Among people living with HIV receiving antiretroviral therapy, those taking 4-mg pitavastatin daily were 35% less likely than those taking placebo to experience a major cardiovascular event over 5 years of follow-up.
Among people living with HIV, those who received pitavastatin were 35% less likely to experience a major cardiovascular event compared with those who received placebo, according to a study published in The New England Journal of Medicine.1
The phase 3 Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) included 7769 participants with HIV who had a low to moderate risk of cardiovascular disease (CVD) and were receiving antiretroviral therapy (ART). Participants were randomized to receive either 4 mg of pitavastatin calcium or placebo daily. Major cardiovascular events included cardiovascular-related death, myocardial infarction (MI), stroke, transient ischemic attack, peripheral arterial ischemia, revascularization, hospitalization for unstable angina, or death from an unknown cause.
The study had a median (IQR) follow-up of 5.1 (4.3-5.9) years—stopped early due to observed efficacy—and participant age of 50 (45-55) years. Based on available data of 5997 participants, the median CD4 count was 621 cells/mm3 (448-827), and the HIV RNA value for 5250 (87.5%) participants was fewer than 20 copies/mL. Additionally, the median LDL cholesterol level at screening was 108 (87-128) mg/dL or 2.79 (2.25-3.31) mmol/L. The authors converted these values by multiplying the mg/dL measurement by 0.02586.
By the time of the final report, there were 2910 participants in the treatment group and 2754 in the placebo group.
The study demonstrated a 35% lower incidence of major adverse cardiovascular events overall—the study's primary outcome—with an incidence of 4.81 per 1000 person-years in the pitavastatin group and 7.32 per 1000 person-years in the placebo group (HR, 0.65; 95% CI, 0.48-0.90; P = .002).
“This observed reduction was larger than that predicted by the Cholesterol Treatment Trialists’ Collaboration on the basis of the achieved reduction in LDL cholesterol levels,” the study authors said, citing a meta-analysis published in 2010.2 “This finding suggests effects on cardiovascular risk beyond those associated with the lowering of LDL cholesterol alone.”
The authors observed muscle-related symptoms in 91 (2.3%) participants in the pitavastatin group and in 53 (1.4%) participants in the placebo group. They also recorded diabetes onset in 206 (5.3%) and 155 (4.0%) participants, respectively.
Of the 5997 participants, 63 received an MI diagnosis, with 50 of these cases being type 1 MI and the other 13 being type 2. According to the authors, the incidence of major adverse cardiovascular events was not affected by COVID-19 infection, as only 1 case of ischemic stroke was deemed related to COVID-19.
Sensitivity and supporting analyses that excluded deaths without a known cause also favored the pitavastatin group (HR, 0.65; 95% CI, 0.48-0.87), as well as analyses that were adjusted for cardiovascular and HIV risk factors. Sensitivity analyses accounting for missing data also showed results consistent with those for the primary outcome “under realistic assumptions for the missing data but not under extreme assumptions,” according to the authors. Additionally, per-protocol analysis results showed that the effect of pitavastatin compared with placebo was similar to the primary results (HR, 0.67; 95% CI, 0.50-0.89).
According to the authors, these results may be globally generalizable to people with HIV aged 40 to 75 years who are receiving ART and are at low to moderate risk for atherosclerotic CVD, as the REPRIEVE population was 65.2% non-White and 31.1% female.
“Although persons with HIV infection who have known cardiovascular disease or who are at higher risk should be receiving statin therapy on the basis of revised existing guidelines, further evidence has been needed to support recommendations for the prescribing of statins in those at low or moderate risk,” the authors said. “Our identification of benefit in the groups at lower or moderate risk now establishes the need to expand this recommendation. It also remains important to optimize lifestyle factors beyond lipids, including smoking, in this population.”
1. Grinspoon SK, Fitch KV, Zanni MV, et al. Pitavastatin to prevent cardiovascular disease in HIV infection. N Engl J Med. Published online July 23, 2023. doi:10.1056/NEJMoa2304146
2. Cholesterol Treatment Trialists’ (CTT) Collaboration; Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. doi:10.1016/S0140-6736(10)61350-5