GETTING TO THE HEART OF ENHANCED CLAIMS

The recent controversy about the ENHANCE study is an important illustration of a serious and long-standing problem with the medical profession, and its allied siblings.

What is the ENHANCE study all about? Surely not a penis-enlargement issue, my readers may be forgiven for wondering even fleetingly. Well, it is a study on two treatment modalities for patients with high lipid (cholesterol, for example) levels. But, first, the basics.

You may have high lipid levels because of genetic reasons, or because you eat, drink, or smoke too much. Many of us are obese, too. Traditionally, if you have high cholesterol, apart from the usually discarded ‘lose weight-do exercise’ kind of advice to the patient, your doctor would give you drugs. These lipid-lowering drugs are called, broadly, statins. One of the most common ones today is Lipitor (atorvastatin).

Why is it important to lower cholesterol? Because high cholesterol can lead to fatty plaques being deposited in the coronary arteries (atherosclerosis), leading to a heart attack.

Statins are prescribed to millions of patients around the world, including those with heart disease, hypertension and diabetes (conditions commonly associated with high lipid levels). All statins act by blocking a liver enzyme that normally results in the formation of cholesterol.

The problems with statins are mostly with their cost and side effects. In addition, in a number of patients, they don’t work well enough. Increasing the dose may increase the side effects. So, what can your doctor do in this kind of scenario?

Enter Ezetimibe. This drug reduces the absorption of cholesterol from the intestines, which bear the brunt of all the cholesterol-rich good things in life that the mouth (along with the mind it carries) chases relentlessly.

With me so far?

So, you have statins that reduce cholesterol, and you have ezetimibe, that also does the same in a different way. Why not combine the two? Will surely work better, and reduce the fatty deposits in your coronary arteries, logically. Merck did that in collaboration with Schering-Plough, with Zetia (ezemitibe) and Vytorin (a $5 billion product).
A 30-day course of Vytorin costs around $100, while Zetia costs $93, compared to $32 for a course of generic simvastatin.

That is what the ENHANCE trial was supposed to prove. Unfortunately, it did not show any such benefit.

However, some experts are discounting the trial, saying it is not a fair representation of the truth, that it is botched, and that they would wait for further trials before changing their prescriptions away from Zetia. Around 60% of doctors, however, are likely to stop prescribing the drug. Obviously, it would be a catastrophe for the company, reeling as it still is from the Vioxx losses. Merck stocks have slid down after this trial has come to light.

The important issue that has come up again in this debate is captured in two quotes:

The main problem is that after six years on the market, there are no data for ezetimibe demonstrating any health outcome benefit. In the absence of any demonstrable effect beyond LDL lowering, nearly one million prescriptions per week are written for ezetimibe. Is this rational?

If the ENHANCE trial had shown regression of atherosclerosis or slowed progression, both the company and advocates of ezetimibe would be trumpeting the results as a landmark study. Now that the trial has failed, they describe ENHANCE as a small and unimportant imaging study. You can’t have it both ways!

THAT, ladies and gentlemen, captures a huge truth. Much of what we do as doctors stems from trials that prove one or the other. Products become available commercially, too, and we are tempted or habituated to use them, especially if treated well at cruises and exotic junkets. However, as clinicians, we would still want to do better for the patient, and refine our treatment methods as evidence improves. Therefore, it is vital that we know which data is proven, and which is putative, suggestive or alleged.

That, however, is a tall order!

(Sources: Heartwire and Medscape)

7 responses to “GETTING TO THE HEART OF ENHANCED CLAIMS

  1. “Much of what we do as doctors stems from trials that prove one or the other. Products become available commercially, too, and we are tempted or habituated to use them, especially if treated well at cruises and exotic junkets.”

    This is precisely why I insist that I’d rather die of the disease than the side effects of medicines intending to cure the primary ailment. Isn’t it true that with allopathy does not treat your problem as a specific one and does not treat your condition holistically but gives you a general drug available in the market thereby reducing you to a statistic?
    I know that there are many good doctors who want to help us feel better but all I am saying is that you are not being helped by your pharamcological colleagues in this endeavour or perhaps this is a defect in this system of medicine itself.

  2. That’s the reason why one should take drugs only as a last resort. There are side-effects to everything and I believe there are side-effects to those drugs which the medics say have no side-effects!

  3. R-Doc: Don’t statins also resemble Hotel California in some way? As in, once you are on them, you cannot just stop – it is a lifelong commitment?

  4. “This is precisely why I insist that I’d rather die of the disease than the side effects of medicines intending to cure the primary ailment. ”
    Usha: That is throwing the baby out with the bathwater. Sounds crazy to me!

    Nita: One should not, in the absence of specialised knowledge tinker with health. If sceptical, one should question one’s doctor and clarify the issues. No one says medicines have NO side effects.

    Shefaly: Yes. Like drugs for thyroid, hypertension, diabetes, and many more.

  5. I am an advocate of allopathy. While allopathy is, imho, pathetic when it comes to prevention, it is the best cure yet.
    Any food has side effects – as they say in Tamil, alavukku minjinaal amirthamum nanju. The side effects don’t necessarily kill. Would you much rather have your loved one die of, say, cancer, than let them lose some hair and appetite for a few months with chemo?
    But that is a digression from the main issue. It takes a few or many years for studies to conclusively prove the efficacy of any drug. The see-saw of Asprin is a proof. All we can hope for is that multinationals do not doctor (pun unintended) research results to suit their commercial needs.

  6. Lakshmi:
    Yes, I agree. The need to manipulate data for commercial reasons is, alas, an old malady. It is the dark lining around the silver cloud.

  7. Enjoyed the article, doc. Many people have no idea how evolving and dynamic medicine really is. And how studies can be manipulated when the profit motive or investment is large.

    With its cash-cow Lipitor soon to lose its proprietary status, look for a me-too drug from Pfizer. I do feel sorry for clinicians who have to keep up with so many new drugs and who have to wade through studies, which may or may not be well-done.
    Part of the cost of living longer, healthier lives.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s