PCSK9 Inhibitors

This discussion highlights the evolving landscape of lipid management, especially in high-risk patients following an acute cardiovascular event. While statins remain the foundational therapy, the availability of newer agents, particularly PCSK9 inhibitors and inclisiran, has significantly expanded the treatment options. These therapies offer potent low-density lipoprotein (LDL)–lowering capabilities beyond what statins alone can achieve, enabling more personalized and effective prevention strategies.

PCSK9 inhibitors like evolocumab and alirocumab work by neutralizing the PCSK9 protein, which otherwise reduces LDL receptor availability. This mechanism enhances the liver’s ability to clear LDL from the bloodstream. Inclisiran, on the other hand, is a small interfering RNA that acts upstream by preventing the production of PCSK9 altogether. Its longer dosing interval also provides a convenient option for long-term lipid control. These innovations represent a new era in preventive cardiology, offering powerful tools to reduce cardiovascular risk, particularly in patients who are unable to reach target LDL levels with statins alone.

Despite the scientific progress, implementation still lags. Current guidelines and payer policies often promote a stepwise approach—starting with a statin, then adding ezetimibe, and only later considering PCSK9 inhibitors. This process can be slow and inefficient, especially given how predictable LDL response to therapy can be. Clinicians can often foresee that a statin alone won’t be sufficient for certain high-risk patients, particularly following an ACS event. However, the system isn’t built to support proactive combination therapy from the outset. This delay in treatment optimization leaves patients vulnerable during a critical risk window. As other fields move toward early and aggressive combination therapies, lipid management should evolve in the same direction to close the gap between guideline recommendations and real-world outcomes.