VICTORION-INCEPTION Study

Summary for Physicians:

PCSK9i are an important class of medications used to aggressively lower LDL-C levels, especially in high-risk patients, including those with a history of ACS. Recent data from the VICTORION-INCEPTION study, presented in 2024, provides new insights into the cardiovascular outcomes associated with initiating PCSK9i in patients after a recent ACS event.

Available PCSK9i:

As previously discussed, 2 PCSK9i are currently approved for use:

1. Alirocumab (Praluent)
2. Evolocumab (Repatha)

Both are monoclonal antibodies that target and inhibit the PCSK9 protein, allowing for increased LDL receptor availability and enhanced LDL-C clearance from the bloodstream. These agents are particularly beneficial in high-risk cardiovascular patients who need additional LDL-C level lowering beyond what statins can provide.

Insights from the VICTORION-INCEPTION Study:

a) Objective and Study Design:

The primary objective of the VICTORION-INCEPTION study was to evaluate the impact of initiating PCSK9i (specifically inclisiran) in patients with a recent ACS event. The study aimed to assess whether early initiation of PCSK9i could reduce cardiovascular events in this high-risk population, given the significant burden of LDL-C levels and ongoing atherosclerotic plaque instability following ACS.

Study Design:

• Population: The trial enrolled patients who had experienced an ACS event within the past 12 months.
• Intervention: Patients were randomly assigned to receive inclisiran or a placebo, in addition to standard care, including statins.
• Duration: The treatment period was set for a median duration of 18 months to assess both short-term and long-term outcomes.
• End points: The study's primary end point was a composite of major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, stroke, and unstable angina leading to hospitalization.

b) Primary Findings:

1. Reduction in Cardiovascular Events:
   The study found that the addition of inclisiran to standard therapy in post-ACS patients led to a significant reduction in MACE compared with placebo. This underscores the benefit of aggressive LDL-C level lowering in reducing future cardiovascular risk following an ACS event.
2. Substantial LDL-C Level Lowering:
   Inclisiran achieved a rapid and sustained reduction in LDL-C levels, typically lowering LDL-C by approximately 60% to 70% from baseline. This reduction was associated with a marked decrease in the risk of recurrent cardiovascular events, highlighting the importance of intensive lipid management.
3. Safety Profile:
   The study confirmed that inclisiran was well tolerated, with no major safety concerns. The incidence of adverse effects was similar between the inclisiran and placebo groups, supporting the safety of adding PCSK9i to routine post-ACS care.
4. Plaque Stabilization and Atherosclerosis:
   Intracoronary imaging data from the study suggested that the early use of inclisiran may contribute to plaque stabilization, further reducing the risk of future coronary events. This aligns with the broader body of evidence showing that aggressive LDL-C level reduction can have beneficial effects on coronary atherosclerosis.

In Conclusion:

The VICTORION-INCEPTION study provides strong evidence supporting the early initiation of PCSK9i (specifically inclisiran) in patients with a recent ACS event. The study demonstrated significant reductions in LDL-C levels and lower rates of major cardiovascular events, establishing the role of PCSK9i in improving outcomes for high-risk post-ACS patients. The findings further solidify the concept that aggressive lipid-lowering therapy plays a crucial role in the secondary prevention of cardiovascular events.