Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition on Arterial Wall Inflammation in Patients With Elevated Lipoprotein(a) (Lp(a))

Summary

A study to assess the effects of proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibition on the arterial wall inflammation in patients with elevated lipoprotein(a).

Timeline

Start

2016-04-14

Primary completion

2018-04-05

Completion

2018-04-05

Outcome

Missed primary endpoint

registry analysis (superiority test); Placebo vs Evolocumab 420 mg QM; p = 0.18; LS Mean Treatment Difference -3.00 (95% CI -7.40 to 1.39); Multivariate regression model NCT02729025 ↗

Publications

• Background Stiekema LCA, Stroes ESG, Verweij SL, Kassahun H, Chen L, Wasserman SM, Sabatine MS, Mani V, Fayad ZA. Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment. Eur Heart J. 2019 Sep 1;40(33):2775-2781. doi: 10.1093/eurheartj/ehy862.
• Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.
• Zhang X, Stiekema LCA, Stroes ESG, Groen AK. Metabolic effects of PCSK9 inhibition with Evolocumab in subjects with elevated Lp(a). Lipids Health Dis. 2020 May 11;19(1):91. doi: 10.1186/s12944-020-01280-0.
• Stiekema LCA, Prange KHM, Hoogeveen RM, Verweij SL, Kroon J, Schnitzler JG, Dzobo KE, Cupido AJ, Tsimikas S, Stroes ESG, de Winther MPJ, Bahjat M. Potent lipoprotein(a) lowering following apolipoprotein(a) antisense treatment reduces the pro-inflammatory activation of circulating monocytes in patients with elevated lipoprotein(a). Eur Heart J. 2020 Jun 21;41(24):2262-2271. doi: 10.1093/eurheartj/ehaa171.

Drugs

Indications