Stents and Clopidogrel (Plavix): When and How Long? Evidence for the Long Term Use of Clopidogrel

There are two things to consider when prescribing clopidogrel post-stent placement.  One is the prevention of major adverse cardiac events post-procedure, and the second is the prevention of subacute thrombosis. In 2001, the results of the landmark CURE trial (Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events), published in the New England Journal of Medicine and the Lancet, demonstrate that initiating therapy with clopidogrel early, and continuing its use long-term, dramatically reduces the risk of heart attack, stroke and cardiovascular death by 20% in patients with acute coronary syndrome (p < 0.001). The companion study, PCI-CURE, published in the Lancet, showed that if patients undergo percutaneous coronary intervention, there are huge benefits with clopidogrel treatment given prior to the procedure and when continued up to one year after angioplasty. In those patients, overall, there was a 31% reduction in overall cardiovascular death or myocardial infarction (p = 0.002).

Era of Drug Eluting Stents

The addition of drug eluting stents (DES) to the therapeutic armamentarium has changed the face of interventional procedures and patient outcomes since their approval.  The CYPHER* sirolimus-eluting stent was approved for use in 2003, and the TAXUS* paclitaxel-eluting stent was approved in 2004.  Each of the DES inhibits cellular proliferation, decreasing the risk of restenosis; however, the mechanism of the two stents is quite different.  Sirolimus is an immuno-suppressant known for its antiproliferation properties, while paclitaxel is a chemotherapeutic agent which stabilizes microtubules causing cells to stop dividing due to a mitotic block between metaphase and anaphase of cell division. Paclitaxel also inhibits various growth factors that prevent smooth muscle cell migration.  Thus the length of time for stent endothelialization varies, as does the requirement for anti-platelet therapy with clopidogrel.

Cordis and Boston Scientific, the manufacturers of the CYPHER* and TAXUS* respectively, in conjunction with the FDA Circulatory System Devices Panel have advised that all patients receiving drug eluting stents follow a prolonged administration of clopidogrel post-procedure to prevent subacute stent thrombosis.  Specifically,

CYPHER®  DES requires a minimum of 3 months of clopidogrel, with aspirin maintained indefinitely. 
TAXUS®  DES requires a minimum of 6 months of clopidogrel, with aspirin maintained indefinitely. 

Bare metal stents require a minimum of 4 weeks of clopidogrel, with aspirin maintained indefinitely.  In an emergent situation, clopidogrel may be reduced to a minimum of 2 weeks.  If you are considering the cessation of aspirin, clopidogrel (or ticlopidine) due to some adverse reaction or medical event, please contact the Interventionalist, to reduce the potential risk of complications.  Premature cessation of Plavix (or Ticlid) may leads to subacute thrombosis, acute myocardial infarction, and death.