Why are doctors still prescribing Zetia?

A health research company just released a list of the 100 top drugs in America according to sales. 29th on the list, with sales of over $1.8 billion, is the cholesterol lowering drug ezetimibe, brand name Zetia.

This drug was released over 10 years ago because it worked really well in combination with statin drugs such as Zocor (simvastatin) to lower LDL cholesterol levels. It was released as a single agent and combined with simvastatin as Vytorin. The only problem was that in 2008 a study of the ezetimibe/simvastatin combination compared to simvastatin alone showed the combination did not improve measurements of arterial wall thickness which correlates with things like heart attacks and strokes.

Although cholesterol levels were lower in the combination arm, simvastatin was just as effective in achieving the more meaningful outcome. Ezetimibe appeared to increase cancer risk in another study, evaluating patients with aortic stenosis. A study which compared adding niacin or ezetimibe to statin therapy in patients with coronary heart disease in 2009 showed that, even though ezetimibe was very effective in reducing LDL cholesterol levels, it also increased the thickness of the arterial walls when compared to niacin. Niacin wasn’t nearly as good at reducing cholesterol levels as ezetimibe, but there were more cardiovascular deaths in the ezetimibe group.

This drug, whose only claim to fame is that it reduces a number on a chemistry panel, continues to be popular in both the US and Canada. An editorial in the Journal of the American Medical Association in 2014 wondered at the failure of very convincing evidence to make us stop prescribing it. The author concluded that it must be that the manufacturer (Merck) has been very effective at marketing ezetimibe and that patients’ and doctors’ fixation on reducing the cholesterol numbers has made it attractive in defiance of its lack of efficacy. Statin drugs, which also are not immune to controversy, may reduce the risk of heart attacks by reducing inflammation, not by reducing cholesterol levels per se. Since ezetimibe acts to reduce absorption of cholesterol from the gut, it may have no effect at all on inflammation or vascular health despite lowering cholesterol levels.

There are further studies still in the pipeline which may clarify the situation a bit more. It seems right now, though, that there is enough evidence that this is a bad drug for the Food and Drug Administration to rescind its approval. It would be nice to believe that physicians would take the initiative to change their prescribing habits, removing $1.8 billion dollars from our health care bill while reducing our patients’ pill burden, but apparently we are not stepping up to the plate.

Janice Boughton is a physician who blogs at Why is American health care so expensive?

Comments are moderated before they are published. Please read the comment policy.

  • Dr. Drake Ramoray

    There was a downtick of Zetia prescriptions by referring doctors in my area until quite recently. I have increasingly noticed additional use of the medication as providers join big hospital groups, ACO’s, and are looking to be subjected to pay for performance. LDL goal is a major measure. I don’t believe it is a coincidence.

    I can’t comment on Canada.

  • Eric Strong

    A classic example of physicians focusing on a number instead of the patient.

    • querywoman

      Absolutely! Doctors need to pay more attention to illnesses with real symptoms!

      • LeoHolmMD

        It is absurd how much the prevention and disease trolling agendas have displaced patients immediate concerns.

        • querywoman

          I am in my fifties and it’s been this way most of my adult life.
          I have written before, without getting much feedback, that it’s only been for about a hundred years that doctors have been able to really help anyone.
          It’s hard to believe that doctors of yore could only bleed a person. I do know they could prescribe painkillers and purge a person.
          Prehistoric folks drilled holes in skulls and there is evidence that people healed after them.
          Antibiotics and insulin are socially new.
          What about urinary infections? I have a long history of them, but I can go for years without one. Were they fatal without antibiotics?
          The last time I had one, I researched the internet, also a new thing to do, and found that parsley is a good diurectic. It worked, even old dry parsley flakes?

          • Suzi Q 38

            Does parsley really work?

          • querywoman

            For me it did! Had me peeing good, even when I used old dry parsley.
            It was better than cranberry juice.

          • Suzi Q 38

            How do you ingest it?
            Do you sprinkle the dry flakes on food?
            if so, how much?
            Do you take it everyday?

          • querywoman

            I certainly wouldn’t take parsley pills. It tastes good, so put it in your food.

            I probably cooked it up with something like potatoes and water. I rehydrated it.
            You could certainly try adding it to your food every day.
            I had to go a health food store to get fresh parsley.
            Brew up some parsley tea with the fresh stuff.
            Parsley is a diuretic. It may help with weight loss, no guarantee.
            But daily use of parsley should help you pee better. It won’t hurt to try.

          • querywoman

            Hey, Suzi Q, did you ever try the parsley as diuretic? It makes sense that, if you are trying to pee, you should use it as a tea or soup with plenty of water.

  • James O’Brien, M.D.

    In a related question, why are doctors still focusing on LDL instead of LDL-P? Numbers versus outcomes and all that…



    For the same reason that baseball managers used to focus on batting average and not on base percentage…

    • ninguem

      My guess is that, much like the Zetia thing, because the docs get weary of this year’s Latest Greatest Thing That All Doctors Must Do, And They’re Quacks If They Don’t…….will be found worthless and replaced by something else next year.

      Oh, never mind, now it’s LDL, no wait, it’s LDL-P.

      What lipoprotein will it be next year? What meta-analysis or other statistical trick will be played to amplify a tiny insignificant difference into something significant…..until it isn’t.

      The magazines say Butter is OK now.

      I tend to worry more about getting the patient’s weight down to Earth, stopping the cigarettes and exercising once in a while.

      • James O’Brien, M.D.

        I’d agree with you if it were new information but this has actually been out for some time now.

        I think this illustrates why one does not necessarily follow treatment guidelines of KOLs and one needs to make their own judgments.

        Hard to argue with your last point but for the 50 year who is in good shape and is eating right and exercising, LDL-P analysis might be lifesaving. I speak from experience.

  • LeoHolmMD

    Not sure why anyone is still paying for Zetia. Oatmeal has better evidence behind it.

  • PrimaryCareDoc

    How much of this has to do with achieving the “proper” quality reporting scores? For PQRS, the benchmark is achieving an LDL<100 in patients with CAD. Some patients are not going to get there with just a statin, so the doctor adds Zetia. Voila! Everyone is happy- the doctor is getting good "quality" scores, Medicare has achieved its pointless metrics, and Merck continues to rake in the big money. Oh, everyone except the patient, that is. He's been prescribed and expensive, worthless and potentially harmful drug.

    But true patient care doesn't matter anymore. We just need to satisfy the bean-counters.


    • DeceasedMD

      yes truly it is all turning into the walmart of medicine: walmart quality and walmart service. Can I help the next in line?

    • Acountrydoctorwrites

      I agree. Physicians are no longer encouraged or expected to read the literature themselves. Our EMRs and our quality reports are still built around the old guidelines. The perception is still out there that doctors who decide, based on their reading, to ignore the guidelines are causing harm to their patients. Sometimes it is the other way around: the obedient followers are the ones causing harm to unsuspecting patients.

      • Suzi Q 38

        My doctor was one of them, and I consider him to be a good doctor.

    • querywoman

      It’s not just the bean counters. SOME doctors have practicing that revolve around preventive medicine guidelines, and don’t know how to treat illnesses with symptoms!
      An endocrinologist just had to do cholesterol testing on me in the early 1990s, when it really came into vogue. Yet, I had been bleeding 15 days a month for two years, and the thought that I was not ovulating never entered his mind.

      • HJ

        You forgot diabetes…

        What could they do besides blood pressure, cancer, cholesterol, diabetes and all that other preventive testing?

        • querywoman

          I sort of consider diabetes testing worthwhile. Nevertheless, although I got regular blood tests annually due to a thyroid problem, and that includes glucose monitoring, I did not get diabetes med till I had a 325 fasting blood sugar.
          So what good were the screenings?

          • Suzi Q 38

            My fasting is about 80-90 in the morning, without my meds or anything to eat. I believe that when my numbers were higher(90-110), that it was a side effect of my statin and food selection the night before. When I stopped taking my statin, my blood sugars decreased and were more predictable and less erratic.

        • querywoman

          Diabetes also has symptoms!

        • Suzi Q 38

          Diabetes can also be brought on by the use of statins and other medications.

  • QQQ

    “A health research company just released a list of the 100 top drugs in
    America according to sales. 29th on the list, with sales of over $1.8

    $1.8B??? You big pharma is happy!

  • Ashish Advani

    Granted, that 2008 Vytorin study (ENHANCE) was a huge backfire. But, the good news for Merck/ SP was that CA IMT (arterial thickness) is a surrogate marker, meaning all it could tell us was an effect on an image, and nothing clinically relevant. If I recall correctly, ACC/AHA and NLA came out and said this was nothing more than an imaging study.

  • T H

    Until clinicians and insurance companies that pay for meds demand studies that show Absolute Risk Reduction, Number Needed to Treat, and have clinical outcomes instead of surrogate outcomes, nothing is going to change regarding meds.

    This holds true for the various numbers we are expected to be treating in vital signs, cholesterol, eye pressure, etc. Fortunately, some of them have been elucidated. Now, if only the medications that bring abnormal numbers into the accepted normal range actually changed the patient’s clinical course…

  • querywoman

    I took it briefly for a while, along with simvastatin, a few years ago. I wondered why I had to please somebody’s d@mn numbers! I thought I was on enough chemicals already!
    I was slowly inching into mild hypothyroidism, which raises cholesterol. And, experiencing really low heart beat a couple of time.
    My levothyroxine dose was raised a tiny bit for the first time in years and my cholesterol went down.

    • SarahJ89

      I was treated for “treatment refractory depression” for over 20 years, during which time I had sudden weight gain (after a lifetime of being 20-30 pounds underweight), depression, chronic fatigue, high cholesterol, dry skin and hair, low temperature, sensitive to cold (and heat, after menopause) and a host of other classic hypothyroid symptoms. The depression was caused by hypothyroidism, disappeared never to return after the first couple of weeks on levothyroxine. Those first weeks felt as if I was rising from the dead. I had to find a whole new way of living after being in the ditch for 20+ years.

      As long as my TSH is on or near 1.0 I’m , healthy and productive. But I lost a career and nearly killed myself because I felt so horrible all the time. I will never understand why anyone bothered to compile that list of hypothyroid symptoms if it gets overruled by TSH results. (Mine were “low normal.” They hadn’t changed since the onset of symptoms in my late twenties, but I finally got someone to write a prescription. With treatment I am fine and able to work. I love to work.)

      I spent 20 years having ineffective and dangerous psychotropics being shoved down my throat, narrowly escaped useless and demeaning ECT. The only thing that saved my butt was my propensity for “noncompliance.” I learned in that experience to have no confidence in doctors, a lesson I would prefer to have skipped.

      I am, however, totally compliant with my levothryoxine. Mainly because it works. The focus on numbers, to the exclusion of looking at symptoms has not served me well.

      • querywoman

        Sarah, I have a long history of serious menstrual problems related to thyroid dosage adjustments. Of course, my problem was anxiety, depression, and mood swings, even when I bled 15 days a month for 24 cycles. That caused anemia, which resulted in more depression, dizzy spells, and physical weakness.
        Birth control pills helped regulated my cycle. I did not get to have children.
        Around about age 40, I started really going into diabetes. Metformin, which is good for polycystic ovarian disease, was always good for me.
        Ate age 43, I went on insulin. My periods began to get lighter and lighter, no cramping, and within 6 months mostly disappeared.
        I have never had any symptoms of menopause.
        I was just telling my current endo about this.
        The diabetes/insulin resistance/PCOS problems should have been obvious to my past doctors.
        I think I was diabetic in the late 1980s, due to getting blood sugar readings approaching 140. That’s what the standard was for dx’ing diabetes then. It was later dropped to 125 or 126.
        I asked my current endo if he was one of the docs in the late 80s who wanted the standard for dx’ing diabetes dropped. He said, yes, that his trainer was very strict.
        He has an excellent grip on my endocrine misfires and all the unknowns about them. I noticed on my most recent blood work that my TSH approached 1.0 very closely. Some doctors might have adjusted it just because of that, but not him.

        • SarahJ89

          1.0 is perfect for me. I am absolutely terrified of every losing the RNNP who diagnosed and treated me. I don’t want to ever drop back into that abyss again. Sussing out a doctor is one of my main tasks when we go to Ireland this October. Our plan is to move permanently next winter. Fortunately, one branch of my family there is rife with nurses. One of them runs a pretty toney nursing home. My cousins were astonished to hear what I’d gone through. They’re all on levothyroxin because hypothyroidism runs in our family.

          I realize dogs and humans are different. But I have to say… all my dogs become hypothyroid as they age. My 12-year old Shelty just got diagnosed. It was a joy to watch her come back with tx.

          • querywoman

            They should be using the lab tests as guidelines and take symptoms into account as well.
            There are no lab guidelines for depression. They use depression as a dx too often for illnesses with vague symtoms or when they don’t know what you have.

          • SarahJ89

            Alas, they do not do that. The mighty THS score overrides any consideration of the many sxs of hypothyroidism. And once you are tagged with the mental health label of depression, good luck being treated as anything but a head case.

            Oddly, my chronic sinus condition and vasomotor rhinitis disappeared once my thyroid was treated. I haven’t had a sinus infection since. My theory is the rhinitis was caused by everything being slowed down. The resultant congestion created a perfect breeding ground for bacteria. I used to have nearly constant infections, especially in winter. I do not miss them.

          • querywoman

            Your previous tight-@$$ providers would say you simply get an emotional uplift thinking the levothyroxine helps you. As for your skin, they’d probably say you are using a moisturizer.
            But that doesn’t explain your cholesterol dropping and diminished infections!
            I’ll probably show our conversation to my current endo.

          • SarahJ89

            Yes. Fortunately my uplift has lasted four years and counting. Gotta love that placebo effect.

          • SarahJ89

            “They should be using the lab tests as guidelines and take symptoms into account as well.”
            Do you mind if I stitch this on a pillow? It would make a lovely gift for my doctor’s waiting room.

          • querywoman

            Heh! Why should I care?
            It appears you were always borderline in the past with symptoms clearly indicative of hypothyroidism.

          • SarahJ89

            Yes. Exactly 37 years ago a kindly doctor who was despised by his peers (he treated a lot of alcoholics, felt their addiction was somehow related to sugar metabolism–way ahead of his time) started to treat me. He told me “Your thyroid test is low normal but you have all the symptoms of hypothyroidism. I’d like to treat you to see if that helps.”

            Alas, the dear man died of a heart attack three weeks later. He is still remembered in our state, with a wing named after him in the hospital in his area. Some of his colleagues have actually caught up with his thinking, which is probably the best memorial he could ever have.

Most Popular