Frailty, Pitavastatin, and Major Adverse Cardiovascular Events Among People With HIV

Background: People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular diseases (ASCVDs) and geriatric syndromes, including frailty. REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) demonstrated a 36% reduction in major adverse cardiovascular events (MACE) with pitav...

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Main Authors: Kristine M. Erlandson, MD, MS, Ariela R. Orkaby, MD, Triin Umbleja, MSc, Heather J. Ribaudo, PhD, Todd T. Brown, MD, PhD, Markella V. Zanni, MD, Marissa R. Diggs, AB, Sarah M. Chu, MSN, Kathleen V. Fitch, MSN, Carl J. Fichtenbaum, MD, Carlos Malvestutto, MD, MPH, Judith A. Aberg, MD, Gerald S. Bloomfield, MD, MPH, Judith S. Currier, MD, Karen T. Tashima, MD, Marcus Vinícius Guimarães de Lacerda, MD, PhD, Sonya L. Heath, MD, Michael T. Lu, MD, MPH, Alan Landay, PhD, George A. Kuchel, MD, Pamela S. Douglas, MD, Steven K. Grinspoon, MD
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:JACC: Advances
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772963X25005022
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author Kristine M. Erlandson, MD, MS
Ariela R. Orkaby, MD
Triin Umbleja, MSc
Heather J. Ribaudo, PhD
Todd T. Brown, MD, PhD
Markella V. Zanni, MD
Marissa R. Diggs, AB
Sarah M. Chu, MSN
Kathleen V. Fitch, MSN
Carl J. Fichtenbaum, MD
Carlos Malvestutto, MD, MPH
Judith A. Aberg, MD
Gerald S. Bloomfield, MD, MPH
Judith S. Currier, MD
Karen T. Tashima, MD
Marcus Vinícius Guimarães de Lacerda, MD, PhD
Sonya L. Heath, MD
Michael T. Lu, MD, MPH
Alan Landay, PhD
George A. Kuchel, MD
Pamela S. Douglas, MD
Steven K. Grinspoon, MD
author_facet Kristine M. Erlandson, MD, MS
Ariela R. Orkaby, MD
Triin Umbleja, MSc
Heather J. Ribaudo, PhD
Todd T. Brown, MD, PhD
Markella V. Zanni, MD
Marissa R. Diggs, AB
Sarah M. Chu, MSN
Kathleen V. Fitch, MSN
Carl J. Fichtenbaum, MD
Carlos Malvestutto, MD, MPH
Judith A. Aberg, MD
Gerald S. Bloomfield, MD, MPH
Judith S. Currier, MD
Karen T. Tashima, MD
Marcus Vinícius Guimarães de Lacerda, MD, PhD
Sonya L. Heath, MD
Michael T. Lu, MD, MPH
Alan Landay, PhD
George A. Kuchel, MD
Pamela S. Douglas, MD
Steven K. Grinspoon, MD
author_sort Kristine M. Erlandson, MD, MS
collection DOAJ
description Background: People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular diseases (ASCVDs) and geriatric syndromes, including frailty. REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) demonstrated a 36% reduction in major adverse cardiovascular events (MACE) with pitavastatin vs placebo but the role of statins for ASCVD prevention among frail PWH is not known. Objectives: The purpose of this study was to evaluate whether frailty is associated with MACE and whether pitavastatin prevents MACE regardless of frailty. Methods: We conducted a post hoc analysis of the REPRIEVE trial, a randomized, blinded trial of pitavastatin 4 mg vs placebo. Participants included PWH without ASCVD, aged 40 to 75 years. Frailty was measured with a 32-item frailty index. Cox proportional hazards models were used to estimate cause-specific hazard of MACE by frailty status. Pitavastatin effect modification by frailty status was assessed via interaction with treatment. Results: Of 7769 REPRIEVE participants, 7,740 (>99%) had sufficient data to calculate frailty index. Median age was 50 years (Q1, Q3: 45, 55), 67% were nonfrail, 29% prefrail, and 4% frail at baseline; median follow-up was 5.6 years. Adjusted for age, sex, ASCVD risk score, and treatment group, MACE hazard increased with frailty (P < 0.0001): HR: 1.76 (95% CI: 1.35-2.30) among prefrail, and 2.14 (95% CI: 1.33-3.45) among frail compared to nonfrail. There was no evidence that pitavastatin effect differed by frailty status (P = 0.44). Conclusions: Frailty was associated with markedly higher hazard of MACE. Though frailty did not appear to modify the protective effects of pitavastatin seen in the primary trial, the efficacy in frail PWH remains uncertain due to the limited number of frail individuals.
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spelling doaj-art-491fba4e3061436dafbbe8efe0f5038d2025-08-22T04:58:59ZengElsevierJACC: Advances2772-963X2025-09-014910207710.1016/j.jacadv.2025.102077Frailty, Pitavastatin, and Major Adverse Cardiovascular Events Among People With HIVKristine M. Erlandson, MD, MS0Ariela R. Orkaby, MD1Triin Umbleja, MSc2Heather J. Ribaudo, PhD3Todd T. Brown, MD, PhD4Markella V. Zanni, MD5Marissa R. Diggs, AB6Sarah M. Chu, MSN7Kathleen V. Fitch, MSN8Carl J. Fichtenbaum, MD9Carlos Malvestutto, MD, MPH10Judith A. Aberg, MD11Gerald S. Bloomfield, MD, MPH12Judith S. Currier, MD13Karen T. Tashima, MD14Marcus Vinícius Guimarães de Lacerda, MD, PhD15Sonya L. Heath, MD16Michael T. Lu, MD, MPH17Alan Landay, PhD18George A. Kuchel, MD19Pamela S. Douglas, MD20Steven K. Grinspoon, MD21Department of Medicine, University of Colorado Denver- Anschutz Medical Campus, Aurora, Colorado, USA; Address for correspondence: Dr Kristine M. Erlandson, University of Colorado Anschutz Medical Campus, 12700 E. 19th Avenue, Mail Stop B168 Aurora, Colorado 80045, USA.New England GRECC (Geriatric Research, Education, and Clinical Center), VA Boston Healthcare System, Boston, Massachusetts, USA; Division of Aging, Department of Medicine, Brigham &amp; Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USADepartment of Biostatistics, Harvard TH Chan School of Public Health, Boston, Massachusetts, USADepartment of Biostatistics, Harvard TH Chan School of Public Health, Boston, Massachusetts, USADepartment of Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USAMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USAMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USAMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USAMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USADepartment of Medicine, Ohio State University Medical Center, Columbus, Ohio, USADepartment of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USADuke Clinical Research Institute, Duke Global Health Institute and Department of Medicine, Duke University, Durham, North Carolina, USADepartment of Medicine, University of California Los Angeles, Los Angeles, California, USADepartment of Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USAFundação de Medicina Tropical Dr Heitor Vieira Dourado and Fiocruz, Manaus, BrazilDepartment of Medicine, University of Alabama Birmingham School of Medicine, Birmingham, Alabama, USACardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, University of Texas Galveston Branch, Galveston, Texas, USADepartment of Medicine, University of Connecticut, Farmington, Connecticut, USADuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USADepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USABackground: People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular diseases (ASCVDs) and geriatric syndromes, including frailty. REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) demonstrated a 36% reduction in major adverse cardiovascular events (MACE) with pitavastatin vs placebo but the role of statins for ASCVD prevention among frail PWH is not known. Objectives: The purpose of this study was to evaluate whether frailty is associated with MACE and whether pitavastatin prevents MACE regardless of frailty. Methods: We conducted a post hoc analysis of the REPRIEVE trial, a randomized, blinded trial of pitavastatin 4 mg vs placebo. Participants included PWH without ASCVD, aged 40 to 75 years. Frailty was measured with a 32-item frailty index. Cox proportional hazards models were used to estimate cause-specific hazard of MACE by frailty status. Pitavastatin effect modification by frailty status was assessed via interaction with treatment. Results: Of 7769 REPRIEVE participants, 7,740 (>99%) had sufficient data to calculate frailty index. Median age was 50 years (Q1, Q3: 45, 55), 67% were nonfrail, 29% prefrail, and 4% frail at baseline; median follow-up was 5.6 years. Adjusted for age, sex, ASCVD risk score, and treatment group, MACE hazard increased with frailty (P < 0.0001): HR: 1.76 (95% CI: 1.35-2.30) among prefrail, and 2.14 (95% CI: 1.33-3.45) among frail compared to nonfrail. There was no evidence that pitavastatin effect differed by frailty status (P = 0.44). Conclusions: Frailty was associated with markedly higher hazard of MACE. Though frailty did not appear to modify the protective effects of pitavastatin seen in the primary trial, the efficacy in frail PWH remains uncertain due to the limited number of frail individuals.http://www.sciencedirect.com/science/article/pii/S2772963X25005022frailtyHIVmajor adverse cardiovascular eventstatin
spellingShingle Kristine M. Erlandson, MD, MS
Ariela R. Orkaby, MD
Triin Umbleja, MSc
Heather J. Ribaudo, PhD
Todd T. Brown, MD, PhD
Markella V. Zanni, MD
Marissa R. Diggs, AB
Sarah M. Chu, MSN
Kathleen V. Fitch, MSN
Carl J. Fichtenbaum, MD
Carlos Malvestutto, MD, MPH
Judith A. Aberg, MD
Gerald S. Bloomfield, MD, MPH
Judith S. Currier, MD
Karen T. Tashima, MD
Marcus Vinícius Guimarães de Lacerda, MD, PhD
Sonya L. Heath, MD
Michael T. Lu, MD, MPH
Alan Landay, PhD
George A. Kuchel, MD
Pamela S. Douglas, MD
Steven K. Grinspoon, MD
Frailty, Pitavastatin, and Major Adverse Cardiovascular Events Among People With HIV
JACC: Advances
frailty
HIV
major adverse cardiovascular event
statin
title Frailty, Pitavastatin, and Major Adverse Cardiovascular Events Among People With HIV
title_full Frailty, Pitavastatin, and Major Adverse Cardiovascular Events Among People With HIV
title_fullStr Frailty, Pitavastatin, and Major Adverse Cardiovascular Events Among People With HIV
title_full_unstemmed Frailty, Pitavastatin, and Major Adverse Cardiovascular Events Among People With HIV
title_short Frailty, Pitavastatin, and Major Adverse Cardiovascular Events Among People With HIV
title_sort frailty pitavastatin and major adverse cardiovascular events among people with hiv
topic frailty
HIV
major adverse cardiovascular event
statin
url http://www.sciencedirect.com/science/article/pii/S2772963X25005022
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