University of Leicester
PCSK9+in+HF-31-5-17.pdf (418.32 kB)

The PCSK9-LDL Receptor Axis and Outcomes in Heart Failure: BIOSTAT-CHF Subanalysis.

Download (418.32 kB)
journal contribution
posted on 2017-11-21, 15:46 authored by Antoni Bayes-Genis, Julio Núñez, Faiez Zannad, João Pedro Ferreira, Stefan D. Anker, John G. Cleland, Kenneth Dickstein, Gerasimos Filippatos, Chim C. Lang, Leong L. Ng, Piotr Ponikowski, Nilesh J. Samani, Dirk J. van Veldhuisen, Aeilko H. Zwinderman, Marco Metra, Josep Lupón, Adriaan A. Voors
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis progression. OBJECTIVES: The aim of this study was to determine whether the PCSK9-LDLR axis could predict risk in patients with heart failure (HF). METHODS: The BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure) is a multicenter, multinational, prospective, observational study that included patients with worsening HF signs and/or symptoms. The primary endpoints were all-cause mortality and the composite of mortality or unscheduled hospitalizations for HF. We implemented Cox proportional hazard regression to determine the simultaneously adjusted effect of PCSK9 and LDLR on both outcomes when added to the previously validated BIOSTAT-CHF risk scores. RESULTS: This study included 2,174 patients (mean age: 68 ± 12 years; 53.2% had a history of ischemic heart disease). Median (interquartile range) PCSK9 and LDLR levels were 1.81 U/ml (1.45 to 2.18) and 2.98 U/ml (2.45 to 3.53), respectively. During follow-up, 569 deaths (26.2%) and 896 (41.2%) composite endpoints were ascertained. A multivariable analysis, which included BIOSTAT-CHF risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.49; p = 0.020) and the composite endpoint (HR: 1.21; 95% CI: 1.05 to 1.40; p = 0.010). A similar analysis for LDLR revealed a negative association with mortality (HR: 0.86; 95% CI: 0.76 to 0.98; p = 0.025) and the composite endpoint (HR: 0.92; 95% CI: 0.83 to 1.01; p = 0.087). Including PCSK9 and LDLR improved risk score performance. CONCLUSIONS: The PCSK9-LDLR axis was associated with outcomes in patients with HF. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF.


This project was funded by a grant from the European Commission (FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29). Dr. Bayes-Genis was supported by grants from the Ministerio de Educación y Ciencia (SAF2014-59892), Fundació La MARATÓ de TV3 (201502, 201516), CIBER Cardiovascular (CB16/11/00403), and AdvanceCat 2014-2020; and has received board membership fees and travel expenses from Novartis, Roche Diagnostics, and Critical Diagnostics. Dr. Núñez has received board membership fees and travel expenses from Novartis, Roche Diagnostics, Abbott, Rovi and Vifor. Dr. Voors has received consultancy fees and/or research grants from Alere, Amgen, Bayer, Boehringer Ingelheim, Cardio3Biosciences, Celladon, GlaxoSmithKline, Merck/Merck Sharp & Dohme, Novartis, Servier, Stealth Peptides, Singulex, Sphingotec, Trevena, Vifor, and ZS Pharma. Dr. Anker has received grants from Vifor and Abbott Vascular; and fees for consultancy or speaking from Vifor, Bayer, Boehringer Ingelheim, Brahms, Janssen, Novartis, Servier, Stealth Peptides, and ASTRA. Dr. Filippatos has received committee fees and/or research grants from Novartis, Bayer, Vifor, and Servier. Dr. Lang has received consultancy fees and/or research grants from Amgen, Astra Zeneca, Merck Sharp & Dohme, Novartis, and Servier. Dr. van Veldhuisen has received board membership fees or travel expenses from Novartis, Johnson & Johnson, and Vifor. Dr. Metra has received consulting honoraria from Amgen, AstraZeneca, Bayer, Novartis, Relypsa, Servier, Stealth Therapeutics, and Trevena; and speaker fees from Abbott Vascular and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Bayes-Genis and Núñez contributed equally to this work.



Journal of the American College of Cardiology, 2017, 70 (17), pp. 2128-2136

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences


  • AM (Accepted Manuscript)

Published in

Journal of the American College of Cardiology


Elsevier for American College of Cardiology





Acceptance date


Copyright date


Available date


Publisher version


The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.