Abstract 13244: Is Early Statin Treatment Justified Before Formation of Atherosclerotic Plaques?

Objective: Although statin is recommended for secondary prevention of acute coronary syndrome regardless of the baseline LDL-cholesterol level, statin administration in the pre-intervention phase has not been established as a routine strategy because of lack of sufficient evidence. We conducted an animal study comparing the results of early statin administration vs. no such administration in pigs susceptible to atherosclerosis. Methods and Results: Three-month-old LDL receptor knockout (LDLR-/-) pigs with no atherosclerosis were divided into two groups: those fed an atherosclerotic diet consisting of 15% fat and 1.5% cholesterol for 4 months (control group) and those fed the same diet but given oral pitavastatin (40 mg/day) (early treatment group). Human-like unstable plaques developed in the coronary arteries of the control pigs. After in vivo intravascular ultrasound (IVUS) examination, pigs’ coronary arteries were harvested and cut into 1-cm sections for pathological analyses. Blood cholesterol levels (mg/dL) did not differ significantly between the control group and early treatment group: total cholesterol, 931±45 vs 881±81; VLDL, 539±26 vs 514±59; LDL, 277±35 vs 245±36; HDL, 89±3 vs 95 ± 6, respectively). IVUS and pathological examination revealed similar lumen areas but a significant reduction in plaque and vessel volume in the early treatment group. The proportion of atherosclerotic lesions was 80% in the control group and 67% in the early treatment group (P=0.01). Most lesions (87%) in the early treatment group were early-stage lesions (Stary types I-III), whereas 45% of lesions in the control group were early-stage lesions (P<0.01). Only 1% of lesions were considered unstable plaques (Stary type VI lesions) in the early treatment group (vs 10% in the control group) (P<0.01). With respect to instability, thin-cap fibroatheroma was 40% in the control group vs. 8% in the early treatment group (P<0.01), intraplaque hemorrhage was 11% vs 1% (P<0.01), and calcification was 22% vs 1% (P<0.01). Conclusions: Our large-animal experiment provides support for early statin treatment before occurrence of atherosclerosis. Early statin treatment appears to retard development of coronary artery atherosclerosis and maintain lesion stability.