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

Antoni Bayes-Genis (Lead / Corresponding author), Julio Núñez, Faiez Zannad, João Pedro Ferreira, Stefan D. Anker, John G. F. Cleland, Kenneth Dickstein, Gerasimos S. Filippatos, Chim C. Lang, Leong Ng, Piotr Ponikowski, Nilesh J. Samani, Dirk J. van Veldhuisen, Aeilko H. Zwinderman, Marco Metra, Josep Lupón, Adriaan A. Voors

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Abstract

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.

Original languageEnglish
Pages (from-to)2128-2136
Number of pages9
JournalJournal of the American College of Cardiology
Volume70
Issue number17
Early online date16 Oct 2017
DOIs
Publication statusPublished - 24 Oct 2017

Keywords

  • Heart failure
  • LDLR
  • Low-density lipoprotein receptor
  • PCSK9
  • Proprotein convertase subtilisin/kexin type 9

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    Bayes-Genis, A., Núñez, J., Zannad, F., Ferreira, J. P., Anker, S. D., Cleland, J. G. F., Dickstein, K., Filippatos, G. S., Lang, C. C., Ng, L., Ponikowski, P., Samani, N. J., van Veldhuisen, D. J., Zwinderman, A. H., Metra, M., Lupón, J., & Voors, A. A. (2017). The PCSK9-LDL Receptor Axis and Outcomes in Heart Failure: BIOSTAT-CHF Subanalysis. Journal of the American College of Cardiology, 70(17), 2128-2136. https://doi.org/10.1016/j.jacc.2017.08.057