Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy

Area of Science:

• Cardiology
• Pharmacology
• Inflammation Research

Background:

• Statin therapy combined with PCSK9 inhibition effectively reduces LDL cholesterol and cardiovascular events.
• The role of residual inflammatory risk, measured by on-treatment high-sensitivity C-reactive protein (hsCRP), in patients on combined therapy is not well-defined.

Purpose of the Study:

• To evaluate residual inflammatory risk in patients receiving both statin therapy and bococizumab, a PCSK9 inhibitor.
• To assess the association between on-treatment hsCRP levels and cardiovascular event rates in this patient population.

Main Methods:

• A post hoc analysis of 9738 patients from the SPIRE-1 and SPIRE-2 trials was conducted.
• Patients received statin therapy plus bococizumab, with on-treatment hsCRP (hsCRP_OT) and LDL-C (LDL-C_OT) measured at 14 weeks.
• Cardiovascular events (myocardial infarction, stroke, unstable angina, cardiovascular death) were tracked.

Main Results:

• Bococizumab significantly reduced LDL-C by -60.5% at 14 weeks, while hsCRP showed minimal change.
• Patients with higher hsCRP_OT levels (>3 mg/L) had a significantly increased risk of cardiovascular events (HR 1.62) compared to those with hsCRP_OT <1 mg/L.
• No significant interaction was observed between hsCRP_OT levels and the relative risk reduction achieved with bococizumab.

Conclusions:

• Residual inflammatory risk, indicated by elevated on-treatment hsCRP, persists in patients treated with statins and PCSK9 inhibition.
• Higher hsCRP_OT levels are associated with a greater risk of cardiovascular events, even with intensive LDL-C lowering.
• These findings suggest that inflammatory pathways may contribute to cardiovascular risk independently of LDL-C levels in patients on combined therapy.