What is the mechanism that allows patents with coronary stents to eventually stop taking Plavix?

Question

While the appropriate duration of anti-platlet or anti-coagulant therepy is currently being investicated (believed to be 6 months, a year or longer), it appears that the general theory is that it can eventually be stopped. Currently, it appears that it can be stopped sooner with bare metal stents than it can with drug eluding stents. What I would like to better understand is, why can it ever be stopped with either stent type. What happens to reduce the chance of clot formation after a year say, that allows Plavix to be discontinued? Is it that tissue grows over the stent? If so, then why go through the trouble of making drug eluding stents, which attempt to fight said tissue growth? Also, if tissue growth is bad, because it causes the vessel to close, then what happens when the drugs on the drug coated stents are used up? Do the drugs just delay the inevitable? If so, how long is the delay?

Thanks for the detailed reply. However, Taxus Express2 DES elude a drug specifically for slowing epitilialization! While I appreciate that there may be a need to minimize this process, so as not to allow too much growth into the vessel, it seems reckless to prevent such growth all together, thereby preventing full bio-compatibility.

If the plaque is soft enough that it can be pressed, like play-doh up against the artery wall, Why can't it simply be scrapped back into the catheter and removed.

Answer 1

-You got it right...let me explain. When the angioplasty is performed - essentially what happens is that a balloon simply crushes the flow limiting lesions (plaques - at least 70% blockage) out of the way. A stent is deployed and "sprung" into place, propping the vessel open. Now after you crush the plaque, this is very thrombogenic as a thrombus is part of the typical healing process (but definitely not too good in the middle of a large artery supplying your heart muscle with blood). The drug eluting stents (DES) are coated with medication that is anti-thrombotic and the Plavix assists the process.

At this point lets compare the bare metal stents - the Plavix of course prevents the thrombus here too. But why do you only need it for three months...because the healing occurs faster (because the healing process was not being inhibited at the site of the stent by the stent) After three months, all healed. The stents have been epithelialized and are now seamlessly part of the artery.

So I hear you asking - why did we ever use the DES in the first place? Because once the angioplasty is performed there is a very high risk period where a thrombus could form shortly after the procedure is performed - thus precipitating an acute event (a heart attack!). The DES have a substantially reduced episodes (roughly 30% for bare metal verses less than 10% for DES). Here's the rub - the DES stents often never epithelialize. That means that there's a rough, mesh, straw-like structure inside the artery forever. Anything that causes swirling or eddies in the blood stream can also be thrombogenic too - hence the recommendation for continued use of Plavix indefinitely in some cases.

We risk stratify based on a few things -
*the length of the stent or stents deployed consecutively
*the location of the stent (high risk verses moderate or low risk)
*the baseline risk for a patient being hypercoagulable in the first place - e.g. smoker, hypertensive, cancer, etc.
*Pateint preference.

Our understanding of this is a best guess at this point. We hope to have some clinical trials to guide us more definitively on all of this some time in the future.

The original flow-limiting lesions are plaques are not the simple intimal lining found in healthy arteries - so having the "skin" that grows over the stents is not at risk for over growth and causing blockage again. The enemy is the plaque.

With our current understanding, these plaques grow through having excess cholesterol and triglycerides in our system. There are some great studies that show with agressive control (always through use of high dose medications, like statins) of cholesterol the plaques can be stablized and in fact reduced. (see the HATS and ARBITOR2 studies)

Not all patients follow our advice, however. They continue to smoke, have poorly controlled hypertension, diabetes, and high cholesterol - which, you guessed it, can result in "in-stent restenosis." This has nothing to do with the thrombogenesis or Plavix we discussed above.

I hope this has answered your questions and helps.
Good luck.

Addendum - I am not sure how you invent a stent that attempts to prevent a biological response entirely - clotting - but then does not affect epithelialization. When first introduced it was thought that once the drug stopped being eluting - about six to nine months, that epithelialization would occur then...and it may in some people. But in others, the show is over and no additional healing occurs...the stent remains pressed in the arterial wall. Really this idea that the intimal lining over-grows and is responsible for stenosis is just not the case.

I understand that there is work being done on a magnesium stent that will actually might dissolve over time - interesting. Also, I am sure, full of potential unforeseen consequences.

The pressures used to clear stenosis is 3 atmospheres; which is significant - it is a misnomer to think of the plaques like Play-dough. It is called angioplasty, afterall - material is moved - 70% or greater blockage (often near totally occluded) to usually to 0%.

"Digging" the material out would in no way change everything we just discussed and we would be back to the days of - no stents - which resulted in frequent thrombosis and restenosis at the same spot. (aka the Halcyon Days for interventionalist cardiologists)

There are "cutting balloons" that are sometimes used to clear severely calcified plaques (have their own risk of embolization - even though a screen is deployed downstream from the procedure).

I hope that answered your questions - and I hope at this point that I have earned my 10 points (uncramping my typing fingers-whew) have a good day, my friend.

Answer 2

Your pharmacist and DR can help you with these questions far better than anyone on here. Good luck!
http://www.rxcarecanada.com/Plavix.asp?prodid=1363
http://www.plavix.com/plavix/hcp/channels/content.jsp?BV_UseBVCookie=Yes&channelId=-1073752565
http://products.sanofi-aventis.us/plavix/plavix.pdf