Study on Statins Impact on Cardiovascular Prevention in People With HIV Halted

Earlier this year, an international clinical trial testing statin therapy for primary cardiovascular prevention in people living with HIV ended early due to strong evidence of efficacy and safety in the population.

An interim analysis of data from the REPRIEVE study revealed that a daily dose of pitavastatin lowered the risk for major adverse cardiovascular events by 35% compared with placebo, which was sufficiently compelling and warranted the study’s independent data safety and monitoring board to stop the trial early. Pitavastatin is sold under the brand names Livalo ad Zypitamag.

Steven Grinspoon, M.D.

Steven Grinspoon, M.D., professor of medicine at Harvard Medical School and Massachusetts General Hospital, led the study.

It’s been known for a number of years now that patients with HIV have increased risk of cardiovascular disease.

“Over the years, a number of studies have shown that beyond traditional (cardiovascular) risks, there may be other factors including inflammation and residual immune activation in these patients, even those on antiviral therapy that’s functioning,” Grinspoon said. “That’s the reason we wanted to perform the primary cardiovascular prevention trial, because there is an elevated risk and we know those patients don’t typically qualify (for statin therapy).

The REPRIEVE study started in 2015 and enrolled 7,769 adults with HIV, ages 40-75. They were from 12 countries in Asia, Europe, North America, South America, and Africa. All in the study participants were taking antiretroviral therapy, had CD4+ cell counts > 100 cells/mm3 of blood at enrollment, and were at low-to- moderate risk for cardiovascular disease.

Early results showed statin therapy was associated with a reduced risk of heart attacks and strokes and no unanticipated safety concerns. The trial was halted when the data safety and monitoring board determined that the benefits of daily pitavastatin outweighed any risks.

“It was a highly effective and really fantastic result,” Grinspoon said, but adding that starting a patient with HIV on a statin remains an individualized decision.

“Statins have a dual effect. One is to lower LDL [low-density lipoprotein], which is a key driver of cardiovascular disease and it was successful in showing significant lowering of LDL,” he said. “In addition, there are pleotropic effects on other pathways, including inflammatory pathways, and we saw a very robust effect and hypothesized that this is due to not only the LDL effect but effects on these other pathways.”