Importance Cardiovascular disease (CVD) is increased in people with HIV (PWH) and
is characterized by premature noncalcified coronary plaque. In the Randomized Trial
to Prevent Vascular Events in HIV (REPRIEVE), pitavastatin reduced major adverse cardiovascular
events (MACE) by 35% over a median of 5.1 years. Objective To investigate the effects
of pitavastatin on noncalcified coronary artery plaque by coronary computed tomography
angiography (CTA) and on inflammatory biomarkers as potential mechanisms for MACE
prevention. Design, Setting, and Participants This double-blind, placebo-controlled
randomized clinical trial enrolled participants from April 2015 to February 2018 at
31 US clinical research sites. PWH without known CVD who were taking antiretroviral
therapy and had low to moderate 10-year CVD risk were included. Data were analyzed
from April to November 2023. Intervention Oral pitavastatin calcium, 4 mg per day.
Main Outcomes and Measures Coronary CTA and inflammatory biomarkers at baseline and
24 months. The primary outcomes were change in noncalcified coronary plaque volume
and progression of noncalcified plaque. Results Of 804 enrolled persons, 774 had at
least 1 evaluable CTA. Plaque changes were assessed in 611 who completed both CT scans.
Of 611 analyzed participants, 513 (84.0%) were male, the mean (SD) age was 51 (6)
years, and the median (IQR) 10-year CVD risk was 4.5% (2.6-7.0). A total of 302 were
included in the pitavastatin arm and 309 in the placebo arm. The mean noncalcified
plaque volume decreased with pitavastatin compared with placebo (mean [SD] change,
-1.7 [25.2] mm(3) vs 2.6 [27.1] mm(3); baseline adjusted difference, -4.3 mm(3); 95%
CI, -8.6 to -0.1; P = .04; 7% [95% CI, 1-12] greater reduction relative to placebo).
A larger effect size was seen among the subgroup with plaque at baseline (-8.8 mm(3)
[95% CI, -17.9 to 0.4]). Progression of noncalcified plaque was 33% less likely with
pitavastatin compared with placebo (relative risk, 0.67; 95% CI, 0.52-0.88; P = .003).
Compared with placebo, the mean low-density lipoprotein cholesterol decreased with
pitavastatin (mean change: pitavastatin, -28.5 mg/dL; 95% CI, -31.9 to -25.1; placebo,
-0.8; 95% CI, -3.8 to 2.2). The pitavastatin arm had a reduction in both oxidized
low-density lipoprotein (-29% [95% CI, -32 to -26] vs -13% [95% CI, -17 to -9]; P
< .001) and lipoprotein-associated phospholipase A2 (-7% [95% CI, -11 to -4] vs 14%
[95% CI, 10-18]; P < .001) compared with placebo at 24 months. Conclusions and Relevance
In PWH at low to moderate CVD risk, 24 months of pitavastatin reduced noncalcified
plaque volume and progression as well as markers of lipid oxidation and arterial inflammation.
These changes may contribute to the observed MACE reduction in REPRIEVE.
