Patients taking ENTRESTO experienced less decline than those taking enalapril†
PARADIGM-HF utilized the Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23), a measurement of health-related quality of life (HRQoL) assessing these domains: physical limitation, symptom frequency, symptom burden, symptom stability, self-efficacy, social limitation, and quality of life. Each domain is scored on a scale of 0-100; higher scores indicate better health status1,3
The KCCQ-23 Clinical Summary score (CS) represents the average of the symptom (frequency and burden) and physical limitation domains1,3
The KCCQ-23 Overall Summary score (OS) represents the average of the CS as well as the quality of life and social limitation domains. PARADIGM-HF KCCQ-23 change from baseline to Month 8 in OS was -2.35 for ENTRESTO and -4.27 for enalapril1,3
†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.
PARADIGM-HF: KCCQ-23 ANALYSIS & KCCQ-23 TOOL LIMITATIONS
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 heart failure hospitalizations
KCCQ-23 tool limitations3,4
Two week recall period
Missing scores in physical limitation domain due to conditions other than heart failure
PARADIGM-HF PRIMARY END POINT
PARADIGM-HF was a multinational, randomized, double-blind trial comparing ENTRESTO to enalapril in 8442 symptomatic (NYHA Class Il-IV) adult HFrEF patients (LVEF ≤40%). After discontinuing their existing ACEi or ARB therapy, patients entered sequential single-blind run-in periods during which they received enalapril, followed by ENTRESTO. Patients who successfully completed the run-in periods were then randomized to receive either ENTRESTO 97/103 mg (n=4209) twice daily or enalapril 10 mg (n=4233) twice daily. The median follow-up duration was 27 months, and patients were treated for up to 4.3 years. For the primary end point, composite of CV death or first heart failure hospitalization, ENTRESTO was superior to enalapril (P<0.0001).
LVEF=left ventricular ejection fraction;
NYHA=New York Heart Association.
ENTRESTO patients had improved HRQoL scores3,5
CHAMP-HF: Patients taking ENTRESTO reported less physical and social limitation, and improved QoL
‡A change of 5 points was considered a minimal clinically important difference. §Changes between pre- and postmatch scores shown over a median of 57 days (32-104).
The CHAnge the Management of Patients with Heart Failure (CHAMP-HF) registry evaluated the real-world care and outcomes of 5026 patients with chronic HFrEF
CHAMP-HF utilized the KCCQ-12, a shortened version of the KCCQ-23, which assesses the following domains: physical limitation, symptom frequency, social limitation, and quality of life
The KCCQ-12 Overall Summary Score represents the average of all 4 domains. A Clinical Summary Score is not a component of the KCCQ-12
CHAMP-HF REGISTRY DESIGN & KCCQ-12 ANALYSIS
CHAMP-HF Registry Design & KCCQ-12 analysis5,6
CHAnge the Management of Patients with Heart Failure (CHAMP-HF) was a multicenter, observational, prospective registry study that evaluated care and outcomes of 5026 adult heart failure patients with reduced EF (LVEF ≤40%) on at least 1 oral heart failure pharmacotherapy across practices in the United States. Patients were followed up to 24 months or until death/study withdrawal. CHAMP-HF utilized KCCQ-12, a shortened version of the KCCQ-23, which assesses the following domains: physical limitation, symptom frequency, social limitation, and quality of life. The KCCQ-12 Overall Summary Score (OS) represents the average of all 4 domains. A Clinical Summary Score is not a component of the KCCQ-12
This analysis cohort included 1524 patients–508 who started ENTRESTO after enrollment and 1016 who did not. Patients were propensity matched in a 1:2 ratio based on a time-dependent propensity score, most recent KCCQ-12 OS, and ACEi/ARB status.
The primary outcome was change in KCCQ-12 OS from the last pre-match assessment to the first post-match assessment (≥2 weeks after initiation, for ENTRESTO patients).
ACEi=angiotensin-converting enzyme inhibitor;
ARB=angiotensin II receptor blocker.
CHAMP-HF: KCCQ-12 ANALYSIS LIMITATIONS
CHAMP-HF: KCCQ-12 analysis limitations5
Observational registry design susceptible to bias due to unmeasured confounding. Role of placebo effect due to open-label ENTRESTO use cannot be excluded
Patients who started ENTRESTO may be different from patients who did not
Findings may not be generalizable throughout the United States or to other countries
KCCQ-23 tool limitations also apply to the KCCQ-12
HFrEF=heart failure with reduced ejection fraction.
*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.7