Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers in HIV: Mechanistic Substudy of the REPRIEVE Randomized Clinical Trial.

Autor:	Lu MT; Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston., Ribaudo H; Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts., Foldyna B; Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston., Zanni MV; Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston., Mayrhofer T; Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston.; School of Business Studies, Stralsund University of Applied Sciences, Stralsund, Germany., Karady J; Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston.; Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary., Taron J; Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston.; Department of Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Fitch KV; Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston., McCallum S; Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston., Burdo TH; Department of Microbiology, Immunology, and Inflammation, Center for NeuroVirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania., Paradis K; Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston., Hedgire SS; Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston., Meyersohn NM; Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston., DeFilippi C; Inova Heart and Vascular Institute, Falls Church, Virginia., Malvestutto CD; Division of Infectious Diseases, Ohio State University Medical Center, Columbus., Sturniolo A; Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston., Diggs M; Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston., Siminski S; Frontier Science Foundation, Amherst, New York., Bloomfield GS; Department of Medicine, Duke Global Health Institute, Duke Clinical Research Institute, Duke University, Durham, North Carolina., Alston-Smith B; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland., Desvigne-Nickens P; Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland., Overton ET; Division of Infectious Diseases, University of Alabama at Birmingham.; ViiV Healthcare, Research Triangle Park, North Carolina., Currier JS; Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles., Aberg JA; Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York., Fichtenbaum CJ; Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio., Hoffmann U; Cleerly, Denver, Colorado., Douglas PS; Duke University Research Institute, Duke University School of Medicine, Durham, North Carolina., Grinspoon SK; Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston.
Jazyk:	angličtina
Zdroj:	JAMA cardiology [JAMA Cardiol] 2024 Apr 01; Vol. 9 (4), pp. 323-334.
DOI:	10.1001/jamacardio.2023.5661
Abstrakt:	Importance: Cardiovascular disease (CVD) is increased in people with HIV (PWH) and is characterized by premature noncalcified coronary plaque. In the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), pitavastatin reduced major adverse cardiovascular events (MACE) by 35% over a median of 5.1 years. Objective: To investigate the effects of pitavastatin on noncalcified coronary artery plaque by coronary computed tomography angiography (CTA) and on inflammatory biomarkers as potential mechanisms for MACE prevention. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial enrolled participants from April 2015 to February 2018 at 31 US clinical research sites. PWH without known CVD who were taking antiretroviral therapy and had low to moderate 10-year CVD risk were included. Data were analyzed from April to November 2023. Intervention: Oral pitavastatin calcium, 4 mg per day. Main Outcomes and Measures: Coronary CTA and inflammatory biomarkers at baseline and 24 months. The primary outcomes were change in noncalcified coronary plaque volume and progression of noncalcified plaque. Results: Of 804 enrolled persons, 774 had at least 1 evaluable CTA. Plaque changes were assessed in 611 who completed both CT scans. Of 611 analyzed participants, 513 (84.0%) were male, the mean (SD) age was 51 (6) years, and the median (IQR) 10-year CVD risk was 4.5% (2.6-7.0). A total of 302 were included in the pitavastatin arm and 309 in the placebo arm. The mean noncalcified plaque volume decreased with pitavastatin compared with placebo (mean [SD] change, -1.7 [25.2] mm3 vs 2.6 [27.1] mm3; baseline adjusted difference, -4.3 mm3; 95% CI, -8.6 to -0.1; P = .04; 7% [95% CI, 1-12] greater reduction relative to placebo). A larger effect size was seen among the subgroup with plaque at baseline (-8.8 mm3 [95% CI, -17.9 to 0.4]). Progression of noncalcified plaque was 33% less likely with pitavastatin compared with placebo (relative risk, 0.67; 95% CI, 0.52-0.88; P = .003). Compared with placebo, the mean low-density lipoprotein cholesterol decreased with pitavastatin (mean change: pitavastatin, -28.5 mg/dL; 95% CI, -31.9 to -25.1; placebo, -0.8; 95% CI, -3.8 to 2.2). The pitavastatin arm had a reduction in both oxidized low-density lipoprotein (-29% [95% CI, -32 to -26] vs -13% [95% CI, -17 to -9]; P < .001) and lipoprotein-associated phospholipase A2 (-7% [95% CI, -11 to -4] vs 14% [95% CI, 10-18]; P < .001) compared with placebo at 24 months. Conclusions and Relevance: In PWH at low to moderate CVD risk, 24 months of pitavastatin reduced noncalcified plaque volume and progression as well as markers of lipid oxidation and arterial inflammation. These changes may contribute to the observed MACE reduction in REPRIEVE. Trial Registration: ClinicalTrials.gov Identifier: NCT02344290.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu