Sirolimus-Eluting Stent Compared With Paclitaxel-Eluting Stent for Coronary Revascularization - SIRTAX

Description:

The goal of the trial was to evaluate treatment with sirolimus-eluting stents compared with paclitaxel-eluting stents among patients with coronary artery disease, with no exclusions based on presenting syndrome or lesion site, complexity, or length.

Hypothesis:

Treatment with the sirolimus-eluting stent will be associated with a reduction in major adverse cardiac events (MACE) compared with paclitaxel-eluting stents among patients with coronary artery disease.

Study Design

Study Design:

Patients Enrolled: 1,012
Mean Follow Up: Five years (data reported through nine months)
Mean Patient Age: Mean age 62 years
Female: 23

Patient Populations:

Symptomatic coronary artery disease (stable angina, silent ischemia, or acute coronary syndrome), presence of at least one lesion covered with one or multiple stents of ≥50% stenosis, and anatomy suitable for coronary stenting

Primary Endpoints:

MACE at nine months; MACE was defined as cardiac death, MI, or target lesion revascularization.

Secondary Endpoints:

MACE at 30 days, six months, and years 1-5

Drug/Procedures Used:

Patients were randomized to stent implantation with either the sirolimus-eluting stent (n=503) or the paclitaxel-eluting stent (n=509). There were no restrictions on lesion site, number of lesions, lesion complexity, or length of lesions. In a prespecified manner, a subset of 600 patients underwent angiographic follow-up at eight months. The study was conducted at a single institution and was funded by the hospital; no industry funding was used for the study.

Concomitant Medications:

Aspirin (≥100 mg) and clopidogrel (300 mg loading dose and 75 mg/day); unfractionated heparin during the procedure

Principal Findings:

There were 1,401 treated lesions in the 1,012 patients, with an average of 1.2 stents used per lesion. Baseline clinical and angiographic characteristics were well matched between the treatment groups. Presenting syndrome was stable angina in 49% of patients and acute coronary syndromes in 51%, with 22% ST elevation myocardial infarction (MI). Device success occurred in 99% of patients.

The primary endpoint of MACE at nine months was lower in the sirolimus-eluting stent group versus the paclitaxel-eluting stent (6.2% vs. 10.8%, hazard ratio [HR] 0.56, 95% confidence interval 0.36-0.86, p=0.009). Individual components of nine-month MACE were death (1% vs. 2.2%, p=NS), MI (2.8% vs. 3.5%, p=0.148), and target lesion revascularization (4.8% vs. 8.3%, HR 0.56, p=0.03) for the sirolimus-eluting stent and paclitaxel-eluting stent groups, respectively.

The endpoint of target vessel failure was also lower in the sirolimus-eluting stent group (7.0% vs. 11.6%, p=0.01). Stent thrombosis did not differ by treatment group (2.0% for the sirolimus-eluting stent group and 1.6% for the paclitaxel-eluting stent group). Among the subgroup analysis, the treatment benefit in the primary endpoint for the sirolimus-eluting stent group was notably better in diabetics (HR 0.31, p=0.013) than the nondiabetics (HR 0.66, p=0.110).

Among the angiographic cohort, late lumen loss was lower in the sirolimus-eluting stent group compared with the paclitaxel-eluting stent group both in-stent (0.12 mm vs. 0.25 mm, p<0.001) and in-lesion (0.19 mm vs. 0.32 mm, p=0.001). Likewise, binary restenosis was also lower in the sirolimus-eluting stent group in-stent (3.2% vs. 7.5%, p=0.01 and in-lesion (6.6% vs. 11.7%, p=0.02).

Interpretation:

Among patients with coronary artery disease, treatment with the sirolimus-eluting stent was associated with a reduction in MACE at nine months compared to treatment with the paclitaxel-eluting stent, driven primarily by a reduction in the need for target lesion revascularization with a trend toward lower rates of MI and no difference in mortality.

The findings of the SIRTAX trial are discordant with the findings of the REALITY trial, which like SIRTAX, demonstrated improvements in the angiographic parameter of late lumen loss with sirolimus-eluting stents, but showed no difference in the primary endpoint of binary restenosis or in clinical MACE rates. Additionally, stent thrombosis was significantly higher in the paclitaxel-eluting stent group in the REALITY trial, while no difference in stent thrombosis was observed in the present SIRTAX trial.

While other trials such as ISAR DESIRE and ISAR DIABETES have compared the two drug-eluting stents in a head-to-head comparison for treatment of in-stent restenosis and in diabetics, respectively, the present trial along with the REALITY trial are the first large-scale randomized trials to evaluate the stents in a broader population of patients with coronary artery disease.

References:

Windecker S, et al. Sirolimus-Eluting and Paclitaxel-Eluting Stents for Coronary Revascularization. N Engl J Med 2005;353:653-62.

Presented by Dr. Stephan Windecker at the March 2005 ACC Annual Scientific Session, Orlando, FL.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), Interventions and ACS, Interventions and Coronary Artery Disease, Chronic Angina

Keywords: Paclitaxel, Coronary Artery Disease, Myocardial Infarction, Acute Coronary Syndrome, Follow-Up Studies, Angina, Stable, Thrombosis, Drug-Eluting Stents, Constriction, Pathologic, Confidence Intervals, Sirolimus, Diabetes Mellitus


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