Key lessons on LDL-c and CV risk

The following key messages have been formulated based on an expert meeting among European cardiologists and internists, as well as other PACE-CME educational activities.

Click on the statements to read brief explanations of what the statements are based on, including slides and references.

LDL-c biology/atherogenesis

• Elevated LDL-c is causal of atherosclerosis
• LDL-c level increases with age, so does the risk of atherogenesis
• The atherosclerosis disease process changes with time and LDL-c level, and treatment effect depends on the disease phase
• Regression of atherosclerotic plaque is possible with adequate lipid-lowering therapy
• Side effects are not the effect of LDL-c lowering and achieved LDL-c level
• When lowering plasma cholesterol, this does not affect cholesterol present in membranes
• Lowering LDL-c profoundly to very low levels is safe

Therapeutic considerations

• Use combination therapy for additive LDL-c lowering effect to reduce CV risk
• Even below LDL-c target, further LDL-c reduction gives additional CV benefit
• Greatest risk reduction can be achieved in the highest risk groups
• Statin therapy is remarkably safe
• When statin therapy is discontinued, the risk of CV events and mortality increases
• After an event, initiate the right treatment in hospital
• LDL-c lowering treatment impacts disease progression before clinical manifestation
• Screening for familial hypercholesterolemia after ACS pays off

Concept changes in lipid-lowering therapy to lower CV risk

Based on the key lessons listed above, the following principles can be formulated that should form the basis of lipid-lowering therapy to lower CV risk.

1. Use combination therapy

2. Start early

3. Treat more aggressively

Emerging concept of multifactorial CV risk management

In addition to lipid-lowering, a broader concept of CV risk management in coronary disease is emerging, which should include:

1. Lipoprotein-modifying therapy: lower LDL-c earlier and more aggressively (and triglyceride-rich lipoproteins and Lp(a)).

2. Blood pressure-lowering therapy: target SBP 120-130 mmHg (note U-curve).

3. Novel diabetes agents with CV benefit (CAD and/or risk of HF events with GLP-1ra and/or SGLT2i

4. Antithrombotic therapy: prolonged double antiplatelet therapy? Low-dose anticoagulation?

5. Anti-inflammatory therapy: target IL-1β

6. Future: target microbiome …?

Better algorithms on which patient to treat when with what, and better risk estimation are needed. Moreover, there is a need for better risk prediction of adverse events. 

Download the slides