The low risk of cardiovascular events was observed in all relevant subgroups, including in both males and females with HIV.
Patients with HIV administered antiretroviral therapy (ART) and who were treated with pitavastatin had a lower risk of a major adverse cardiovascular event (MACE) than those who received a placebo, according to the results of a study published in The New England Journal of Medicine.
Criteria for participation in the phase 3 trial included a diagnosis of HIV infection, being 40 to 75 years of age, and being a recipient of stable ART. All of the participants had a low-to-moderate risk of atherosclerotic cardiovascular disease, the investigators wrote.
Participants were randomized and assigned in a 1:1 ratio to receive oral pitavastatin calcium or an identical placebo. The primary outcome of the study was the occurrence of a MACE, which included cardiovascular death, myocardial infarction, and hospitalization for unstable angina, the study authors wrote.
After screening more than 10,000 participants over a 4-year period, 7769 individuals were selected to participate in the study, with 3888 in the pitavastatin group and 3881 in the placebo group. The median duration of follow-up was 5.1 years (IQR, 4.3 to 5.9) and a total of 6452 participants (83.0%) remained in the follow-up.
Of the participants examined at the follow-up, 5664 (2910 [74.8%] in the pitavastatin group and 2754 [71.0%] in the placebo group) continued to receive their randomized treatment at the time of the study being published. In analyzing the primary outcome, the researchers found that the occurrence of MACE was 4.81 per 1000 person-years in the pitavastatin group and 7.32 per 1000 person-years in the placebo group (hazard ratio, 0.65; 95% CI, 0.48 to 0.90; P = 0.002). Researcher examined a generally consistent trend among any subgroups.
The incidence of a MACE or death from any cause was 9.18 per 1000 person-years in a pitavastatin group and 11.63 per 1000 person-years in the placebo group (hazard ratio, 0.79; 95% CI, 0.65 to 0.96). Deaths from non-cardiovascular causes were seen in 82 participants in the pitavastatin group and 81 in the placebo group.
The researchers discussed how the risk of atherosclerotic cardiovascular disease was increased among all people with HIV infection, even those who are younger or are at lower traditional risk for cardiovascular disease. Notably, the investigators stopped the trial early after they discovered their results, with a hazard reduction of 35% over a median of 5.1 years of follow-up.
Among subgroups, efficacy in men and women appeared to be similar, which provides reassurance about the relative statin effectiveness in that population due to the high risk of HIV-associated cardiovascular disease among women, the study authors discussed.
Importantly, the investigators found that pitavastatin appeared to have an acceptable adverse effect (AE) profile, which can be seen as resulting in the low levels of discontinuation due to AEs that was observed during the trial.
The trial had several limitations that the investigators discussed. Most prominently, their study was limited to pitavastatin, but they noted that other statins may have similar protective effects, and that those who live in areas where pitavastatin is not available may reasonably use other statins that don’t interact with ART.
“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. Our identification of benefit in the groups at lower or moderate risk now establishes the need to expand this recommendation,” the study researchers concluded.
Grinspoon SK MD, Fitch KV MSN, Zanni MV MD, et al. Pitavastatin to prevent cardiovascular disease in HIV infection. New Engl Journ Med. 2023. doi:10.1056/NEJMoa2304146