Stent Thrombosis Particularly Risky for Multivessel Disease

GRENOBLE, France, July 31 -- Drug-eluting stents appear to pose a particular risk for thrombosis in patients with diabetes and multivessel coronary disease, researchers here found.

In a large registry study, the one-year stent thrombosis rate among patients with diabetes was almost double the rate for nondiabetic patients with predominantly on-label use of the sirolimus-eluting Cypher stent (3.2% vs. 1.7%, P=0.03), said Jacques Machecourt, M.D., of CHU Grenoble, and colleagues.

Diabetic patients with multiple-vessel disease had an even higher 4.3% one-year rate (P=0.008), they reported in the Aug. 7 issue of the Journal of the American College of Cardiology.

Because about a quarter of the stent thrombosis cases occurred in the period after discontinuation of dual-antiplatelet therapy, the findings reinforce recommendations for longer drug therapy in these high-risk patients, the investigators said.

Label indications for Cypher stents recommend three months of clopidogrel (Plavix) plus aspirin.

But, professional associations have issued increasingly stern warnings that drug-eluting stents should be followed by 12 months of dual therapy, with an even longer course for diabetic and other high-risk patients.

(See: Stent Advisory Warns of Dire Cost of Early Halt to Antiplatelets and Alert Urges Lengthier Antiplatelet Use for High-Risk Drug-Eluting Stent Patients)

Prior analyses of drug-eluting stent registries have suggested that diabetes is a risk factor for stent thrombosis. Earlier studies of balloon angioplasty and bare-metal stents have also shown elevated mortality and stent thrombosis rates in diabetic patients.

Because of such safety concerns for real-world drug-eluting stent use, the researchers conducted the EVASTENT study. The ongoing independent registry includes all eligible patients with diabetes who have received Cypher stents at French university hospitals and high-volume community hospitals.

Only patients given stents on-label were considered eligible, but treatment for in-stent restenosis was permitted. In the end, only 19% of patients received a stent for off-label indications in the study. This proportion is much lower than the estimated 60% of patients who receive drug-eluting stents off label in the United States.

The researchers' analysis included consecutive eligible diabetic patients who were matched to a nondiabetic stent recipient for a total of 1,731 patients from January 2003 through November 2004.

The study required that patients receive 75 to 160 mg aspirin plus 75 mg clopidogrel daily for at least three months after stent placement. Thereafter, antiplatelet therapy was recommended but left to the physician's discretion.

Overall, 43% of patients had multivessel disease (356 diabetic patients and 374 nondiabetic patients). Nearly all patients (98.5%) had at least one year of follow-up.

At one year, the primary safety endpoint showed a significant disadvantage for patients with diabetes. The major adverse cardiac event rate (cardiovascular death, stent thrombosis, and acute MI) was 5.4% for diabetic patients compared with 2.7% for nondiabetic patients (P

Of the 45 cases of stent thrombosis, 23 occurred within 48 hours (acute) or 30 days (subacute) after stent implantation (1.9% in diabetic versus 0.8% in nondiabetic patients, P=0.04).

Among the late stent thrombosis cases, 11 occurred three to six months after implantation, five occurred from six months to one year, and four happened more than a year after implantation.

Likewise, 11 cases-24% of all stent thrombosis events in the study-were related to mismanagement of antithrombotic treatment. The researchers found:

• Two subacute stent thrombosis cases and six late stent thrombosis cases occurred within 10 days of complete withdrawal of the dual antiplatelet therapy.
• Two subacute cases were related to a clopidogrel administration delay after angioplasty.
• Two cases had documented aspirin or clopidogrel resistance.
• For 11 of 20 late stent thrombosis cases, interruption of dual antiplatelet therapy in favor of aspirin therapy alone was "noted or highly suspected" as the cause.

"In the light of our findings, it seems that some cases of stent thrombosis could be avoided by a better implementation of the antiplatelet regimen," the researchers said.

They suggested that better communication with patients and other physicians involved in their care "can prevent catastrophic cases related to complete withdrawal of dual antiplatelet therapy, particularly when noncardiac surgery is planned."

However, further study is needed to find the optimal duration of dual antiplatelet therapy, particularly for the high-risk diabetic population, and to demonstrate what the best therapeutic option is for diabetic patients with multivessel disease, they concluded.