REPRIEVE Stopped: Big MACE Reductions With Statins in HIV+ Subjects

A daily statin can reduce the risk of new-onset cardiovascular disease in people living with HIV, according to preliminary results from the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) trial. Top-line results for this large, National Institutes of Health-funded study were released yesterday following an interim analysis indicating that subjects randomized to pitavastatin had a 35% lower risk of major adverse cardiovascular events compared with those receiving a placebo. 

Speaking with TCTMD, co-principal investigator Steven K. Grinspoon, MD (Harvard Medical School, Boston, MA), clarified that the reduction in MACE occurred within a mean follow-up of 5 years and was “even beyond what we expected—a very robust signal.”

Right now, use of statins in HIV-positive patients with no cardiovascular risk factors would typically only happen at physician discretion.

As co-principal investigator Pamela Douglas, MD (Duke Clinical Research Institute, Durham, NC), pointed out to TCTMD, for now HIV is considered merely a “risk modifier” in the current primary prevention guidelines. “REPRIEVE basically says that the usual considerations of LDL and risk score are less relevant in this population,” she said in an email.

Younger Patients, No Other Risk Factors

Many HIV patients are younger than the typical patient population seeing a cardiologist or prescribed statins today. “What [REPRIEVE] does is it expands our knowledge to suggest that patients 40 to 75 who have moderate-to-low risk, who have HIV and a normal LDL will benefit from statin therapy,” Grinspoon said. “I hope guidelines will be expanded to include this.”

Launched in 2015, REPRIEVE randomized 7,769 HIV-positive subjects at low or moderate risk of developing cardiovascular disease to pitavastatin or placebo; more than 30% of the cohort are women. Subjects enrolled at one of 120 sites in 12 countries across North and South America, Asia, Africa, and Europe are being followed for up to 8 years.

It is the first, large-scale clinical study to test a primary CVD prevention strategy in people living with HIV and, according to Grinspoon, represents a major new treatment for these patients.

“Although the life span gap has been closing, there is still a gap—patients with HIV still don't live quite as long as non-HIV patients. And although this is getting a little better, the comorbidity gap has not been really closing, and one of the most common comorbidities is cardiovascular disease,” he explained.

Rates of CVD in HIV-positive patients are roughly twice that seen in the general population. “For years, the main thing was that we needed to get the virus under control, and studies like SMART showed us that treatment with antiretroviral therapy [ART], with good control of the virus, actually did lead to a reduction in comorbidities as well as viral infections.”

Over time, Grinspoon said, “I think the story has evolved from thinking we need to get everyone on ART and fully suppress the virus as much as possible, to now thinking that this may not be sufficient and there appears to be an added benefit of using a statin medicine on top of ART to further reduce ongoing comorbidities, which are very common in this group, including cardiovascular disease.”

He continued: “What we tested was adding on a statin to people who are on antiretroviral therapy: those people were having heart attacks and strokes, and we reduced those. . . . In that group we could further add to the effects of antiretroviral therapy to further decrease inflammation and improve traditional risk factors at the same time.”

Of note, he added, rates of statin side effects were similar in REPRIEVE to those seen in the general population.

According to Grinspoon, investigators hope to get their data presented and published as soon as possible.