Benefits of PCSK9i Demonstrated in Intracoronary Imaging

The discussion shifts toward the use of PCSK9 inhibitors and their impact on coronary disease, particularly the effects on plaque within the arteries. Studies have shown that aggressively lowering low-density lipoprotein (LDL) using PCSK9 inhibitors reduces lipid core volume within plaques. More importantly, these inhibitors increase the thickness of the fibrous cap, which is crucial because the rupture of a thin fibrous cap is a key trigger for acute coronary events. This is a shift in understanding from earlier practices, where we thought plaque size alone determined risk.

In fact, research now suggests that 75% of acute myocardial infarctions occur from lesions that were less than 50% blocked the day before the infarction. High lipid content in plaques causes inflammation, which weakens the fibrous cap. This leads to plaque rupture, exposing thrombogenic material and triggering a clot, which causes a complete blockage. By reducing LDL levels aggressively, PCSK9 inhibitors lower the lipid core and reduce plaque inflammation, stabilizing the fibrous cap and preventing rupture. This treatment approach not only addresses the plaque but also the underlying inflammation, providing a broader and more effective treatment for coronary artery disease. Despite the lack of significant changes in lesion size in angiograms, these therapies have been shown to reduce acute myocardial infarction by 50%, highlighting the importance of treating the disease at a cellular level.