From the annual meeting of the American College of Cardiology in Atlanta
The black box warning that the FDA slapped onto its labeling for the antiplatelet drug clopidogrel (Plavix) on March 12 became the talk of the American College of Cardiology’s annual meeting when it started a couple of days later. It also abruptly changed medicine’s antiplatelet playing field.
Cardiologists, as well as primary care physicians, prescribe clopidogrel, often with aspirin, to many patients with coronary disease to help keep blood clots from forming inside their arteries.
The FDA said it decided to impose the boxed warning because anywhere from 2%-14% of people are “poor metabolizers” of clopidogrel, which makes them unable to effectively convert it into its active form. In other words, when a poor metabolizer receives clopidogrel it’s as if the drug were never administered, because the person cannot change the drug to make it active.
The implications of the FDA’s action were clear to many physicians at the ACC meeting. They now had three options for dealing with patients who needed antiplatelet therapy. They could:
1. Treat patients with clopidogrel and then test their platelets’ reactivity to see if it had been properly blunted by clopidogrel treatment. If not, switch to a different drug.
2. Test each patient before starting clopidogrel to see if they carried a mutation in one or both of their genes for the liver enzyme (cytochrome P2C19) responsible for producing the active metabolite of clopidogrel. If they carried a mutation, switch to a different drug.
3. Skip either test and jump straight to an alternative drug. The most obvious alternative right now is prasugrel (Effient), an agent that’s very similar to cloipidogrel except it does not require enzymatic activation.
What the FDA’s action precluded was maintaining the status quo. By adding the black box warning to clopidogrel last week, the FDA eliminated prescribing clopidogrel blindly as standard of care.
—Mitchel Zoler (on Twitter @mitchelzoler)