Coronary atheroma regression and adverse cardiac events: A systematic review and meta-regression analysis

Abstract

Meta-regression analysis of trials using intravascular ultrasound to assess regression induced by lipid medications was performed. • A 1% decrease in percent atheroma volume was associated with approximately a 20% reduction in the odds of incurring a major cardiovascular event.• Percent atheroma volume changes represent a surrogate measure of cardiovascular events. A R T I C L E I N F O Keywords:Atherosclerosis Plaque regression Major adverse cardiac events Intravascular ultrasound Anti-atherosclerotic therapy A B S T R A C TBackground and aims: The relationship between plaque regression induced by dyslipidemia therapies and occurrence of major adverse cardiovascular events (MACE) is controversial. We performed a systematic review and meta-regression of dyslipidemia therapy studies reporting MACE and intravascular ultrasound (IVUS) measures of change in coronary atheroma. Methods: Prospective studies of dyslipidemia therapies reporting percent atheroma volume (PAV) measured by IVUS and reporting death, myocardial infarction, stroke, unstable angina or transient ischemic attack (MACE) were included. The association between mean change in PAV and MACE was examined using meta-regression via mixed-effects binomial logistic regression models, unadjusted and adjusted for mean age, baseline PAV, baseline low density lipoprotein-cholesterol and study duration. Results: The study included 17 prospective studies published between 2001 and 2018 totaling 6333 patients. Study duration varied from 11 to 104 weeks. Mean change in PAV, across the study arms, ranged from −5.6% to 3.1%. MACE ranged from 0 to 72 events per study arm: 13 study arms (38%) reported no events, 8 (24%) reported 1-2 events and 13 (38%) reported 3 or more events. Meta-regression demonstrated a decline in the odds of MACE associated with reduction in mean PAV: unadjusted odds ratio (OR): 0.78, 95% Confidence Interval (CI): [0.63, 0.96], p = 0.018; adjusted OR: 0.82, 95% CI: [0.70, 0.95], p = 0.011, per 1% decrease in mean PAV. Conclusions: A 1% reduction in mean PAV as induced by dyslipidemia therapies was associated with a 20% reduction in the odds of MACE.

Nanoparticle-based “Two-pronged” approach to regress atherosclerosis by simultaneous modulation of cholesterol influx and efflux

“…Reduction in total or aortic arch plaque area by ~20% and ~60% decrease in aortic arch FC or CE is comparable to the reduction in plaque area evaluated by Feig et al using the transplantation model [48]. It is noteworthy that meta analyses of 17 prospective studies published between 2001 and 2018 (Total 6333 patients) where changes in percent atheroma volume were measured by IVUS indicated that a 1% reduction in mean plaque volume was associated with a 20% reduction in the odds of major adverse cardiovascular events or MACE [49]. The observed reduction in atherosclerotic plaques of >20% following treatment with "Two-pronged complex" underscores the significance of this therapeutic strategy for reducing the burden of atherosclerotic disease.…”

Atherosclerotic Coronary Plaque Regression and Risk of Adverse Cardiovascular Events

“…The PAV was calculated as done previously . Mean change in PAV was obtained as follow-up minus baseline PAV.…”

“…2 The use of intravascular ultrasound (IVUS) has become a globally established method to evaluate the effect of lipid-lowering therapies (LLTs) on atherosclerotic plaque through accurate serial measurements of atheroma burden. Studies by Bhindi et al 3 and others 4 have shown that changes in percent atheroma volume (PAV) defined by IVUS represent a potential surrogate measure of cardiovascular events. With the advent of new clinical trials demonstrating the benefit of early initiation of intensive LLT on plaque burden in high-risk patients, 5,6 we evaluated the association between plaque regression and MACEs by providing an updated systematic review and meta-regression analysis of lipid treatment trials reporting MACEs and IVUS measures of change in coronary atheroma.…”

Intensive lipid lowering agents and coronary atherosclerosis: Insights from intravascular imaging

“…Clinical studies have demonstrated that the burden and progression of coronary atherosclerosis on IVUS associate with prospective cardiovascular risk [8] . These studies demonstrate that patients experiencing a clinical event have a greater increase in percent atheroma volume (PAV) of 0.55% compared with those that remain event free [8] and that therapeutic induced regression of PAV by 1% associates with a 20% reduction in the rate of major adverse cardiovascular events [9] . However, IVUS imaging is limited in its ability to characterize the composition of coronary atherosclerosis, beyond detection of calcium and evidence of echogenicity and attenuation, which have been reported to associate with more vulnerable plaques [10] .…”