Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers in HIV
Authors: Lu Michael T. , Ribaudo Heather , Foldyna Borek , Zanni Markella V. , Mayrhofer Thomas , Karady Julia , Taron Jana , Fitch Kathleen V. , McCallum Sara , Burdo Tricia H. , Paradis Kayla , Hedgire Sandeep S. , Meyersohn Nandini M. , DeFilippi Christopher , Malvestutto Carlos D. , Sturniolo Audra , Diggs Marissa , Siminski Sue , Bloomfield Gerald S. , Alston-Smith Beverly , Desvigne-Nickens Patrice , Overton Edgar T. , Currier Judith S. , Aberg Judith A. , Fichtenbaum Carl J. , Hoffmann Udo , Douglas Pamela S. , Grinspoon Steven K. ,   REPRIEVE Trial Writing Group, Fichtenbaum Carl J. , Aberg Judith A. , Daar Eric S. , Taiwo Babafemi , Koletar Susan L. , Chew Kara W. , Little Susan J. , Heath Sonya L. , Jacobson Jeffrey M. , Gandhi Rajesh , Robbins Gregory , Presti Rachel M. , Glesby Marshall , Luetkemeyer Annie , Tebas Pablo , Riddler Sharon A. , Dube Michael P. , Santana-Bagur Jorge L. , Sha Beverly E. , Manne Jennifer , Arduino Roberto , Flexner Charles W. , Haas David W. , Wohl David A. , Sobieszczyk Magdalena E. , Tashima Karen T. , Munsiff Sonal S. , Bender Ignacio Rachel , Marks Kristen , Van Dam Cornelius , Swaminathan Shobha , Campbell Thomas B. , Alston-Smith Beverly , Bandettini Patricia , Bloomfield Gerald , Currier Judith , Desvigne-Nickens Patrice , Diggs Marissa , Douglas Pamela S. , Fitch Kathleen V. , Grinspoon Steven K. , Kim Peter , Lu Michael T. , Paradis Kayla , Ribaudo Heather J. , Rosenberg Yves , Troendle James , Byroads Mark , Gershman Elaine , Lawal Folake , Leon-Cruz Jorge , Louis Rochelle , Lowe Cheryl , Moy Eva , Umbleja Triin , Upadhyay Namrata , Wiviott Stephen , Wood Kenneth , Anthony Oladapo , Barve Radhika , Bone Fred , Bannoo Selina , Duffy Annie , Fletcher Carl , Green Madison , Klop-Packel Nory , McCallum Sara , Norton Emilia , Nowak Jennifer , Sanchez Grande Maria , Siminski Sue , Walker Eloise , Vlieg David , Burdo Tricia , Moran Laura , Roa Jhoanna , Sprenger Heather , Adedeji Bola , Alli Oladapo , Castillo Blanca , Dragavon Joan , Easley Keisha , Falutz Julian , Grzejka Ewelinka , Hoffman Erin , Liao Yuji , Looby Sara , Nohynek Dana , Pate Mary , Rooney James , Shahkolahi Akbar , Sponseller Craig , Williams Kenneth , Zanni Markella , Borloglou Kate , Clement Meredith , Eckard Allison , LeBlanc Rebecca , Malvestutto Carlos , Overton Edgar T , Shaw Karl , Triant Virginia , Kantor Amy , Manne-Goehler Jennifer M. , Starr Kate , Barnett Ronald , Baum Jane , Coates Cindy , Cordoso Sandra W. , Costanza Christie Lyn , Davila Sylvia , Jayaweera Dushyantha , Greenfield Teri , Gutzman Howard , Harden Regina , Henn Sarah , Humphries MJ , Jain Mamta , Klein David , Kohrs Sharon , Lama Javier , Landis Jessica , Leone Jaclyn , Lira Rita , Martinez Maria , Novak Richard , Reese Karen , Santos Breno , Tucker Jenese , Wilkin Aimee , Wilson Tomeka , Foldyna Borek , Karady Julia , Mayrhofer Thomas , Sturniolo Audra , Bastow Barbara , Giguel Francoise , Saleh Nada , Ward John , Cherban Erin , Brummel Sean , Granche Janeway , Moser Carlee , Paczuski Pawel , Smeaton Laura , Benjamin Claire , Cadet Tanisha , Fulda Evelynne , Murphy Jacqueline , Diggs Alicia , Ettinger Robert , Hernandez Angel , Jarrells Janice , Selvage Shirley , Hedgire Sandeep , Hoffman Udo , Meyersohn Nina M. , Taron Jana , Holguin Anthony , Pavlov Gregory , Hammer Scott , Hirsch Martin , Manson JoAnn , Ridker Paul , Stein James , Tracy Russel , Udelson James , Martinez Esteban , Leaver Tim , Pozniak Anton , Melbourne Kathy , Budoff Matthew , Cheng Ben , Goldkind Sara , Grunfeld Carl , Harrington Robert , Lloyd-Jones Donald , Robinson Jennifer , Sleeper Lynn , Sopko George , Volberding Paul , Ketema Fassil , Klingman Karin , Johnson Keisha , Mishkin Mark , Livnat Daniella , Ojumu Akin , Sierto Alba 
Published: February 2024

ImportanceCardiovascular 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.ObjectiveTo 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 ParticipantsThis 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.InterventionOral pitavastatin calcium, 4 mg per day.Main Outcomes and MeasuresCoronary CTA and inflammatory biomarkers at baseline and 24 months. The primary outcomes were change in noncalcified coronary plaque volume and progression of noncalcified plaque.ResultsOf 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 &amp;lt; .001) and lipoprotein-associated phospholipase A2 (−7% [95% CI, −11 to −4] vs 14% [95% CI, 10-18]; P &amp;lt; .001) compared with placebo at 24 months.Conclusions and RelevanceIn 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 RegistrationClinicalTrials.gov Identifier: NCT02344290