Originally published by our sister publication Pharmacy Practice News
Statins may offset the high risk for cardiovascular disease (CVD) in people living with HIV by more than one-third, potentially preventing one in five major CV events or premature deaths in this high-risk group (N Engl J Med 2023 July 23. doi:10.1056/NEJMoa2304146).
The risk for CVD in people living with HIV can be 50% to 100% greater than those without HIV, according to results that also were presented at the IAS 2023 Conference on HIV Science, held in Brisbane, Australia.
“It has been known that HIV itself is a potent cardiovascular risk factor, probably through inflammatory derangement,” said C. Michael White, PharmD, FCP, FCCP, the department head and a distinguished professor of pharmacy practice at the UConn School of Pharmacy, in Storrs.
“Some HIV treatments can reduce HIV levels attenuating that risk, but they elevate LDL levels. As such, the LDL and C-reactive protein reductions associated with statins do culminate in ASCVD [atherosclerotic cardiovascular disease] event reductions,” said Dr. White, a cardiovascular expert, who was not part of the trial but was asked to comment on the results.
For the double-blind, phase 3 REPRIEVE (Randomized Trial to Prevent Events in HIV) trial, researchers randomly selected 7,769 participants between 40 and 75 years of age to receive daily pitavastatin calcium or placebo. REPRIEVE began in 2015. The participants were enrolled from 145 sites in 12 countries.
Adults in the study were an average age of 50 and had a low to moderate risk for CVD, so they normally would not have been prescribed statins. Women accounted for 31% of participants. Approximately 41% of study participants identified as Black, 35% as white, 15% as Asian and 9% as another race.
The fact that the study was done in a diverse population was a positive, Dr. White said. “I appreciate the racial and sex diversity in this trial with strong evidence of benefit across different groups.”
To understand the benefits, the researchers compared how often participants in each group experienced a major CV event, including myocardial infarction, stroke or angioplasty. Participants who took daily pitavastatin had 35% fewer major CV events than those who received placebo. The researchers also measured the number of deaths in combination with major CV events during the study and found participants in the treatment group were 21% less likely than those in the placebo group to experience these events. Additionally, those who took pitavastatin had a 30% reduction in their low-density lipoprotein (LDL) cholesterol levels.
The researchers followed participants for about five years, but ended the trial early when they discovered the treatment benefits outweighed potential risks.
Additional Statin Effects
“Lowering LDL cholesterol levels reduces risks for cardiovascular events, like having a heart attack and stroke, but these findings suggest there may be additional effects of statin therapy that explain these reduced risks among people living with HIV,” said Steven K. Grinspoon, MD, the study chair, who is also chief of the metabolism unit at Massachusetts General Hospital, in Boston. “Ongoing research about how statin therapy may affect inflammation and increased immune activation among people with HIV may help us better understand the additional benefits we’re seeing with this treatment approach.”
To support optimal health outcomes among the study participants, researchers required those who enrolled to have normal liver and kidney function. They were also required to be on antiretroviral therapy, which itself is critical to reducing the risk for HIV complications and related comorbidities, including CVD.
The researchers noted more studies are necessary to determine how these results will affect guidelines for the care of people living with HIV.
“Our goal with REPRIEVE was to validate an intervention to improve the lives of people with HIV,” said Hugh Auchincloss, MD, the acting director of the National Institute of Allergy and Infectious Diseases (NIAID), the study sponsor. “This study, supported by thousands of participants and researchers, represented a global recognition that as HIV management has grown more successful, we also need to address the comorbidities such as cardiovascular diseases that afflict people with HIV.”
According to the World Health Organization, more than 38 million people worldwide live with HIV. About 1.5 million new HIV cases were diagnosed in 2021.
“This research suggests that statins may provide an accessible, cost-effective measure to improve the cardiovascular health and quality of life for people living with HIV,” said Gary J. Gibbons, MD, the director of the National Heart, Lung, and Blood Institute (NHLBI), a study funder. “Additional research can further expand on this effect, while providing a road map to rapidly translate research findings into clinical practice.”
Dr. White, a member of the editorial advisory board of Pharmacy Practice News, said he was pleased with the REPRIEVE trial results. “I have been waiting for [these data] for several years,” he said. “While I strongly suspected that LDL lowering in HIV patients would similarly lower atherosclerotic cardiovascular disease, it is wonderful to see proof of that in a major randomized controlled trial.”
The REPRIEVE study was partially funded through grants from NHLBI and NIAID.