PARADIGM-HF: Patients taking ENTRESTO® felt better than those taking enalapril1
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 status1,2
The KCCQ-23 Clinical Summary Score (CS) represents the average of the symptom (frequency and burden) and physical limitation domains1,2
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 enalapril1,2
*Clinically meaningful difference established as 5 points.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.
Recall period for KCCQ is 2 weeks, rather than daily
Patients who do not perform activities because of conditions other than their HF will have missing scores for the physical limitation domain
Additional limitations of KCCQ-23 analysis as utilized in PARADIGM-HF3
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
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 systolic HF patients (LVEF ≤40%). After discontinuing their existing ACEi or ARB therapy, patients entered sequential single-blind run-in periods during which they received enalapril 10 mg twice daily, followed by ENTRESTO 100 mg (49/51 mg) twice daily, increasing to 200 mg (97/103 mg) twice daily. Patients who successfully completed the run-in periods were then randomized to receive either ENTRESTO 200 mg (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 HF hospitalization, ENTRESTO was superior to enalapril (P<0.0001).
ENTRESTO patients had improved HRQoL scores2,5
CHAMP-HF registry: Patients taking ENTRESTO experienced improvement in HRQoL overall summary score compared to those not taking ENTRESTO
‡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 KCCQ STUDY DESIGN
CHAMP-HF KCCQ analysis study design5,6
The CHAnge the Management of Patients with Heart Failure (CHAMP-HF) registry evaluated the care and outcomes of patients with chronic HFrEF by assessing real-world treatment patterns, as well as the reasons for and barriers to medication treatment changes. CHAMP-HF enrolled 5026 patients with HFrEF, and patients were followed for a maximum duration of 24 months, or until death or study withdrawal. CHAMP-HF utilized Kansas City Cardiomyopathy Questionnaire 12-item questionnaire (KCCQ-12) to assess patient-reported HF-related QOL.
CHAMP-HF was a multicenter, observational, prospective, nonrandomized study designed to capture the care and outcomes of patients with HFrEF across outpatient practices in the United States. Eligibility criteria included adults with a diagnosis of chronic HFrEF (left ventricular ejection fraction ≤40%) and use of at least 1 oral pharmacotherapy as part of routine outpatient management for heart failure.
Patients were classified as:
New ARNI starts = patients who begin ARNI
therapy at or after enrollment
No-ARNI patients = patients who do not
begin ARNI therapy
The KCCQ analysis cohort included 1524 patients, 508 who started an ARNI and 1016 who did not, matched in a 1:2 ratio.
Among the ARNI patients, 267 were on an ACEi/ARB in the 2 weeks prior to the ARNI (534 matched no ARNI) and 241 were not on an ACEi/ARB at the time of ARNI start (482 matched no-ARNI)
The primary outcome of the KCCQ analysis was the overall KCCQ score, from the first assessment that occurs at least 2 weeks after the ARNI initiation date, or that occurs on or after the match date for no ARNI patients.
CHAMP-HF KCCQ STUDY LIMITATIONS
Limitations of the KCCQ-23 also apply
Additional limitations of KCCQ-12 analysis as utilized in CHAMP-HF
CHAMP-HF was an observational registry and is thereby susceptible to bias as a result of unmeasured confounding. The role of placebo effect due to open-label ARNI use cannot be excluded
Patients who start an ARNI may be different from patients who do not
Findings may not be generalizable throughout the United States or to other countries
Results only apply to outpatients with HFrEF