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)