Pitavastatin Reduces Arterial Plaque, Inflammation in PWH at Moderate CVD Risk

For people with HIV (PWH) who have a low to moderate risk of cardiovascular disease (CVD) taking pitavastatin for 2 years helped decrease the amount of plaque buildup in their arteries that isn't made of calcium, while also slowing down the growth of this plaque. Pitavastatin also reduced markers of lipid oxidation and inflammation in the arteries in these patients.

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These findings were published in JAMA Cardiology as a mechanistic substudy of the REPRIEVE randomized clinical trial. According to the authors, these improvements might be part of the reason why there was a lower rate of major adverse cardiovascular events (MACE) in the REPRIEVE study.

PWH have an increased prevalence of CVD compared with individuals without HIV, and it often presents with premature noncalcified coronary plaque. In the REPRIEVE study, the use of pitavastatin led to a significant 35% reduction in MACE over a median duration of 5.1 years. With this in mind, researchers sought to examine how pitavastatin affects noncalcified coronary artery plaque using coronary computed tomography angiography (CTA) and assess its impact on inflammatory biomarkers as potential mechanisms for preventing MACE.

To do so, they conducted a double-blind, placebo-controlled randomized clinical trial at 31 clinical research sites across the US from April 2015 to February 2018. Participants included PWH who did not have diagnosed CVD, had a low to moderate 10-year risk of CVD, and were undergoing antiretroviral therapy.

Of the 804 individuals initially enrolled in the substudy, 774 had at least 1 coronary CTA that could be evaluated, and of that group, plaque changes were evaluated in 611 participants who completed both CT scans. Of these analyzed participants, 513 (84.0%) were male, with a mean (SD) age of 51 (6) years and a median (IQR) 10-year CVD risk of 4.5% (2.6-7.0). In the intervention arm, 302 PWH took 4 mg oral pitavastatin calcium per day for 24 months, while 309 took placebo for the same timeframe.

The average volume of noncalcified plaque decreased when participants took pitavastatin compared with those who took the placebo, with a mean (SD) change of –1.7 (25.2) mm³ in the treatment group vs 2.6 (27.1) mm³ in the placebo group (baseline adjusted difference, –4.3 mm³; 95% CI, –8.6 to –0.1; P = .04), representing a 7% (95% CI, 1-12) greater reduction than the placebo group.

Particularly, the researchers observed a more significant reduction in the subgroup with plaque at the study's start (–8.8 mm³; 95% CI, –17.9 to 0.4), and the 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). Additionally, pitavastatin led to a decrease in mean low-density lipoprotein cholesterol (LDL-C) compared with placebo, with a mean change of –28.5 mg/dL (95% CI, –31.9 to –25.1) in the pitavastatin arm and –0.8% (95% CI, –3.8 to 2.2) in the placebo arm.

The pitavastatin group also exhibited a 29% reduction in oxidized LDL (95% CI, –32 to –26) and a 7% reduction in lipoprotein-associated phospholipase A2 (95% CI, –11 to –4) compared with the placebo group at 24 months.

Reference

Lu MT, Ribaudo H, Foldyna B, et al; REPRIEVE Trial Writing Group. Effects of pitavastatin on coronary artery disease and inflammatory biomarkers in HIV: mechanistic substudy of the REPRIEVE randomized clinical trial. JAMA Cardiol. Published online February 21, 2024. doi:10.1001/jamacardio.2023.5661