Changes in health-related quality of life and treatment effects in chronic heart failure: a meta-analysis
Introduction
Heart failure (HF) is associated with poor health status, and a high morbidity and mortality [1]. Interventions in HF traditionally have been focused primarily on reducing clinical outcomes, such as mortality and hospitalizations. Over the last decades, patient's health status (studied using validated questionnaires) has been increasingly assessed in randomized controlled trials (RCT) as means of testing the effect of treatment on patient's well-being as an intermediate endpoint [2,3]. In 2019, the Food and Drug Administration (FDA) issued a new guidance proposing patient-centered outcomes, such as functional capacity or health status as acceptable endpoints for clinical trials [4]. A commonly used tool to quantify health status and quality of life in patients with HF is the Kansas City Cardiomyopathy Questionnaire (KCCQ) [5]. According to the FDA guidance, patient-reported outcomes, such as KCCQ-23, are an acceptable primary endpoint to report effectiveness of treatments for HF [4,6]. However, the minimum goal for KCCQ-23 improvement to consider a treatment as effective has not yet been defined; therefore, drug approval based solely on this outcome remains uncertain.
Notwithstanding, despite health status changes being a relevant clinical indicator, it is still not clear how changes in health status are associated with changes in conventional clinical outcomes [7,8]. Therefore, our aim was to conduct a trial-level meta-analysis evaluating whether pharmacologic-induced changes in health status reflect the treatment effects on clinical outcomes in patients with chronic HF.
Section snippets
Study design
We identified completed phase III and IV double-blind RCTs where the impact of pharmacologic treatments for chronic HF on clinical outcomes and patient-reported health status, measured by KCCQ-23 score (for data consistency), was evaluated.
Kansas City Cardiomyopathy Questionnaire-23
KCCQ-23 consists in 23 items that evaluate 7 domains – symptom frequency, symptom burden, symptom stability, physical limitation, social limitation, quality of life, and self-efficacy, yielding 3 summary scores (Clinical Summary Score, Total Symptom Score,
Search results
The search strategy retrieved a total of 372 studies, of which 351 studies were excluded. The reasons for exclusion are described in the flow diagram of the trial selection process depicted in Fig. 1. Sixteen RCTs were included, enrolling a total of 65,608 participants [3,[13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27]]. Five post hoc analysis of these RCTs were included to extract necessary information for the primary and secondary analysis [[28], [29],
Discussion
In this trial-level meta-analysis including over 65,000 patients with HF, we found that treatment-induced changes in KCCQ-23 had a moderate correlation with treatment effects on HF hospitalizations, but the correlation with cardiovascular and all-cause death was weak and statistically non-significant.
KCCQ-23 has been established as a reliable, sensitive patient-centered instrument to quantify health status in patients with HF [33,34]. Besides assessing health status, this tool has been gaining
Conclusion
Treatment-induced changes in KCCQ-23 correlated moderately with treatment effects on HF hospitalizations but were not correlated with treatment effects on cardiovascular and all-cause mortality. KCCQ-23 changes assess patient-centered changes in clinical status and may reflect non-fatal symptomatic changes in the clinical course of HF that may lead to hospitalization. Large outcome trials in chronic HF should continue to assess HF hospitalizations and mortality as robust means to assess
Declaration of Competing Interest
JPF is a consultant for Boehringer-Ingelheim, Astra-Zeneca and Novartis and has received research support from Astra-Zeneca, Novartis and Bayer through his institution, the University of Porto. JB is a consultant for Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, G3 Pharma, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana Medical, and Vifor Pharma. MP has been a consultant
Acknowledgement
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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Cited by (1)
- 1
Drs. Angélico-Gonçalves and Leite contributed equally to this work.
- 2
All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.