Reflections on the Current and Future State of LDL Lowering

Recently, our Chief Scientific Officer Dr. John Kastelein spoke with Dr. Alain Bouchard on his podcast, MyHeart.net. Dr. Bouchard is a clinical cardiologist at Cardiology Specialists of Birmingham, Alabama, US. In an episode titled "Non-Statin Therapies for LDL Cholesterol Lowering", these experts discuss the role of statins in the treatment of patients with atherosclerotic cardiovascular disease (ASCVD), which has been well demonstrated to lower major cardiovascular events. They also explore the benefits of combination therapy for low-density lipoprotein (LDL) lowering in ASCVD.

Here are the top takeaways from the discussion:

1. We can still go lower with LDL and reap benefits  

We do not believe we have reached the point of LDL reduction where there is no more benefit. The relationship between LDL and benefit is a straight line, which is very unusual for biology because almost all relations are curved and not completely linear. At some point, the benefit plateaus, and the line goes flat. With LDL, we haven’t reached that point yet.

2. Introducing combination therapies early on could be beneficial for patients

The standard of prescribing the highest dose of the most intensive statin therapy is not working for a large portion of the population. This is done in the ASCVD field, but not in the hypertension or diabetes fields. In these other areas of medicine, introducing combination therapies early on is much more standard of practice.

3. Access is a major hurdle for innovative, high-potency LDL-lowering therapeutics

There are only a few non-statin therapeutic options for patients. The pill forms of non-statin medicines tend to have low efficacy unless used in combination with a statin. If a patient needs to have a bigger LDL-lowering effect, injectables have been the best way to go. However, injectables are very difficult to get reimbursed. In Europe, only 8 of 100 lipid-lowering prescriptions are filled with an injectable, simply because of insurance companies’ or government reimbursement policies. This low rate demonstrates not only the need for high-potency, LDL-lowering therapeutic options, but for financially accessible therapeutic options for patients at risk of cardiovascular disease.  

4. CETP inhibition has promising results that provide hope for future treatment options

Genetically low cholesteryl ester transfer protein (CETP) activity in humans is associated with fewer heart attacks, fewer strokes, less chronic kidney disease, and less heart failure. The inhibition of CETP has been observed to reduce LDL cholesterol levels and increase high-density lipoprotein (HDL) cholesterol levels. REVEAL was the first randomized controlled trial to demonstrate that combining CETP inhibitor therapy with intensive statin therapy significantly reduces the risk of major coronary events. The goal of current and future research into this area is to leverage these genetic insights for the development of treatment options for people living with ASCVD and familial hypercholesterolemia.

We encourage you to also listen to the second discussion Dr. Kastelein shared with Dr. Bouchard, where they discussed the HDL Conundrum and the role of HDL cholesterol in the development of atherosclerosis and cardiovascular morbidity and mortality. To hear more from Dr. Kastelein, listen to his appearance on Dr. Peter Attia’s podcast, The Drive.