Background
REPRIEVE and its Mechanistic Substudy established that pitavastatin prevents major adverse cardiovascular events and reduces noncalcified coronary plaque (NCP) on coronary CT angiography (CTA) among PWH with low-to-moderate traditional ASCVD risk. Here we assess heterogeneity of pitavastatin effects on NCP (density <350 HU) volume and plaque composition, categorized by density (<130HU fibrofatty, 130-350 HU fibrous, >350 HU calcified).
Methods
In 273 REPRIEVE Substudy participants randomized to pitavastatin calcium 4mg/day (N=140) or placebo (N=133) with preexisting coronary plaque on CTA, we evaluated the effect of pitavastatin on plaque composition, and effect modification by risk factors, including demographic and behavioral characteristics, ASCVD risk score, cardiovascular/metabolic factors, and HIV-related health history. Log-linear models, incorporating interactions between risk factors and treatment group, were used to analyze relative changes from baseline over 24 months. Heterogeneity of treatment effects were identified via interaction tests with P<0.10. All effects described are geometric mean ratio (GMR) between the pitavastatin and placebo groups, adjusting for risk factors and baseline plaque volumes.
Results
Participants were median age 52, 90% male, 61% white, 28% black or African American. The relative change from baseline in NCP with pitavastatin was 9% lower, indicating a greater reduction, than with placebo (GMR 0.91, 95% CI[0.82,1.02]). Pitavastatin showed a greater volume-reducing effect on fibro-fatty plaque (0.69 [0.49, 0.96]), with a marginal effect on fibrous plaque (0.92 [0.78, 1.08]) and a trend towards increased volume of calcified plaque (1.29 [0.85, 1.96]). Some heterogeneity in pitavastatin effects on NCP volume was observed. The volume-reducing effect of pitavastatin on NCP was greater among females (0.49[0.25, 0.96]), Hispanic or Latinos (0.55[0.38, 0.79]), those with systolic blood pressure >140 mmHg (0.38[0.20,0.72]), and those using non-statin lipid-lowering therapy (0.50[0.28, 0.92]). HIV-related and other factors did not relate to plaque composition changes.
Conclusions
These exploratory results suggest pitavastatin effects on NCP vary by demographic and cardiovascular risk factors; modification of statin effects by HIV risk factors was not apparent. The effect of pitavastatin appears greatest in reducing volume of fibrofatty plaque, which is thought to be the most biologically active component, and may increase plaque density.