Are You Getting The Protection You Need From Plavix?

By: David A Fein, MD
Medical Director

The blood thinner Plavix (clopidogrel) is often prescribed for people who are considered at high risk for heart attacks or strokes or have a stent in their coronary arteries. On March 12, 2010, the Food and Drug Administration (FDA) issued a Safety Announcement concerning Plavix. The warning comes because as many as 14% of those given Plavix may not be get the expected level of protection from the drug.

Plavix helps to prevent heart attacks and strokes by inhibiting the activity of platelets, a component of blood responsible for forming clots. Most heart attacks occur because of the formation of a blood clot inside an artery. This is usually a result of a phenomenon doctors refer to as plaque rupture.

Over a period of years cholesterol and other substances are gradually deposited in the walls of the arteries. This process, called atherosclerosis, creates a thickened area in the artery wall often simply called plaque. Most plaque does not cause any significant narrowing of the inside, or lumen, of the artery where the blood flows. The artery actually expands to accommodate the thickening of the wall without impeding blood flow.

Coronary Artery Plaque

The contents of the plaque are separated from the blood flow within the lumen by a thin membrane. As the plaque enlarges, or if inflammation within the plaque causes that membrane to become too thin, that thin barrier between the inside of the plaque and the lumen can split open. That is plaque rupture. When the plaque ruptures it exposes the contents of the plaque to the bloodstream. Some of those substances inside the plaque activate the platelets that are passing by and start the process of clot formation. Once this happens, an artery that had an asymptomatic, non-obstructive plaque for many years can become completely blocked by a blood clot within just minutes.

If the blood clot completely obstructs the artery, the portion of the heart muscle down the length of that artery starts to die and a heart attack occurs.

If a clot forms from plaque rupture in one of the arteries to the brain the result can be a stroke.

In some cases, the plaque has progressed to the point where the artery can no longer continue to expand enough to accommodate the plaque and maintain an adequate lumen. If the lumen becomes narrowed by more than about 70% a stent, which is basically a spring-like metal cage, may be placed in the artery to help hold it open. However, the stent itself can cause blood clots to form, blocking the stent and stopping blood flow. This can occur months, or even years, after the stent is placed.

Medications such as aspirin and plavix help to prevent heart attacks and strokes by interfering with the ability of the platelets to form blood clots. When plaque rupture occurs the medication helps to limit the size of the clot, hopefully allowing just a big enough clot to seal the rupture but not a big enough clot to completely block the artery. Overall, these medications can reduce the risk of heart attacks and strokes by 35% or more.

Nearly one quarter of people who take aspirin for heart attack prevention turn out to be resistant to its blood thinning effects. (See our newsletter on Aspirin Resistance) Fortunately, this can be detected with a simple urine test. Those who are resistant to aspirin are usually advised to try a higher dose or switch to Plavix.

The FDA’s warnings stem from the way that Plavix works in the body. Plavix is actually a “pro-drug”. That means that the medication in the tablet is not the active form of the drug. It must first be converted, or “metabolized”, in the liver into the form of the drug that actually affects platelet function. This is done by an enzyme in the liver known as CYP2C19. The problem is that some people have a variation of this enzyme that is much less effective, or not effective at all, in metabolizing Plavix into its active form. Which type of the CYP2C19 enzyme you have is genetically determined. Estimates range from 2% to 14% of the population having a form of the enzyme that is so ineffective at converting Plavix into the active metabolite that they get little or no protection from the medication.

A simple test is available to determine whether you have a form of the enzyme that will not adequately process Plavix into its active form. With either a small blood sample or a swab from the inside of the cheek a DNA analysis determines which genetic type you have and, therefore, which form of the enzyme you make. If you have a variation of the enzyme that does not metabolize Plavix effectively your doctor may need to increase your dose or consider using other medications to help protect you against blood clots in your arteries or stent. We recommend that every patient who is currently taking Plavix to help reduce their cardiovascular risk should have this test done.

Other medications that you may be taking can also interfere with the ability of the enzyme to convert Plavix to its active form. In November, 2009, the FDA issued a warning that Prilosec (omeprazole) commonly taken to reduce stomach acidity, could block the CYP2C19 enzyme and render Plavix ineffective. Many other medications may have the same effect. If you are taking any other medications with Plavix you should check with your doctor or pharmacist about potential drug interactions.