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

Journal of the American College of Cardiology
Roeland HuijgenGilles Lambert

Abstract

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. 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. 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). 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. PCSK9 levels pre...Continue Reading

References

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Citations

Oct 12, 2013·Clinical Drug Investigation·Yuan-Lin GuoJian-Jun Li
Nov 7, 1995·Biochimica Et Biophysica Acta·G E Baida, N P Kuzmin
Aug 22, 2012·Current Opinion in Lipidology·David A MaraisGilles Lambert
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Jun 1, 2021·Hellenic Journal of Cardiology : HJC = Hellēnikē Kardiologikē Epitheōrēsē·Jixiang WangYin Liu

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