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. 2019 Jun:212:1-12.
doi: 10.1016/j.ahj.2019.02.011. Epub 2019 Mar 4.

Rationale and design of the Mechanistic Substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE): Effects of pitavastatin on coronary artery disease and inflammatory biomarkers

Udo Hoffmann  1 , Michael T Lu  2 , Devvora Olalere  2 , Elizabeth C Adami  2 , Michael T Osborne  2 , Alex Ivanov  2 , John Sukumar Aluru  2 , Saeyun Lee  2 , Nadja Arifovic  2 , Edgar Turner Overton  3 , Carl J Fichtenbaum  4 , Judith A Aberg  5 , Beverly Alston-Smith  6 , Karin L Klingman  6 , Myron Waclawiw  7 , Tricia H Burdo  8 , Kenneth C Williams  9 , Markella V Zanni  10 , Patrice Desvigne-Nickens  7 , Katharine Cooper-Arnold  7 , Kathleen V Fitch  10 , Heather Ribaudo  11 , Pamela S Douglas  12 , Steven K Grinspoon  10 ; REPRIEVE Investigators
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Rationale and design of the Mechanistic Substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE): Effects of pitavastatin on coronary artery disease and inflammatory biomarkers

Udo Hoffmann et al. Am Heart J. 2019 Jun.

Abstract

Background: People with HIV (PWH) have increased cardiovascular events, inflammation, and high-risk coronary atherosclerosis. Statin therapy has been shown to lower the risk of cardiovascular disease (CVD) in the general population, but whether this results from reductions in coronary atherosclerosis and is mediated by decreased inflammation remains unknown.

Methods: REPRIEVE is a randomized, placebo-controlled trial of pitavastatin calcium (4 mg/day) vs. placebo enrolling at least 7500 PWH between 40-75 years, on antiretroviral therapy (ART), with low to moderate traditional CVD risk. The Mechanistic Substudy of REPRIEVE (A5333s) is co-enrolling 800 participants from 31 US sites. These participants undergo serial contrast enhanced coronary computed tomography angiography (CCTA) and measurements of biomarkers of inflammation and immune activation at baseline and after 2 years of follow-up. The primary objectives are to determine the effects of pitavastatin on noncalcified coronary atherosclerotic plaque (NCP) volume, low attenuation plaque, and positive remodeling and on changes in immune activation and inflammation and to assess relationships between the two. Changes in CAD will be assessed in a standardized fashion by a core lab with expert readers blinded to time points and participant information; immune activation and inflammation assessment is also performed centrally.

Results: To date the Mechanistic Substudy has completed planned enrollment, with 805 participants.

Conclusion: This study represents the first large, randomized, CCTA-based assessment of the effects of a primary prevention strategy for CVD on high-risk CAD, immune activation and inflammation among PWH. The study will assess pitavastatin's effects on coronary plaque, and the interrelationship of these changes with biomarkers of immune activation and inflammation in PWH to determine mechanisms of CVD prevention and improved outcomes in this population.

Trial registration: ClinicalTrials.gov NCT02344290.

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Figures

Figure 1
Figure 1
Curved planar reformats of (A) baseline and (B) 1-year follow-up coronary CTAs in a 58-year-old woman living with HIV. A noncalcified proximal left anterior descending coronary artery plaque (arrows) increased in size while on placebo
Figure 2
Figure 2
Coronary computed tomography angiography (CCTA) (A) 3d volume rendering and (B) curved planar reformat through a proximal left anterior descending plaque. Plaque volume is quantified on the (C) short axis slice through the artery, with the (D) attenuation of plaque voxels categorized as noncalcified or calcified.
Figure 3
Figure 3
Timeline of REPRIEVE design changes and amendments
Figure 4
Figure 4
Mechanistic Substudy accrual figure. Dotted line shows actual accrual progress. Colored bands denote predefined NIH target enrollment zones: yellow (100%−75%), orange (75%−25%), red (<25%).
See this image and copyright information in PMC

References

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