Late Clinical Events Related to Late Stent Thrombosis After Stopping Clopidogrel - BASKET LATE

Description:

The goal of the trial was to evaluate late thrombotic events among patients treated with drug eluting stents vs bare metal stents after clopidogrel discontinuation.

Study Design

Study Design:

Patients Enrolled: 746
Mean Follow Up: 18 months
Mean Patient Age: Mean age 63.6 years
Female: 21

Patient Populations:

All patients undergoing PCI irrespective of indication for PCI

Exclusions:

Target vessel diameter ≥4 mm, restenotic lesions, or an event during the on-clopidogrel phase

Primary Endpoints:

Cardiac death or MI at one year following clopidogrel discontinuation

Drug/Procedures Used:

Patients were randomized in a 1:1:1 strategy to paclitaxel-eluting stents, sirolimus-eluting stent, or bare metal stent. All patients were treated with clopidogrel for 6 months. The main trial evaluated the cost effectiveness of drug-eluting stents vs bare metal stents. The present study evaluated late thrombotic events in the year following discontinuation of clopidogrel therapy. The present analysis pooled the drug-eluting stent patients (n=499) vs the bare metal stents patients (n=244), excluding patients who had an event prior to the end of clopdigrel. There was no planned angiographic follow-up, although angiograms were evaluated when available when a clinical event occurred.

Concomitant Medications:

Aspirin indefinitely

Principal Findings:

The study population was comprised of 21% ST elevation MI patients, 37% unstable angina, and 42% stable angina. Multivessel disease was present in 67%, and the culprit artery was the left anterior descending in 51% of patients. An average of 1.9 stents was used per patient.

In the year following clopidogrel discontinuation, the primary composite endpoint of cardiac death or MI occurred significantly more frequently in the drug-eluting stent group (4.9% vs 1.3%, p=0.01). Non-fatal MI was also higher in the drug-eluting stent group (4.1% vs 1.3%, p=0.04) and cardiac death trended higher (1.2% vs 0%, p=0.09). There was no difference in restenosis driven target vessel revascularization (4.5% vs 6.7%, p=0.21). Late stent thrombosis (combination of angiographic document thrombosis and thrombotic clinical events) occurred in 2.6% of the drug-eluting stent group and 1.3% of the bare metal stent group (p=0.23). The median time of the late thrombotic event was 116 days following clopidogrel discontinuation, but events occurred throughout the one year follow-up (range 15 to 362 days).

Interpretation:

Among patients with coronary artery disease treated with PCI, use of a drug-eluting stent was associated with significantly higher rates of cardiac death or MI compared with bare metal stents in the year following clopidogrel discontinuation.

Many trials have demonstrated a reduction in target lesion revascularization with drug-eluting stents compared with bare metal stents in recent years, but none has ever demonstrated an effect on the hard endpoints of death or MI. Restenosis, while not desirable, is not an independent correlate of subsequent mortality. The present study showed a more than three-fold increase in death or MI with drug-eluting stents in the year after clopidogrel discontinuation. Late stent thrombosis is a serious and often fatal complication. Clopidogrel is generally prescribed for the first 6 months following stent placement, along with aspirin indefinitely. These data suggest the 6 month anti-platelet regimen of clopidogrel may not be long enough to provide adequate protection from late thrombosis with drug-eluting stents. It is unknown if a better strategy would be a longer duration of clopidogrel, a more potent anti-platelet drug, or a different drug-elution or kinetic pattern on the stents. The authors noted that for every 100 patients treated with a drug-eluting stent, 3.3 cases of cardiac death or MI are induced for a reduction of 5 cases of target lesion revascularization. Further study on late thrombotic events with drug-eluting stents is strongly warranted given these findings.

References:

Pfisterer M, et al. Late Clinical Events After Clopidogrel Discontinuation May Limit the Benefit of Drug-Eluting Stents. J Am Coll Cardiol 2006;48:2584-91.

Presented by Dr. Matthias E. Pfisterer at the March 2006 ACC Annual Scientific Session, Atlanta, GA.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease

Keywords: Cost-Benefit Analysis, Follow-Up Studies, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Ticlopidine, Sirolimus, Angioplasty, Balloon, Coronary, Stents, Paclitaxel, Metals, Coronary Thrombosis


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