Can Pitavastatin Lower the Risk of Cardiovascular Events in Patients with HIV?

In the phase 3 Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) trial, researchers found that those with HIV infection and a low-to-moderate risk of cardiovascular events who were administered antiretroviral therapy (ART) and received pitavastatin had a lower risk of major adverse cardiovascular events than those who received placebo over a median follow-up of 5.1 years.

Pitavastatin is a statin therapy that reduces low-density lipoprotein (LDL) cholesterol, but it not typically given to those with low-to-moderate risk of cardiovascular events. The researchers, however, wanted to investigate pitavastatin because, importantly, it does not interact with ART. This is notable because, for those with HIV, the risk of cardiovascular disease—including myocardial infarction and stroke—is twice as high as those in the general population. And yet this patient population is generally not offered a cardiovascular prevention medication. In fact, there are no cardiovascular disease prevention guidelines specifically tailored to those with HIV.

Enter Grinspoon and colleagues, who randomly assigned 7769 participants with HIV infection and low-to-moderate risk of cardiovascular disease who were administered ART and received daily pitavastatin calcium (at a dose of 4 mg) or placebo. The median age of the study participants was 50 years.

In the REPRIEVE trial, the authors defined the primary outcome as the occurrence of a major adverse cardiovascular event, such as death from a cardiovascular event, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack, peripheral arterial ischemia, revascularization, or death from an undetermined cause.

The incidence of a major adverse cardiovascular event was 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 = 0.002). Muscle-related symptoms occurred in 91 participants (2.3%) in the pitavastatin group and in 53 (1.4%) in the placebo group; diabetes mellitus occurred in 206 (5.3%) and in 155 (4%) participants, respectively.

Interestingly, the trial was stopped early after the researchers found that participants in the pitavastatin group had a lower incidence of major adverse cardiovascular events than those in the placebo group, with a hazard reduction of 35% over a median of 5.1 years of follow-up. The therapeutic benefit was similar for men and women as well as for those from different international regions.

“Our results may be generalizable to the large global population of persons with HIV infection between the ages of 40 and 75 years who are receiving ART and who are at low-to-moderate risk for atherosclerotic cardiovascular disease,” the authors wrote.

Additionally, the authors found that their trial results may have revealed therapeutic benefits beyond LDL cholesterol reduction.

“In addition to the lowering of LDL cholesterol levels, statin therapy reduces measures of immune activation and inflammation in persons with HIV infection, which suggests potential mechanisms by which statins benefit this population beyond the effects of LDL-cholesterol lowering,” the authors wrote.

In their study, the authors noted several limitations, namely that the results are specific to pitavastatin. Although other statins may have similar protective effects, future studies still need to examine several variables including its cost, efficacy, and safety.

Even with these limitations, the trial results suggest that current recommendations regarding those with HIV and low-to-moderate risk of cardiovascular events could be expanded.

“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 wrote. “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.”

Reference:

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