Daily statin is game changer for heart disease prevention in people living with HIV
Presenter: Steven Grinspoon, MD, Harvard Medical School, Boston
Key REPRIEVE results and the utility of statins among people living with HIV: what have we learned. Presented July 24, 2023.
Among people 40 to 75 years old living with HIV, on antiretroviral therapy (ART), and at low to moderate risk of a major adverse cardiovascular event (MACE), treatment with pitavatstatin is safe and prevents MACE, according to the primary analysis of the Randomized Trial to Prevent Vascular Events (REPRIEVE) study. The reduction in MACE is independent of baseline low-density lipoprotein cholesterol (LDL-C) level.
The prevalence of cardiovascular disease is increasing in people living with HIV, even as the prevalence is decreasing in the general population. Residual immune activation persists with ART, even with adequate viral suppression. Statins lower both the level of LDL-C and also residual immune activation and inflammation, including in people with HIV, said presenter Steven Grinspoon, MD, Harvard Medical School, Boston. “ART alone is not sufficient to prevent cardiovascular disease,” he said.
Participants in REPRIEVE were recruited from across the globe. Eligible participants were age 40 to 75 years, had documented HIV, were receiving stable ART, and had no known atherosclerotic cardiovascular disease. A total of 7,769 participants were enrolled and were equally randomized to pitavastatin or placebo. Pitavastatin was chosen for the study because it has little interaction with ART, he said.
The study population was diverse: Black/African Americans constituted 41% of those enrolled, and 31% of the total were women. The 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk score required for entry depended on baseline LDL-C level; the higher the ASCVD risk score, the lower the LDL-C level required for equipoise. The median ASCVD risk score was 4.5%. “This is a very low predictive risk; not a typical population for whom you would envision statin therapy,” he said.
More than 80% of participants in each arm remained in follow-up and adherence was “very good to excellent,” said Dr. Grinspoon. The rate of adverse event-related discontinuation was 2% in the pitavastatin arm versus 1% in the placebo arm. “Clinical initiation of a non-study statin occurred in 5.7% of pitavastatin-treated and 9.6% of placebo-treated participants, below threshold of concern,” he added.
The study was terminated early, with a median duration of follow-up of 5.1 years, after demonstrating a clear beneficial effect of pitavastatin. Pitavastatin versus placebo led to a 35% reduction in the incidence of MACE and a 21% reduction in the occurrence of MACE or death. The findings in favor of the pitavastatin were consistent across all of the MACE subcomponents, including first cardiac ischemia or myocardial infarction, first stroke or transient ischemic attack, first peripheral arterial ischemia, cardiovascular death or undetermined cause of death, first cardiac catheterization or revascularization, first carotid or cerebrovascular revascularization, and first peripheral arterial revascularization.
“The effect was robust controlling for ASCVD score and other factors, including age, race, smoking, hypertension, LDL-C level, nadir CD4 count, total ART duration, and GBD (global burden of disease) region as covariates,” he said. The effect size was similar regardless of LDL-C level at enrollment and between men and women, he noted. The effect size was larger than anticipated based on the 30% lowering of LDL-C achieved in the trial.
The number needed to treat (NNT) to prevent 1 MACE event was 106, which compares favorably to aspirin and other preventive approaches such as antihypertensive therapy. The NNT was 35 in those participants with a baseline ASCVD risk score greater than 10%, and 53 in those considered at moderate risk (ASCVD score of 5% to 10%).
Rates of serious adverse events were similar in each group (incidence rate ratio 1.02, 95% confidence interval 0.92–1.14). The rate of muscle-related symptoms was higher in the pitavastatin group but these were mostly mild and only 1% of participants withdrew because of muscle-related symptoms. The rate of diabetes was increased in the pitavastatin group versus placebo (5.3% vs 4.0%), “but this increase was consistent with that seen in prior statin studies, was not significantly above rates demonstrated for the general population, and very few withdrew due to diabetes,” he said.
“Statin therapy with lifestyle counseling should be considered for people with HIV, even those with low to moderate risk,” he concluded. Consideration should also be given to expanding treatment guidelines to include a statin in this patient population.
Dr. Grinspoon reports research funding from the National Institutes of Health, Kowa Pharmaceuticals, Gilead Sciences, ViiV Healthcare and serves as consultant to Theratechnologies and as a consultant to and on the scientific advisory board of Marathon Asset Management