Plasma PCSK9 levels and clinical outcomes in the TNT (Treating to New Targets) trial: a nested case-control study.

Abstract

OBJECTIVES:

The purpose of this study was to investigate whether high levels of circulating proprotein convertase subtilisin kexin type 9 (PCSK9) would increase cardiovascular risk in statin-treated patients.

BACKGROUND:

Statins activate low-density lipoprotein (LDL) receptor gene expression, thus lowering plasma LDL levels. But statins also activate the expression of PCSK9, a secreted inhibitor of the LDL receptor, thereby limiting their beneficial effects.

METHODS:

We have measured the plasma PCSK9 levels of 1,613 patients with stable coronary heart disease enrolled in the Treating to New Targets study, a randomized trial that compared the efficacy of high- versus low-dose atorvastatin. After a run-in period with atorvastatin 10 mg daily, patients were randomized to either continue with 10 mg or be up-titrated to 80 mg of atorvastatin, and followed during 5 years for major cardiovascular events (MCVEs).

RESULTS:

Circulating PCSK9 levels measured at randomization were predictive of clinical outcomes in the group randomized to remain on atorvastatin 10 mg (p = 0.039), but not in the group that intensified atorvastatin treatment to 80 mg (p = 0.24). Further, PCSK9 levels measured 1 year post-randomization did not change upon increase of the statin dose.

CONCLUSIONS:

PCSK9 levels predict cardiovascular events in patients treated with low-dose atorvastatin. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; NCT00327691).

• Authors: Roeland Huijgen, S Matthijs Boekholdt, Benoit J Arsenault, Weihang Bao, Jean-Michel Davaine, Fatiha Tabet, Francine Petrides, Kerry-Anne Rye, David A DeMicco, Philip J Barter, John J P Kastelein, Gilles Lambert
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 59 Issue 20 Pg. 1778-84 (May 15 2012) ISSN: 1558-3597 [Electronic] United States
• PMID: 22575316 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Retracted Publication)
• Copyright: Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Heptanoic Acids
• Pyrroles
• Atorvastatin
• PCSK9 protein, human
• Proprotein Convertase 9
• Proprotein Convertases
• Serine Endopeptidases

Topics

• Aged
• Atorvastatin
• Biomarkers (blood)
• Case-Control Studies
• Coronary Disease (blood, diagnosis, drug therapy)
• Double-Blind Method
• Drug Delivery Systems (methods)
• Female
• Follow-Up Studies
• Heptanoic Acids (administration & dosage)
• Humans
• Male
• Middle Aged
• Proprotein Convertase 9
• Proprotein Convertases (blood)
• Pyrroles (administration & dosage)
• Serine Endopeptidases (blood)
• Treatment Outcome