With so many drugs now available to lower cholesterol, people naturally would like to know about the benefits and risks of each. We have written quite a bit about the side effects of statins such as atorvastatin (Lipitor), rosuvastatin (Crestor) and simvastatin (Zocor). Probably the most troublesome side effect patients report on one of these drugs is muscle pain or weakness. But what about ezetimibe (Zetia)? As it turns out, Zetia may cause muscle problems, too.
Muscle Pain on Zetia:
Q. I have tried many statin drugs for cholesterol, but all gave me muscle pain and cramps. My doctor put me on Zetia and insists it can’t cause muscle pain since it is not absorbed into the blood stream. I still have muscle pain, cramps and tingling in my legs and feet. Can Zetia cause this?
A. Although Zetia works differently from statin cholesterol-lowering drugs such as Lipitor or Zocor, it is absorbed into the bloodstream. Muscle side effects seem to be less common with Zetia than with the statin drugs, but Zetia may cause muscle problems. It would be appropriate to discuss your treatment with your doctor to see if there is another approach that might suit you better.
Study on Ezetimibe Yielded Disappointing Results:
Another reader wrote us shortly after learning of the results of a study that raised questions about ezetimibe:
Q. There was a lot of hoopla recently about the drug Zetia. I called my doctor, who told me to continue taking it, but if it’s not doing anything good for my high cholesterol, why bother?
A pharmacist told me that the FDA hasn’t recalled it, so it must be all right. Can you shed any light on this?
A. Zetia (ezetimibe) and Vytorin (ezetimibe and simvastatin) lower cholesterol. The unresolved question is whether they prevent atherosclerosis, heart attacks and strokes.
ENHANCE Raised Questions:
The study you heard about was called ENHANCE because the company hoped Vytorin would be better than Zocor (simvastatin) alone. Scientists compared the thickness of the lining of the carotid arteries in the neck between people put on Vytorin and those on simvastatin (Kastelein et al, New England Journal of Medicine, Apr. 3, 2008). Vytorin lowered bad LDL cholesterol more than Zocor did but this did not lead to healthier arteries.
Cardiologists Reacted to the News:
Cardiologist Steven Nissen, MD, of the Cleveland Clinic said he was shocked by the results. He advised his colleagues not to prescribe Zetia except as a last resort. He was not the only one to see ezetimibe in a less positive light. Here is another question we got from a reader around that time:
Q. I am alarmed by recent reports that Vytorin and Zetia are associated with plaque build-up in the carotid artery. My doctor tells me that until more is known, I should continue taking the prescribed medicine. Do you agree? Is it harmful to switch abruptly to another cholesterol-lowering medicine such as simvastatin?
A. In the wake of the ENHANCE study that produced such disappointing results with Vytorin, the American College of Cardiology convened an expert panel to advise their colleagues. These thought leaders suggest that doctors should stick with statin-type cholesterol-lowering drugs, which have a proven track record.
Until there is more convincing data about Vytorin or Zetia, the cardiologists recommend using them only as a last resort. There should be no danger switching to simvastatin, since it has been shown to be effective at lowering cholesterol and reducing the risk of heart attacks in people with heart disease (Ursoniu et al, Pharmacological Research, online June 9, 2017).
Is There Still Any Reason to Use Zetia?
Nearly a decade after the ENHANCE data were reported, cardiologists have taken another look at the value of ezetimibe (Bays et al, Journal of Clinical Lipidology, online May 8, 2017). The investigators note that many people stopped taking Vytorin or Zetia after they learned about this trial. That’s too bad, they say. They found that when people dropped ezetimibe their cholesterol rose. That increased their predicted risk of cardiovascular disease. They do not have data to show whether people who stopped taking Zetia had more heart attacks or strokes, so the jury is still out on that.
Moving on to More Expensive Drugs:
Within the past few years, FDA has approved new drugs to lower cholesterol. Evolocumab (Repatha) and alirocumab (Praluent) are PCSK9 inhibitors. They lower cholesterol dramatically through a different mechanism from statins. Repatha has been shown to reduce the risk of heart attack and stroke (Sabatine et al, New England Journal of Medicine, May 4, 2017). Unfortunately, it didn’t reduce the risk of dying from cardiovascular causes.
At this time, these pricey medications are considered appropriate for treating people with familial high cholesterol. Sometimes, however, doctors find it hard to resist reaching into their toolbox for the newest thing that might help. Consequently, we expect that other patients might end up taking them. We don’t know how the benefits and risks of PCSK9 inhibitors will play out over time.
You can learn more about these medications from our interview with Dr. Steve Nissen about the GAUSS-3 trial of evolocumab and ezetimibe in people who have muscle pain on statins. It is Show 1031. In the meantime, keep in mind that Zetia may cause muscle pain itself.