Statin cuts CV risk in patients with HIV
Treatment with pitavastatin is associated with a significantly lower risk of cardiovascular (CV) events in people living with human immunodeficiency virus (HIV) as shown in the final analysis of the double-blind, placebo-controlled REPRIEVE trial presented at IAS 2023.
“There was a significant 35 percent lower risk of major adverse cardiovascular events (MACE) with pitavastatin after a median follow-up of 5.1 years,” reported Dr Steven Grinspoon from Massachusetts General Hospital and Harvard Medical School in Boston, Massachusetts, US.
The results are important as HIV infection is an independent risk factor for cardiovascular disease (CVD), he pointed out. “People with HIV have double the risk of myocardial infarction (MI) and stroke than the general population.”
Often, these people are younger without high cholesterol and other risk factors, and would not be recommended for statin therapy. Primary prevention strategies are therefore warranted in this population, emphasized Grinspoon.
Pitavastatin over 5.1 years
REPRIEVE included 7,769 adults from 12 countries in Asia, Europe, North America, South America, and Africa with HIV infection who were taking antiretroviral therapy. They had a median CD4+ cell count of 621 cells/mm3 at enrolment. Over 87 percent had an HIV viral load below the lower limit of quantification. The median 10-year Atherosclerotic Cardiovascular Disease risk score was 4.5 percent. The median age was 50 years.
“These are people who, if they come to the doctor’s office, would be told their risk score does not make them eligible for a statin,” Grinspoon said.
All were randomly assigned to pitavastatin calcium 4 mg daily or placebo. The primary outcome of the study was the occurrence of major adverse cardiovascular events (MACE), defined as a composite of CV death, stroke, MI, hospitalization for unstable angina, transient ischaemic attack, peripheral arterial ischaemia, revascularization, or death from an undetermined cause.
The trial was stopped early for efficacy after a median follow-up of 5.1 years. The incidence of MACE was 4.81 per 1,000 person-years with pitavastatin vs 7.32 per 1,000 person-years with placebo (hazard ratio [HR], 0.65; p=0.002).
Muscle pain and weakness occurred in 91 patients (2.3 percent) on pitavastatin and in 53 (1.4 percent) on placebo, but the majority were low-grade. Diabetes developed in 206 (5.3 percent) and 155 patients (4 percent), respectively.
“What is interesting is that the reduction in risk was nearly twice as what we would expect in an LDL-lowering drug, based on what we’ve seen from previous statin trials in non-HIV-positive populations,” Grinspoon said. “The benefit could be partly due to the LDL reduction.”
An individualized decision
“Starting HIV patients on a statin remains an individualized decision,” said Grinspoon. “Our study suggests a clear benefit in this population. REPRIEVE is important because there are limited existing interventions to help prevent adverse CV outcomes in HIV patients.”
Meanwhile, a subanalysis of REPRIEVE focusing on women alone found that they have higher levels of inflammatory markers (IL-6, C-reactive protein, and D-dimer) but lower prevalence of coronary artery plaques compared with men.
“Our finding represents an interesting paradox given that high levels of these inflammatory markers have been associated with coronary artery plaque, both among women and men living with HIV,” said Dr Markella Zanni from Massachusetts General Hospital in Boston, Massachusetts, US. She added that heart risk is something women with HIV should discuss with their treating physician, to include potential prevention strategies, including statin therapy on top of healthy lifestyle changes.