Elsevier

International Journal of Cardiology

Volume 386, 1 September 2023, Pages 65-73
International Journal of Cardiology

Changes in health-related quality of life and treatment effects in chronic heart failure: a meta-analysis

https://doi.org/10.1016/j.ijcard.2023.05.032Get rights and content

Highlights

  • Heart Failure (HF) has a high impact on health status and mortality.

  • Improving health status has increasing relevance in HF treatment.

  • Treatment induced health status improvements significantly correlated with a lower risk of HF hospitalization but not with the risk of cardiovascular or all-cause mortality.

  • Outcome trials assessing pharmacological treatments in chronic HF should continue to evaluate HF hospitalizations and mortality as robust means to assess treatment effects.

Abstract

Background

Heart failure (HF) is associated with poor health status, and high morbi-mortality. However, it is not well established how health status changes correlate with treatment effects on clinical outcomes. Our aim was to study the association between treatment-induced changes in health-status, assessed by Kansas City Cardiomyopathy Questionnaire 23 (KCCQ-23), and clinical outcomes in chronic HF.

Methods

Systematic search of phase III-IV pharmacological RCTs in chronic HF that assessed KCCQ-23 changes and clinical outcomes throughout follow-up. We studied the association between treatment induced changes in KCCQ-23 and treatment effects on clinical outcomes (HF hospitalization or cardiovascular death, HF hospitalization, cardiovascular death, and all-cause death) using weighted random-effects meta-regression.

Results

Sixteen trials were included, enrolling a total of 65,608 participants. Treatment induced KCCQ-23 changes were moderately correlated with treatment effects on the combined outcome of HF hospitalization or cardiovascular mortality (regression coefficient (RC) = −0.047, 95%CI: −0.085 to −0.009; R2 = 49%), a correlation that was mainly driven by HF hospitalization (RC = −0.076, 95%CI: −0.124 to −0.029; R2 = 56%). Correlations of treatment induced KCCQ-23 changes with cardiovascular death (RC = −0.029, 95%CI: −0.073 to 0.015; R2 = 10%) and all-cause death (RC = −0.019, 95%CI: −0.057 to 0.019; R2 = 0%) were weak and non-significant.

Conclusions

Treatment-induced changes in KCCQ-23 were moderately correlated with treatment-effects on HF hospitalizations but were not correlated with the effects on cardiovascular and all-cause mortality. Treatment-induced changes in patient-centered outcomes (i.e., KCCQ-23) may reflect non-fatal symptomatic changes in the clinical course of HF leading to hospitalization.

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.

References (47)

  • J. Butler et al.

    Minimally clinically important difference in health status scores in patients with HFrEF vs HFpEF

    JACC Heart Fail.

    (2022)
  • F.D.R. Hobbs et al.

    Impact of heart failure and left ventricular systolic dysfunction on quality of life. A cross-sectional study comparing common chronic cardiac and medical disorders and a representative adult population

    Eur. Heart J.

    (2002)
  • A.A. Voors et al.

    The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial

    Nat. Med.

    (2022)
  • M.E. Nassif et al.

    Dapagliflozin effects on biomarkers, symptoms, and functional status in patients with heart failure with reduced ejection fraction

    Circulation

    (2019)
  • Research C for DE

    Treatment for Heart Failure: Endpoints for Drug Development Guidance for Industry

    (2020)
  • M.J. Page et al.

    The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

    BMJ

    (2021)
  • J.A.C. Sterne et al.

    RoB 2: a revised tool for assessing risk of bias in randomised trials

    BMJ

    (2019)
  • S.D. Anker et al.

    Ferric carboxymaltose in patients with heart failure and iron deficiency

    N. Engl. J. Med.

    (2009)
  • K. Swedberg et al.

    Treatment of anemia with darbepoetin alfa in systolic heart failure

    N. Engl. J. Med.

    (2013)
  • J.J.V. McMurray et al.

    Angiotensin–neprilysin inhibition versus enalapril in heart failure

    N. Engl. J. Med.

    (2014)
  • B. Pitt et al.

    Spironolactone for heart failure with preserved ejection fraction

    N. Engl. J. Med.

    (2014)
  • P. Ponikowski et al.

    Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency†

    Eur. Heart J.

    (2015)
  • J.J.V. McMurray et al.

    Aliskiren, enalapril, or aliskiren and enalapril in heart failure

    N. Engl. J. Med.

    (2016)
  • 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.

    View full text