Plavix, the Cardiac Perfect Storm

Plavix, the Cardiac Perfect Storm
Fran Van Cleave 
Date: 0000-00-00
Subject: Drugs and Medications

The popular drug Plavix is an anti-clotting agent frequently used in treating acute coronary syndrome (ACS), a medical term for any group of symptoms caused by obstruction of the arteries of the heart, such as a heart attack. The drug is also used on a long-term basis after the placement of mesh tubes called stents " most often in the heart " in order to prevent the build-up of plaque that, like silt in plumbing, would restrict the flow of blood. Plavix is also used to treat  the most common of the two types of stroke, in which blood clots or blobs of fatty plaque are flipped off the wall of an artery into the brain.

In March 2010, the FDA placed a “black box” warning " its most serious warning " on Plavix to make healthcare providers aware that up to 14% of patients are at high risk of treatment failure because they are poor metabolizers of this drug. You see, Plavix is no more active than a sugar pill when swallowed, and becomes active only when a liver enzyme converts it.

New concerns have now been raised, because not only did the FDA grossly underestimate how many people have the genetic variant with the inactive form of the converter enzyme, it seems both the regulatory agency and the drug company, Bristol-Myers Squibb, ignored another common problem: an interaction with any of the proton-pump inhibitor class of drugs in patients taking Plavix.

How big a problem is this? Sales of proton-pump inhibitors in the U.S. hit $14 billion in 2012. Over the past 11 years, sales of brand and generic Plavix have reached $73 billion. Even for expensive medications, that’s an awful lot of prescriptions. But then, there’s a big patient population to draw on. According to the CDC, every year about 715,000 Americans have a heart attack. Over 800,000 of us die every year from heart disease and strokes. That’s nearly one-third of deaths in this country.
As it turns out, this inability to metabolize Plavix is a very common genetic variant, occurring in 30% of individuals of European ancestry, 40% of African ancestry, and more than 50% of Asian ancestry. According to The Lancet, the most prestigious medical journal in the world, patients with one of these variants are 1.5 to 3.5 times more likely to die or have complications than patients with the high-functioning gene. Study results published in the March 4, 2009 issue of the Journal of the American Medical Association show that patients who took Plavix and a PPI together were more likely those who took Plavix alone to either die or be rehospitalized for a heart problem. Or to need another surgery to reopen a coronary artery.

There is an alternative: a drug called Brilinta, like Plavix but already in the active form. Trouble is, it causes more bleeding than Plavix, which has killed quite a few people with brain hemorrhages, so it’s riskier than the standard treatment for ordinary patients. But for non-metabolizers, that risk pales by comparison to being treated with a drug that does nothing. Complicating the issue is the fact that Brilinta is too new to be available as a generic. Hospitals are cutting costs wherever they can, which frequently means cutting drug inventory to the least expensive and most frequently used drug in any category. That means the vast majority of hospitals only carry generic Plavix. Given the economy, hardly anything could be more predictable.

Since the FDA put out its black box warning on Plavix, research has shown that nearly three times as many patients as they had estimated can’t metabolize the drug, and that the risk these patients face is much worse than they thought. Yet patients are still routinely treated with Plavix without screening to determine whether or not they will respond to it, and when they don’t respond, it is often too late for another treatment to save them (some ER doctors have tried doubling the dose in case of uncertainty, which has not worked). 

But there’s good news for potential victims of the Plavix standard. Screening for ability to metabolize the drug is now readily available, relatively quick, and cheap. Soon, perhaps, hospital labs may be able to run the test before a treatment decision must be finalized. For now, individuals can take matters into their own hands by taking advantage of remarkably inexpensive and informative genetic screening on their own, in advance of any emergency. At 23andme.com, for example, for $99 you can spit in a tube, send it in, and in a few weeks know your genetically predictable level of response to a number of common drugs, as well as how susceptible you should be to side effects. You also learn (if you wish) your relative odds of developing such life-shattering diseases such as diabetes, Parkinson’s Disease, and Alzheimer’s, among others " and with that information, adopt lifestyle changes that can tilt the odds in your favor. For the purposes of this article, patients can at last be prepared when they find themselves in the ER to tell their doctors that Plavix won’t work for them and they must be given Brilinta instead. That ability could save many, many lives.

Today’s inexpensive genetic screening will mean the end of one-size-fits-all medicine. Pressure will be on hospitals to provide genetic screening before committing patients to a particular regimen (which will require major changes to medical records-keeping due to the size of the files, so don’t expect it to happen overnight). But it’s clear the FDA dropped the ball on this one three years ago. The agency fines drug companies billions of dollars for poor judgment and bad science. By rights, it should be held accountable for creating this disaster for so many of America’s families … but at the very least it should be expected to require due diligence on the part of medical providers in avoiding what are now scientifically predictable tragedies.

Scary to look at your own genetics? Yes. Too much information? No. It’s a lot easier to watch a video on your genetic results and talk to your doctor about it than wait for the FDA to get off the dime.