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Cholesterol Lowering via Bempedoic Acid

Posted by susan.d 
Cholesterol Lowering via Bempedoic Acid
April 01, 2023 08:17AM

“Dr. Scirica: CLEAR Outcomes study evaluated bempedoic acid, which is an ATP citrate inhibitor. It lowers LDL by inhibiting the step above where statins work in the liver with the HMG-CoA reductase inhibitor, and it's been shown to lower LDL and is approved for lowering LDL and seems to have lower incidence of muscle-related side effects.

Bempedoic acid for cardiovascular outcomes

This study, CLEAR Outcomes was the study to evaluate its clinical benefit for cardiovascular outcomes in almost 14,000 patients. Now, the study was done predominantly in patients who were unable or unwilling to take statins, owing to either side effects or some other reason, and they were randomized either to bempedoic acid or placebo.

The primary outcome was the four-component MACE outcome of cardiovascular death, MI, ischemic stroke, and coronary revasc. And the average follow-up was about 40 months. Now, because these patients were not on statins, the mean LDL cholesterol at baseline was actually pretty high, about 139, so much higher than what we'll see in some of the other lipid trials, especially the PCSK9 inhibitors, where patients are on high-dose statins.

Significant reduction in LDL-C

But it was a population that wasn't taking statins, and bempedoic acid is a drug that seems to be tolerated in statin-intolerant patients, so it's a reasonable place to look. Now, over the course of trial, bempedoic acid did significantly reduce LDL cholesterol by about 30 mg/dL overall, which is about 21% compared to placebo. It did significantly reduce the primary end point with a hazard ratio of 0.87 with a highly significant P value.

Reductions in MI, stroke, and coronary revascularization

And that was driven predominantly by reductions in myocardial infarction, by stroke, and by coronary revasc, and not in cardiovascular death. Interestingly, in looking at the subgroups, there seemed to be even a greater reduction in the patients who were deemed primary prevention who probably had the highest LDL coming in compared to the secondary reduction, but other groups like age and sex were very similar in terms of their outcomes.

Results support the LDL hypothesis

So, I think this is a really important study for LDL hypothesis, which is alive and well. The percentage and the absolute reduction in LDL cholesterol on this trial corresponded to a clinical reduction in events that was very much in line, which was seen with other studies including the Cholesterol Clinical Trialists' Collaboration. So, the results in terms of clinical events were exactly what was to be expected from the results in terms of the LDL reduction.

LDL-C reduction with bempedoic acid and ezetimibe combined

I think, because there are many statin-intolerant patients out there, bempedoic acid is a really good option for those patients, especially when it's combined with ezetimibe, which works through a very different mechanism and will add additional LDL lowering. So, the combination of bempedoic acid and ezetimibe gives you about a 40% or so LDL reduction, which is very similar to a high-intensity statin.

So, I think it is good news for bempedoic acid. I think it's good news for the field, and I think it's good news for patients that there is now yet another agent that lowers LDL, that also reduces clinical outcomes.”
Re: Cholesterol Lowering via Bempedoic Acid
April 01, 2023 08:44PM
Interesting link Susan! Hope they are onto something
In my case the GP prescribed statins for me. I took them for 3/4 days then stopped.
Next blood test showed a reduction in blood lipid markers. He said good, the statins are working. Well, i just changed my eating habits...

So this Professor is totally wrong?

Re: Cholesterol Lowering via Bempedoic Acid
April 02, 2023 02:06PM
BA doesn’t reduce it as much as a statin. I have no symptoms while on Crestor so i’m staying on it. I only eat egg whites, dairy free, fish and chicken breast with no skin. However I’ve always been on this diet (my grown children as kids remarked in amazement that they ate at a friend’s house a yellow egg!) but without Crestor it’s super high and 5mg it’s very low.
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