Background: Statins slow progression of carotid intima-media thickness (IMT) and prevent cardiovascular events in HIV uninfected subjects. To what degree they may slow progression of carotid disease in HIV-infected patients on antiretroviral therapy (ART) is unknown.
Methods: SATURN-HIV was a 96-week double-blind, randomized clinical trial of 10 mg daily rosuvastatin versus placebo among 147 HIV-infected subjects on stable ART with LDL-cholesterol ≤130mg/dL and evidence of heightened T-cell activation (CD8+CD38+HLA-DR+ ≥19%) or increased inflammation (high sensitivity C-reactive protein ≥2mg/L). Randomization was stratified by protease inhibitor use and coronary artery calcium (CAC) score. Common carotid artery IMT (CCA-IMT) and presence of carotid plaque were assessed by ultrasound using semi-automated edge detection software. CAC was measured by gated cardiac CT. The study was designed to have >80% power to detect a 0.118 mm difference in the primary outcome of mean-mean CCA-IMT change. All analyses were intent to treat.
Results: Median (Q1, Q3) age was 46 (40, 53) years; 78% were male and 68% African American; 49% were on a protease inhibitor. Baseline median CCA-IMT was similar between groups [0.664 (0.624, 0.772) vs. 0.670 (0.602, 0.752) mm, statin vs. placebo, p=0.50]. At baseline, at least a third had carotid plaque (33% vs. 43%, statin vs. placebo, p=0.24) or detectable CAC (33% vs. 40%, statin vs. placebo, p=0.40). Overall, CCA-IMT progression was slower than anticipated [mean (standard deviation) 96 week change +0.015 (0.071) mm]. Within the placebo group, mean CCA-IMT progressed significantly over 96 weeks, but was unchanged in the statin group (see Figure). Mean difference in annualized rate of CCA-IMT change between groups was 0.014 mm/yr. Among those without carotid plaque at baseline, there was no difference in development of new plaque by week 96 (4.9% vs. 6.5%, statin vs. placebo, p=0.82). Among those without CAC at baseline, there was a trend towards more detectable CAC after 96 weeks of statin (15% vs. 6%, statin vs. placebo, p=0.19).
Conclusions: Rosuvastatin 10 mg daily appears to halt progression of carotid IMT in HIV-infected patients on ART with low LDL-cholesterol and high levels of immune activation. The effect on IMT progression is similar in magnitude to studies of HIV-uninfected populations and provides further justification for clinical outcomes trials in this population.