April 29, 2024

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Intensifying Statin Therapy to Reduce “Bad Cholesterol” and Potentially Dissolve Plaques?

Intensifying Statin Therapy to Reduce “Bad Cholesterol” and Potentially Dissolve Plaques?



Intensifying Statin Therapy to Reduce “Bad Cholesterol” and Potentially Dissolve Plaques?

Atherosclerotic plaques, the result of complex interactions involving lipid deposition, inflammatory changes, cell migration, and arterial wall damage, are the pathological and physiological driving factors of atherosclerotic cardiovascular disease (ASCVD).

Therefore, preventing plaque formation, stabilizing existing plaques, and promoting plaque regression are potential methods to reduce the occurrence of ASCVD events.

Various invasive and non-invasive methods, such as intravascular ultrasound (IVUS), optical coherence tomography (OCT), near-infrared spectroscopy (NIRS), and coronary computed tomography angiography (CCTA), can be used to characterize atherosclerotic plaques.

A recent review published in Nature Reviews Cardiology provides an overview of diagnostic and therapeutic approaches for stabilizing and regressing atherosclerotic plaques.

Intensifying Statin Therapy to Reduce "Bad Cholesterol" and Potentially Dissolve Plaques?

screenshot from Nature Reviews Cardiology


Strategies for Stabilizing and Regressing Atherosclerotic Plaques:

  1. Pharmacological Treatment:

    • Statin Drugs: Clinical trials analyzing statin therapy based on IVUS suggest that statin treatment, by reducing plasma low-density lipoprotein cholesterol (LDL-C or “bad cholesterol”) levels, can stabilize or regress plaques in patients with chronic coronary artery disease (CAD) or acute coronary syndrome (ACS). Higher intensity statin therapy may be more effective than lower intensity treatment.
    • Ezetimibe: Used in conjunction with statins when statin monotherapy is inadequate, ezetimibe has limited evidence supporting plaque regression, and its cumulative effect on plaque morphology remains uncertain.
    • PCSK9 Inhibitors (Alirocumab, Evolocumab): These inhibitors, used for secondary prevention and primary prevention in high-risk cardiovascular patients, have shown beneficial effects on plaque regression and stability when added to statin therapy.
    • Bempedoic Acid: An ATP citrate lyase inhibitor that lowers plasma LDL-C levels in statin-intolerant patients; however, its impact on plaque stability or regression is yet to be evaluated.
  2. Lifestyle Changes:

    • While dietary changes, such as adopting evidence-based heart-healthy diets like the Mediterranean diet, remain foundational for preventing and managing ASCVD, their specific benefits on plaque regression have not been confirmed in large, well-controlled randomized clinical trials.

Comprehensive Assessment of Plaque Status:

Invasive and non-invasive imaging techniques can be utilized to evaluate overall plaque burden and local plaque characteristics.

  1. Invasive Methods:

    • IVUS: Traditional imaging technology in clinical trials for assessing coronary artery plaque burden.
    • OCT: Provides higher resolution and detailed images of superficial arterial wall microstructure.
    • NIRS: Allows imaging of lipid content in atherosclerotic plaques, providing an opportunity to assess changes in plaque composition.
  2. Non-invasive Methods:

    • CCTA: A rapidly evolving non-invasive method for assessing plaque burden and composition.
    • MRI: Potentially evaluates features such as coronary artery wall thickness, stenosis, and positive remodeling.
    • PET: Visualizes inflammatory and calcified regions of plaques but has limitations in resolution.

Exploring Therapies Targeting Lipoprotein(a) to Reduce Residual Cardiovascular Risk:

Despite significant reductions in serum LDL-C levels, some patients still face substantial residual cardiovascular risk.

Factors contributing to residual ASCVD risk include residual lipoproteins, lipoprotein(a), and cardiac metabolic factors.

Future trials may focus on interventions targeting other endpoints, such as lipoprotein(a) levels, to impact plaque regression and stability, thereby reducing residual risk.

Intensifying Statin Therapy to Reduce “Bad Cholesterol” and Potentially Dissolve Plaques?

(source:internet, reference only)


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