Abstract 1195: Proatherogenic Impact of the ACAT Inhibitor Pactimibe in Patients with Coronary Artery Disease and Multiple Risk Factors: Insights from the ACTIVATE study
Background: The acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor pactimibe has a detrimental effect on plaque progression. This study investigated whether the presence of established or emerging risk factors (RF) influenced the impact of this therapy.
Methods: 408 subjects with angiographic coronary artery disease (CAD) treated with pactimibe or placebo underwent serial assessment of plaque progression by intravascular ultrasound. The relationship between the number of RF (hypertension, hypercholesterolemia, diabetes, smoking), C-reactive protein (CRP) and body mass index (BMI) at baseline and changes in percent atheroma volume (PAV) and total atheroma volume (TAV) was investigated.
Results: Subjects had a mean age 59.4+/-9.7 years, 71.1% male, BMI of 30.7+/-5.6 kg/m2, high incidence of hypertension (73.8%), hypercholesterolemia (85.5%), diabetes (26.5%), metabolic syndrome (50%), smoking (20.6%) and CRP of 2.8 mg/L. 3.4% of subjects had 0 RF, 63.5% 1–2 RF and 33.1% 3– 4 RF. No significant differences were noted with regard to the change in PAV with either placebo or pactimibe in any subgroup. Pactimibe had a detrimental effect on the change in TAV in subjects with 3– 4 RF (3.5+/-17.8 v -4.2+/-15 mm3, p=0.0075) but not 0–2 RF (-3.6+/-21.1 v -5.4+/-18.3 mm3, p=0.33). Pactimibe had an adverse effect on the change in TAV in subjects with BMI>30 kg/m2 (0.8+/-21.4 v -5.5+/-16.3 mm3, p=0.03) but not subjects with a BMI<30 kg/m2 (-3.0+/-18.9 v -4.7+/-18.1 mm3, p=0.50). A trend towards an adverse effect with pactimibe on the change in TAV was also seen in subjects with baseline CRP>3 mg/L (1.3+/-19.2 v -3.3+/-17.9 mm3, p=0.08) while having no impact in the setting of CRP<3 mg/L (-4.0+/-21.3 v -6.5+/-16.8 mm3, p=0.37). The change in TAV differed significantly between patients with the combination of 0–2 RF/CRP<3 mg/L or 3– 4 RF/CRP>3 mg/L in pactimibe (-5.3+/-22 v 4.8+/-17.7 mm3, p=0.007) but not placebo (-6.4+/-17.9 v -2.8+/-16.4 mm3, p=0.28) treated patients.
Conclusion: A proatherogenic effect of pactimibe was demonstrated in subjects with RF clustering, obesity and a combination of RF and elevated CRP. This suggests that the detrimental impact of pactimibe is primarily observed in high risk individuals with CAD.