Applying Real-World Evidence in the Management of CAD/PAD - Episode 9

Case 2: Relationship Between LDL and Major Adverse CV Events

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Deepak Bhatt, MD, MPH: Kelley, let me turn to you about this patient. We’ve been focused on the antithrombotics on the stent or devices used and so forth. There is another aspect that I mentioned. It may be important or it may not be with this 66-year-old man with worsening claudication who is already in a walking program and who was just stented. His LDL [low-density lipoprotein] is 68 mg/dL. Is that too high, too low, or just right?

Kelley Branch, MD, MS: It’s always a good question because there are historical data with that U-shaped relationship with LDL in that patients with very low LDL seem to do worse. But that was in an era when we were looking at why people would have low LDL levels. Frailty and other diseases, such as liver disease, can be the reason they’re not synthesizing, which is why you would have these problems. Over time, we have been able to show a linear or, at the very least, a log-linear relationship with LDL decrease and improvement in outpatients too, specifically major adverse cardiovascular events. It didn’t matter all that much how you got there. The POSH trial showed that, if you move part of our intestines, that worked pretty well. It’s a slightly invasive way of doing it, but it worked very well.

With the data we have with the PCSK9s, from 2 large studies showing that we’re getting the LDL levels down to 30 mg/dL and even lower, those patients did better than the patients who were at goal by guidelines less than 70 mg/dL. We’re now able to achieve 30 mg/dL. If that’s better, how low do we go? Peter Libby said something that resonated with me at some point. He said that, based on these data showing that we’re getting the LDLs down to 20 or 10 mg/dL, we aren’t seeing the effects of demyelination and other concerns or increased mortality suggesting that LDL should be considered a toxin. If you consider it a toxin, then lower is better.

How do you get there? We have multiple ways to get there, and we should be striving to get it as low as possible because it seems like any LDL may be too much LDL, especially in patients like this who, even with an LDL of 68 mg/dL, are still having worsening symptoms. Atherosclerosis is still active, and this goes to the chronicity of atherosclerosis: This is ongoing, and it can be a progressive disease.

Deepak Bhatt, MD, MPH: Terrific. That’s been a great discussion of case No. 2.

Transcript Edited for Clarity