Coronary Atherosclerotic Plaque Regression

Dawson LP, Lum M, Nerleker N, Nicholls SJ, Layland J.
Coronary Atherosclerotic Plaque Regression: JACC State-of-the-Art Review. J Am Coll Cardiol 2022;79:66-82.

The following are key points to remember from this review on coronary atherosclerotic plaque regression:

  1. This JACC state-of-the art review focuses on the novel treatment strategies that may induce atherosclerotic plaque regression, and the imaging modalities that can assess changes in plaque volume and composition. The speculation is that “as coronary imaging improves, it may become feasible and highly beneficial to use direct assessment of atherosclerotic plaque to more accurately inform decisions regarding initiation and titration of treatments” with emphasis on primary prevention. Should outcome data demonstrate reliable linking of imaging with plaque regression to reduction in cardiovascular (CV) events, monitoring plaque response may supersede surrogate markers such as coronary risk scores and lipoprotein levels.
  2. Until recently, it was believed that acute coronary syndromes (ACS) were caused by the rupture of small volume plaque that produce mild stenoses. More often, plaque enlarges rapidly within a few months of the acute event and progression is a necessary step prior to plaque rupture; changes that may not be detected by conventional coronary angiography until the plaque area to internal elastic lamina area increases above 40%. In contrast is the usefulness of imaging modalities that directly assess plaque burden.
  3. In persons with an ACS, 10-20% of nonculprit lesions progress within 8-12 months of initial presentation. High risk for progression includes those with a large plaque burden, a thin-cap fibroatheroma, low-attenuation, and positive vessel remodeling. Among patients with plaque progression, rates of subsequent events are about 15-20% at 12 months compared with <1% among patients without progression. Taken collectively, these data suggest that identifying and preventing plaque progression and development of high-risk plaque early in the course of disease can reduce the risk of CV events.
  4. Plaque regression historically measured by an increased luminal diameter may occur as a result of reductions in lipid and macrophage content, and inflammatory state. With advanced plaque imaging, both volume and composition can be assessed. Necrotic core volume, fibrous cap thickness, and positive remodeling predict risk of CV events; reductions might reflect a clinically relevant reduction in risk of CV events and could be considered plaque regression. Extensive total nonobstructive plaque burden has similarly increased risk of CV events as patients with obstructive but less extensive disease. The goal of plaque regression as a prevention strategy encompasses both the reduction of total plaque volume and the modification of plaque components to decrease the risk of plaque rupture. Importantly, not all plaque is modifiable (e.g., calcified plaque is rarely modifiable), so it is important to address changes early in a patient’s life.
  5. Table 1 in the article provides a comparison of the main imaging modalities. Assessment of the complete “coronary tree,” including plaque presence, morphology, and extent is an advantage of coronary computed tomography angiography (CCTA).
  6. Present treatments targeting plaque regression include dietary and lifestyle and pharmacological. While diet, exercise, and smoking are each associated with increased risk and are benefited by improved lifestyle, the impact on coronary plaque volume and composition is limited.
  7. There have been extensive evaluations of therapeutic approaches for plaque regression that have various pathways. Statins induce plaque regression in a dose-dependent manner and proportionally to reductions in low-density lipoprotein (LDL) cholesterol. With statins, fibrous and calcified plaque volume appear to increase, while noncalcified fibrofatty and necrotic core volumes decrease. Several studies demonstrated greater plaque regression with ezetimibe compared to optimal medical therapy, but the differences were not significant. The impact of each of the PCSK9 antibody classes of drugs was evaluated with intravascular ultrasound (IVUS) in relatively large studies: one stable coronary heart disease (CHD) and the other following an ACS. The impact was modest possibly because of the impact of high-intensity statins on plaque in all patients in both studies. Pure eicosapentaenoic acid was shown to reduce CV events in high-risk patients on statins, and in one study, greater plaque regression (-9.0% vs. +11.0%, p < 0.05) and change in composition.
  8. Importantly, colchicine, an anti-inflammatory that acts by inhibiting microtubule formation and the polymerization of tubulin results in suppression of inflammatory response was recently shown to reduce CV events following an ACS and in high-risk persons with stable CHD. In an open-label study of 80 patients with recent ACS on optimal medical therapy, after 12 months, colchicine therapy led to a significant reduction in low attenuation plaque volume (15.9 mm3 vs. 6.6 mm3; p < 0.05) and noncalcified plaque volumes, but the reduction in total atheroma volume was similar in both groups. The utility of assessing coronary plaque volume has been used to study several other drug classes with potential effect on coronary plaque including antihypertensives, anticoagulants, oral hypoglycemics (not yet for the SGLT2 inhibitors), testosterone, niacin, LDL apheresis, and high-density lipoprotein mimetics.
  9. In a recent meta-regression analysis of 17 prospective studies, each 1% reduction in percent atheroma volume was associated with a 20% reduction in odds of major adverse CV events. However, although this association may be present, there remains no direct evidence that plaque regression is linked with reduced CV events.
  10. Measuring coronary plaque volume and composition by CCTA is not easy nor readily available. It is likely that the process will be simplified and potentially more reproducible with use of artificial intelligence and possibly be applicable using a person as their own control.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Cardiovascular Care Team, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Anticoagulation Management and ACS, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and ACS, Interventions and Imaging, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging, Smoking

Keywords: Acute Coronary Syndrome, Anticoagulants, Antihypertensive Agents, Anti-Inflammatory Agents, Cholesterol, LDL, Colchicine, Computed Tomography Angiography, Coronary Disease, Diagnostic Imaging, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Life Style, Lipids, Myocardial Ischemia, Plaque, Atherosclerotic, Primary Prevention, Risk Factors, Smoking, Ultrasonography, Interventional

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