Why do we fail to achieve Glagovian atheroregression in lipid-lowering trials?

Abstract

• Reduction of total atheroma volume provides cardiology with a hope to reverse atherosclerosis in hands of the modern-day lipidlowering medications: • ASTEROID and SATURN trials demonstrated the potential of statins which reduce the total atheroma volume up to 6.38 mm3 in coronary arteries and 30% decrease in outcomes; • Recombinant ApoA-I Milano demonstrated a 14.1 mm3 reduction in total atheroma volume with unproven effect on clinical outcomes; • ZEUS trial with ezetimibe revealed an 8.2 mm3 atheroregression. • The plaque burden with a Glagovian threshold of 40% (PAV [percent atheroma volume] above 40% at the baseline, and below 40% at the follow-up) is the ultimate criterion of the clinically valuable lesion we are able to examine in order to judge the genuine Glagovian atheroregression. • Some methodological flaws of the modern-day interventional imaging approaches including improper interpretation of the vessel contours, misunderstanding of such parameters as total atheroma volume and PAV, absence of the unified CoreLab expert methodology for assessment of both intravascular and noninvasive coronary imaging significantly impact results and further progress in this field: • There is a difference in methodology how to assess plaque burden between histology of Glagov and IVUS-imaging of Nissen; • Neither intravascular intravascular ultrasound (IVUS) or optical coherence tomography nor noninvasive computed tomography angiography allow us to comprehensively distinguish all the artery layers; • External elastic membrane and adventitia could be quantitatively assessed by IVUS only; • Some new medications as well as progress in the development of the bioresorbable scaffolds and nanomedicine promise to revolutionize the cardiovascular biomedicine with the main goal to achieve Glagovian atheroregression below 40% threshold of the PB: • The bioresorbable scaffold Absorb BVS (Abbott Vascular, CA, USA) is the first coronary device which has shown phenomena such as late lumen enlargement and wall thinning with at least 12% reduction of plaque burden; • NANOM-FIM trial of plasmonic photothermal therapy with silica-gold nanoparticles showed truly unprecedented 60.3 mm3 plaque volume reduction. • The modern-day statin trials were conducted in patients with relatively small lesions when PAV never exceeded 40% and without proper methodology, which means that the revealed phenomenon of atheroregression is essentially the pseudo reduction of the atheroma volume. • The PAV or plaque burden is the only parameter to describe changes in the vessel geometry from the Glagov phenomenon point of view because it mathematically reflects patterns between both vessel and lumen size. • IVUS with assessment of plaque burden remains the golden standard to evaluate atheroregressive patterns of medications or medical devices in clinical trials: • Trials with the baseline PAV above 40% demonstrated higher potential of the plaque burden reduction; • Further comprehensive analysis is required in order to validate the genuine threshold of the artery enlargement between a 20 and 55% PAV when positive correlation between lumen area and PB gets replaced by the negative correlation with the progressive narrowing of the lumen.