Should U.S. Adopt European Clopidogrel Dosing Standards?
Two clinicians presented opposing views on this issue in the TCT Debate of the Day.
The TCT Debate of the Day on Monday focused on whether drug-eluting stents should be used more conservatively due to increased safety concerns and whether the European practice of extended, post-procedure clopidogrel therapy should be considered by U.S. surgeons.
In this discussion, David P. Faxon, MD, argued that the use of drug-eluting stents should be curtailed while Sigmund Silber, MD, countered that drug-eluting stents remain an important innovation.
“There’s probably been no subject in interventional cardiology that has been more hyped than this, or more controversial,” Faxon said. “Hopefully we will shed a little bit of light on this important topic.”
Need for caution
Faxon discussed delayed healing and late stent thrombosis associated with drug-eluting stents, as well as the effect of drug-eluting stents on negative remodeling. He cited a study looking at events following subacute stent thrombosis in 2,512 consecutive patients. The events included death in 32% of patients, myocardial infarction (MI) in 53% and angina in 15%.
Faxon cited a study that indicated that drug-eluting stents provide incomplete neointimal coverage after three to six months. “It appears that incomplete coverage was the norm with the drug-eluting stents, whereas complete coverage was the norm with bare-metal stents. Complete coverage is achieved within a month or so for the vast majority of bare-metal stent patients.”
The BASKET-LATE trial demonstrated a significant increase in MI and death in the drug-eluting stent group. Noncardiac mortality was confined to patients with cancer.
Late and very late stent thromboses are increased with drug-eluting stents by 0.2% to 0.6%, respectively, per year, Faxon said.
Faxon said that drug-eluting stents should be avoided in patients who are unable or unwilling to use dual antiplatelet therapy.
An important innovation
Silber discussed the differences in guidelines for using clopidogrel with drug-eluting stents in Europe compared with those in the United States. He said patients should be given clopidogrel for at least six months after a drug-eluting stent; the U.S. recommendation is three months. By extending the duration of clopidogrel therapy, Silber suggests that clotting risk can be minimized.
”I was surprised to see how short a time patients have clopidogrel after drug-eluting stents,” he said. “I’m quite sure that Americans will need to rewrite their guidelines with a longer duration of clopidogrel.”
In discussing the BASKET LATE trial, Silber said he felt the study was “unethical to withdraw clopidogrel after six months.” Silber maintained that the average stent thrombosis rate for bare-metal stents is not necessarily low at the three- to four-month mark (Figure).
Silber also addressed the noncardiac mortality rates among patients with cancer who received a drug-eluting stent, pointing out that the cancer was a pre-existing condition. “How can you say this was due to the stent if [cancer] was already present?” he said.
Drug-eluting stents are an important innovation, Silber said, with 46% of their use in the United States off-label. He emphasized that bare-metal stents also show late stent thrombosis and recommended a longer duration of clopidogrel in conjunction with their use, as well.
Newer and better drug-eluting stents may need to be developed, but the innovation is too valuable to curtail, he noted. “Don’t throw away the baby with the bathwater,” he said.