randomized controlled trials (RCTs) of individual therapies and argue for a quadruple-therapy approach for treating heart failure (HF) with reduced ejection fraction (rEF).
  • The 4 drug classes are mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, beta-blockers, and sodium/glucose cotransporter 2 inhibitors.

Why this matters

  • These authors say that the combination should be a “new therapeutic standard,” given predicted “aggregate treatment effects” on event-free and overall survival with early use of this comprehensive approach.

Key results

  • Median follow-up among the trials was
  • Compared with conventional therapies (renin-angiotensin inhibitors with beta-blockers), use of the combination yielded reduced risks (HRs; 95% CIs) for:
    • Cardiovascular death/HF hospitalization: 0.38 (0.30-0.47).
    • Cardiovascular death: 0.50 (0.37-0.67).
    • HF hospitalization: 0.32 (0.24-0.43).
    • All-cause mortality: 0.53 (0.40-0.70).
  • They estimated that compared with conventional treatment, the quadruple combination could add 2.7 (95% CI, 2.2-3.3) event-free years for someone age 80 years or 8.3 (6.2-10.7) years for someone age 55 years with HFrEF.

Study design

  • Cross-trial analysis of data from EMPHASIS-HF (n=2737), PARADIGM-HF (n=8399), and DAPA-HF (n=4744) RCTs.
  • The authors projected long-term gains based on assumption of consistent relative treatment effects over time and performed an actuarial analysis.
  • Primary endpoint: composite of cardiovascular death or first HF hospitalization.
  • Funding: None.

Limitations

  • Underlying assumptions could be wrong, especially with potential for nonadherence.
  • Benefits were assumed to be additive, without overlap.
  • Clinical populations in the trials varied.