CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

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Plaque, Inflammation, Subclinical Myocardial Injury, and MACE in the REPRIEVE Mechanistic Substudy Michael T. Lu 1 , Sara McCallum 1 , Heather Ribaudo 2 , Markella V. Zanni 1 , Christopher R. Defilippi 3 , Jana Taron 1 , Julia Karady 1 , Borek Foldyna 1 , Sarah Chu 1 , Carl Fichtenbaum 4 , Carlos Malvestutto 5 , Judith Aberg 6 , Thomas Mayrhofer 1 , Pamela Douglas 7 , Steven Grinspoon 1 , for the REPRIEVE Study Team 1 Massachusetts General Hospital, Boston, MA, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 Inova Juniper Program, Fairfax, VA, USA, 4 University of Cincinnati Medical Center, Cincinnati, OH, USA, 5 The Ohio State University, Columbus, OH, USA, 6 Icahn School of Medicine at

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Frailty Is Associated With Higher MACE Incidence but Does Not Appear to Modify Pitavastatin Effects Kristine M. Erlandson 1 , Ariela R. Orkaby 2 , Triin Umbleja 3 , Heather Ribaudo 3 , Todd Brown 4 , Kathleen V. Fitch 5 , Carlos Malvestutto 6 , Karen T. Tashima 7 , Marcus V. G. Lacerda 8 , Sonya L. Heath 9 , Alan Landay 10 , George A. Kuchel 11 , Pamela Douglas 12 ,

Oral Abstracts

Mount Sinai, New York, NY, USA, 7 Duke Clinical Research Institute, Durham, NC, USA Background: REPRIEVE established that pitavastatin prevents major adverse cardiovascular events (MACE) and reduces noncalcified coronary plaque (NCP) on coronary CT angiography, in low-moderate risk PWH. We leveraged the REPRIEVE Mechanistic Substudy to assess for the first time the relationship of coronary plaque and indices of inflammation and subclinical myocardial injury with MACE and the effects of pitavastatin on MACE. Methods: REPRIEVE Mechanistic Substudy participants (N=804) enrolled from April 2015 to February 2018 at 31 US sites, randomized to pitavastatin 4 mg/day or placebo, were followed for incident MACE over median 5.9 yrs. We assessed the relationship of baseline NCP (n=755), markers of inflammation (hs-CRP, IL-6, and LpPLA-2) (n=790), as well as markers of subclinical myocardial injury (hs-cTnT) (n=750) with MACE and the modification of the statin effect by these parameters, using Cox proportional hazards models stratified by statin randomization. Results: Of enrolled participants (17% female, 47% non-White, median age 51 yrs, LDL 105 mg/dL, 10-year cardiovascular risk 4.6%), MACE incidence was 7.26/1000 person-years (17 events) for pitavastatin and 9.15/1000 person-years (21 events) for placebo. 40% (302/755) of participants had NCP at baseline. NCP was present in 62% (23/37) of those with MACE compared to 39% (279/718) without MACE. The risk of MACE was greater in those with NCP vs. without (HR 2.5, [CI 1.3, 4.8], P=0.008 (Figure)). Elevated levels of hs-CRP (P=0.049) and hs-cTnT (P=0.003) and higher IL-6 (P=0.033) at study entry were associated with MACE (Figure). These trends persisted after adjusting for ASCVD risk. The effect of pitavastatin to reduce MACE was higher in those with NCP (HR 0.56 (0.24, 1.31) vs. those without 1.28 (0.44, 3.68)). Likewise, a greater effect of pitavastatin was observed in those with elevated hs-cTnT (>7.5ng/L) vs. those without (HR 0.68 (0.30, 1.53) vs. 1.66 (0.40, 6.93)). However, confidence intervals overlapped given the small number of events in the substudy. Conclusions: NCP and higher hs-cTnT, hs-CRP, and IL-6 are associated with MACE in asymptomatic low-moderate risk PWH. This analysis suggests that the benefit of pitavastatin to prevent MACE may be greater in persons with preexisting plaque and baseline levels of subclinical myocardial injury. Further investigation is needed to determine whether plaque and/or biomarkers can help identify PWH at highest risk who would most benefit from statin prevention.

Steven Grinspoon 5 , for the REPRIEVE Study Team 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 Brigham and Women's Hospital, Boston, MA, USA, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 5 Massachusetts General Hospital, Boston, MA, USA, 6 The Ohio State University, Columbus, OH, USA, 7 Brown University, Providence, RI, USA, 8 Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil, 9 University of Alabama at Birmingham, Birmingham, AL, USA, 10 University of Texas Medical Branch, Galveston, TX, USA, 11 University of Connecticut Health Center, Farmington, CT, USA, 12 Duke Clinical Research Institute, Durham, NC, USA Background: People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular diseases (ASCVD) and accelerated aging, including frailty. REPRIEVE demonstrated a 36% reduction in the hazard of major adverse cardiovascular events (MACE) for pitavastatin vs placebo among PWH, but little is known about statins for ASCVD prevention among PWH with frailty. The goal of this post-hoc analysis was to examine whether frailty is associated with MACE among PWH, and whether statins prevent MACE across a spectrum of frailty. Methods: REPRIEVE randomized PWH aged 40-75 without ASCVD to pitavastatin 4mg vs placebo. Frailty was measured with a 32-item cumulative deficit frailty index (FI) and classified as non-frail (<0.1), pre-frail (0.1-0.2) and frail (>0.2-1) using Rockwood approach. Cox proportional hazards models were used to estimate cause-specific hazard ratio (HR) of MACE by frailty status, stratified by treatment group. Modification of pitavastatin effect by frailty was assessed via interaction with treatment. Fractional polynomials were used to evaluate pitavastatin effect continuously across the FI. Results: Of 7769 REPRIEVE participants, 7740 (>99%) had sufficient data to calculate FI at study entry. Median age was 50 years (Q1, Q3: 45, 55), ASCVD risk score 4.5 (2.1, 7.0)%, 31% were female, and 65% non-White. FI ranged from 0 to 0.44, with 68% classified as non-frail, 28% pre-frail and 4% frail. Frailty status showed good predictive validity for mortality: adjusted for age and sex, HR of death was 1.63 (95% CI: 1.27, 2.09) among pre-frail, 1.47 (95% CI: 0.83, 2.60) among frail compared to non-frail participants (p=0.0005 for overall effect of frailty status). Over median 5.6 years of follow up, MACE incidence rate (IR) was 4.51/1000 person-years (PY) among non-frail, 9.88/1000PY among pre-frail, and 14.39 among frail participants (HR=1.72 among pre-frail, and 2.15 among frail compared to non-frail, adjusted for age, sex and ASCVD risk score; p<0.0001, Figure panel A). There was no evidence that pitavastatin effect differed by frailty status (p=0.39; Figure panel B), but with uncertainty in the frail category due to small numbers. Further analysis using continuous FI suggested consistent pitavastatin effect across the spectrum of frailty.

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CROI 2025