Steven K Grinspoon1, Kathleen V Fitch2, Edgar Turner Overton3, Carl J Fichtenbaum4, Markella V Zanni2, Judith A Aberg5, Carlos Malvestutto6, Michael T Lu7, Judith S Currier8, Craig A Sponseller9, Myron Waclawiw10, Beverly Alston-Smith11, Katharine Cooper-Arnold10, Karin L Klingman11, Patrice Desvigne-Nickens10, Udo Hoffmann7, Heather J Ribaudo12, Pamela S Douglas13. 1. MGH Program in Nutritional Metabolism and Harvard Medical School, Boston, MA. Electronic address: sgrinspoon@mgh.harvard.edu. 2. MGH Program in Nutritional Metabolism and Harvard Medical School, Boston, MA. 3. Division of Infectious Diseases, University of Alabama at Birmingham School of Medicine, Birmingham, AL. 4. Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH. 5. Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. 6. Division of Infectious Diseases, Ohio State University Wexner Medical Center, Columbus, OH. 7. Cardiac MR PET CT Program and Department of Radiology, Massachusetts General Hospital, Boston, MA. 8. David Geffen School of Medicine at University of California Los Angeles, Division of Infectious Diseases, Los Angeles, CA. 9. Kowa Pharmaceuticals America, Inc., Montgomery, AL. 10. National Institutes of Health/National Heart, Lung, and Blood Institute, Bethesda, MD. 11. DAIDS, NIAID, NIH, Bethesda, MD. 12. Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA. 13. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
Abstract
BACKGROUND:Cardiovascular disease (CVD) is more frequent among people with HIV (PWH) and may relate to traditional and nontraditional factors, including inflammation and immune activation. A critical need exists to develop effective strategies to prevent CVD in this population. METHODS: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) (A5332) is a prospective, randomized, placebo-controlled trial of a statin strategy for the primary prevention of major adverse cardiovascular events (MACE) in PWH with low to moderate traditional risk. At least 7,500 PWH, 40-75 years of age, on stable antiretroviral therapy, will be randomized to pitavastatin calcium (4 mg/d) or identical placebo and followed for up to 8 years. Participants are enrolled based on the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk score and low-density lipoprotein cholesterol (LDL-C) level with a goal to identify a low- to moderate-risk population who might benefit from a pharmacologic CVD prevention strategy. Potential participants with a risk score ≤ 15% were eligible based on decreasing LDL-C thresholds for increasing risk score >7.5% (LDL-C <190 mg/dL for risk score <7.5%, LDL-C <160 mg/dL for risk score 7.6%-10%, and LDL-C<130 mg/dL for risk score 10.1%-15%). The primary objective is to determine effects on a composite end point of MACE. Formal and independent adjudication of clinical events will occur using standardized criteria. Key secondary end points include effects on MACE components, all-cause mortality, specified non-CVD events, AIDS and non-AIDS events, and safety. RESULTS: To date, REPRIEVE has enrolled >7,500 participants at approximately 120 sites across 11 countries, generating a diverse and representative population of PWH to investigate the primary objective of the trial. CONCLUSIONS: REPRIEVE is the first trial investigating a primary CVD prevention strategy in PWH. REPRIEVE will inform the field of the efficacy and safety of a statin strategy among HIV-infected participants on antiretroviral therapy and provide critical information on CVD mechanisms and non-CVD events in PWH.
RCT Entities:
BACKGROUND:Cardiovascular disease (CVD) is more frequent among people with HIV (PWH) and may relate to traditional and nontraditional factors, including inflammation and immune activation. A critical need exists to develop effective strategies to prevent CVD in this population. METHODS: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) (A5332) is a prospective, randomized, placebo-controlled trial of a statin strategy for the primary prevention of major adverse cardiovascular events (MACE) in PWH with low to moderate traditional risk. At least 7,500 PWH, 40-75 years of age, on stable antiretroviral therapy, will be randomized to pitavastatin calcium (4 mg/d) or identical placebo and followed for up to 8 years. Participants are enrolled based on the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk score and low-density lipoprotein cholesterol (LDL-C) level with a goal to identify a low- to moderate-risk population who might benefit from a pharmacologic CVD prevention strategy. Potential participants with a risk score ≤ 15% were eligible based on decreasing LDL-C thresholds for increasing risk score >7.5% (LDL-C <190 mg/dL for risk score <7.5%, LDL-C <160 mg/dL for risk score 7.6%-10%, and LDL-C<130 mg/dL for risk score 10.1%-15%). The primary objective is to determine effects on a composite end point of MACE. Formal and independent adjudication of clinical events will occur using standardized criteria. Key secondary end points include effects on MACE components, all-cause mortality, specified non-CVD events, AIDS and non-AIDS events, and safety. RESULTS: To date, REPRIEVE has enrolled >7,500 participants at approximately 120 sites across 11 countries, generating a diverse and representative population of PWH to investigate the primary objective of the trial. CONCLUSIONS: REPRIEVE is the first trial investigating a primary CVD prevention strategy in PWH. REPRIEVE will inform the field of the efficacy and safety of a statin strategy among HIV-infectedparticipants on antiretroviral therapy and provide critical information on CVD mechanisms and non-CVD events in PWH.
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