The slide on the left shows the natural course cardiovascular disease - a progressive disease manifesting as a recurring cycles of heart attacks and strokes. Without prevention, The slide on the right shows the effect of optimal preventive treatment on the composition of the plague itself - arresting plaque progression and causing plaque stabilization.
The first landmark statin clinical trial was the 4S Study published in 1994. The most recent landmark clinical statin trial is the JUPITER Trial in 2008. Between 1994 and 2008, there were over a dozen clinical trials. Cumulatively, there are over 1 million patient-years of clinical trial data confirming repeatedly that statin reduces heart attacks, strokes, cardiac deaths, stents, heart bypass surgeries, hospitalizations, etc.
Successful prevention involves addressing all modifiable risk factors including adopting a healthier lifestyle. This means quitting smoke, healthier diet, more physical activity, blood pressure and diabetes control, in addition to lipid management. While all are important, the foundation is prevention in high risk patients is lipid therapy. Analysis of the STENO-2 trial showed that cholesterol treatment accounted for more than 70% of cardiovascular risk reduction.
Some high risk patients may need more aggressive cholesterol treatment to maximize risk reduction. Many patients with low HDL-C, high triglycerides, diabetes and metabolic syndrome have significant residual risk even after optimal LDL-C treatment. One reason is a discordantly high LDL particle concentration as shown above - same LDL-C at 90 but higher LDL-P at 1500 vs 800.
Plaques that rupture and cause heart attack, stroke and sudden cardiac death are characterized by a large cholesterol-filled necrotic core. An example is shown above using high resolution MRI (with the red arrow). While treatment of any risk factor can slow down plague progression, only aggressive lipid therapy has been shown to reliably induce plaque regression. The above slide demonstrates the potency of advanced cholesterol therapy in inducing plaque regression after just three years of aggressive treatment.
