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What would it mean for your HFrEF patients to feel better?

PARADIGM-HF evaluated patients' overall quality of life (QoL) using the KCCQ-23, which includes these domains1,2:

  • Physical limitation

  • Symptom frequency

  • Symptom burden

  • Symptom stability

  • Self-efficacy

  • Social limitation

  • QoL

Each domain is scored on a scale of 0-100; higher scores indicate better health status.

The KCCQ-23 Clinical Summary score (CS) represents the average of the symptom (frequency and burden) and physical limitation domains.1,2 

Analysis included all patients with at least 1 KCCQ data up to month 8. For patients who died, the worst score (0) was imputed for the CS at all subsequent scheduled visits.

KCCQ-23 results

Change in the KCCQ-23 CS from baseline to 8 months was a prespecified secondary outcome in PARADIGM-HF.1,3

Mean change in KCCQ-23 CS at 8-month, double-blind period: ENTRESTO -2.99 (n=4187), enalapril -4.63 (n=4212). Clinically meaningful difference established as 5 points.3 

PARADIGM-HF: KCCQ-23 analysis limitations2

  • Baseline KCCQ-23 CS in the overall PARADIGM-HF population was assessed at randomization. This may have resulted in higher baseline scores due to treatment during the run-in phase. Limited data exist assessing clinical meaningfulness of change scores in patients with relatively good baseline perceptions of HRQoL

  • Statistical analysis suggests that the difference between ENTRESTO and enalapril treatment arms may have been driven in part by the treatment effect on HF hospitalizations

KCCQ-23 tool limitations1,2

  • 2-week recall period

  • Missing scores in physical limitation domain due to conditions other than HF

*In PARAGON-HF, defined as LVEF ≥45% with structural heart disease (LAE or LVH); median LVEF was 57%. LVEF is a variable measure and the normal range can vary.4

Important Safety Information

BOXED WARNING: FETAL TOXICITY

  • When pregnancy is detected, discontinue ENTRESTO as soon as possible
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus

ENTRESTO is contraindicated in patients with hypersensitivity to any component...

Indication

ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal.

LVEF is a variable measure, so use clinical judgment in deciding whom to treat.

Click or scroll to see IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING AND INDICATION

Definitions
ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; HRQoL, health-related quality of life; KCCQ-23, Kansas City Cardiomyopathy Questionnaire-23; NYHA, New York Heart Association.

References
1. Spertus JA, Jones PG. Development and validation of a short version of the Kansas City Cardiomyopathy Questionnaire. Circ Cardiovasc Qual Outcomes. 2015;8(5):469-476. doi:10.1161/CIRCOUTCOMES.115.001958
2. Lewis EF, Claggett BL, McMurray JJV, et al. Health-related quality of life outcomes in PARADIGM-HF. Circ Heart Fail. 2017;10(8):e003430. doi:10.1161/CIRCHEARTFAILURE.116.003430
3. McMurray JJV, Packer M, Desai AS, et al; for the PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi:10.1056/NEJMoa1409077
4. ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.