Dr. Steven Nissen, cardiologist and Chief Academic Officer of Cleveland Clinic’s Heart, Vascular, & Thoracic Institute, talks about an alternative for statin-intolerant patients.
Interview conducted by Ivanhoe Broadcast News in 2023.
What is cardiovascular disease and how common is it?
Nissen: Well, heart disease is the number one cause of death amongst both men and women in the United States and in most developed countries. And it is increasing in frequency in developing countries and we’ll probably soon, in those countries, become the leading cause of death.
Tell me about CLEAR Outcomes trial, what was the purpose of the trial?
Nissen: Statins, which lower cholesterol are the gold standard for treatment of high cholesterol. They lower the bad cholesterol, that’s LDL cholesterol substantially, and they’re used by tens of millions of people in United States and around the world even more. The problem is that there are some people, probably about 10-15% of the population that just don’t tolerate statins. They typically complain of muscle-related symptoms and often they’ve tried multiple statin drugs and they simply don’t tolerate them. These people still need cholesterol lowering. So the CLEAR Outcomes trial was designed to test a drug that works by a different mechanism from statins and is not likely to cause muscle-related side-effects.
How is it that bempedoic acid is different than statins?
Nissen: Bempedoic acid is taken orally. When it gets into the bloodstream, it’s inactive. It’s taken up by the liver, which is where statins work, and it works along the same pathway as statins. But in the liver, it’s activated into a form that actually is inhibiting an enzyme involved in cholesterol synthesis. Since the drug is inactive in the circulation until it gets to the liver, it’s not capable of causing muscle related adverse effects, like we see with statins.
Is it as effective as statins?
Nissen: The cholesterol lowering from bempedoic acid is moderate. It’s in the range of 20-25%. Full doses of the most effective statins can lower cholesterol by 40% or more. So bempedoic acid does lower cholesterol. It’s a bit less effective compared with statins, but it can be combined with another drug known as ezetimibe and the two together can lower the bad cholesterol, that’s LDL cholesterol in the range of 35-40%, which gives us a pretty good alternative to statins.
What are the risks?
Nissen: Bempedoic acid does have some adverse effects. The most prominent one is that it can increase the risk of gout. About a 1% absolute increase in the risk of gout. It also can increase the risk of gallstones. Those two adverse effects are the most common.
What were the results of the trial?
Nissen: So in, about 14,000 patients, half of them were given a placebo pill, and half of them were given bempedoic acid. All of them were unable to take statins. So 100% of this population was statin intolerant. In the group that got bempedoic acid, there was a reduction in the risk of the endpoint of cardiovascular death, heart attack, or stroke, was about 13% reduction. But importantly, there were larger reductions in the risk of heart attack alone, it was 23%, and there was a very substantial reduction in the need for procedures on the coronary artery, such as stenting or bypass surgery, that was reduced to about 19%. So overall, we saw substantial reductions in the complications of coronary disease in these patients. And these patients, by the way, included both patients that had a prior heart related event like a heart attack, and people that were at high risk for our first event and both groups showed benefit.
Are the result different for men and women?
Nissen: Results were very similar, almost identical in men and women. Women were 48% of the enrolled patients. It was one of the highest fractions of women in any trial that has been done in recent memory and that was deliberate, we really wanted to get a good answer for both genders and both genders benefited.
Who would benefit the most from this medication?
Nissen: This medication is really well-suited to people who have tried multiple statins, cannot tolerate them, and have a need to lower their bad cholesterol, LDL. That’s a large number of people, particularly if you look globally. But those people who can’t tolerate statins are good candidates to be treated with bempedoic acid.
Is there anything else you want to add?
Nissen: This drug, bempedoic acid actually did two things: it lowered the bad cholesterol, LDL, but it also lowered the levels of inflammation, which we measure as high sensitivity CRP. In both cases we got about a 22% reduction, 22% reduction in the bad cholesterol, and about a 22% reduction in high sensitivity CRP, a measure of inflammation. We think that both of those factors played a role in the favorable outcomes that we observed with bempedoic acid
END OF INTERVIEW
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