Drug-eluting stents for in-stent restenosis - ISAR-DESIRE

Nov 08, 2004
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Date Presented:
01/01/2004
Date Published:
01/01/2005
Date Updated:
11/08/2004
Original Posted Date:
11/08/2004
References

Description:

The goal of the ISAR-DESIRE trial was: 1) to evaluate the use of drug-eluting stents (DES) compared with balloon angioplasty for treatment of in-stent restenosis (ISR), and 2) to compare the drug-eluting sirolimus stent with the drug-eluting paclitaxel stent for treatment of ISR.

Study Design

Study Design:

Patients Enrolled: 300
Mean Follow Up: One year
Mean Patient Age: Mean age 64 years
Female: 22
Mean Ejection Fraction: Baseline ejection fraction 57%

Patient Populations:

ISR in a native artery

Exclusions:

Acute MI; left main disease; or allergy to sirolimus, paclitaxel, heparin, aspirin, or clopidogrel

Primary Endpoints:

Restenosis in-segment at six-month angiography, defined as stenosis ≥50%, for the comparison of stent groups with angioplasty group

Secondary Endpoints:

Net lumen gain at six-month angiography
Clinical event at nine months, including death, MI, and target vessel revascularization

Drug/Procedures Used:

Patients with ISR were randomized to either treatment with the sirolimus DES (n=100), paclitaxel DES (n=100), or balloon angioplasty (n=100). Patients underwent repeat angiography at six months and were followed for clinical events through 1 year.

Concomitant Medications:

Pretreatment with 600 mg clopidogrel for at least 2 hours

Principal Findings:

Postprocedure minimum lumen diameter was smaller in the balloon angioplasty group (2.07 mm) than the sirolimus DES group (2.5 mm) or paclitaxel DES group (2.6 mm; p<0.001). Almost half of the interventions were performed on the left anterior descending artery (45%). Repeat angiography at six months was performed in 92% of patients.

The primary endpoint of in-segment restenosis on six-month angiography was smaller in the DES groups than the balloon angioplasty groups (14.3% sirolimus DES, 21.7% paclitaxel DES, 44.6% balloon angioplasty; p<0.001 for sirolimus DES vs. angioplasty, p=0.001 for paclitaxel DES vs. angioplasty). Likewise, net lumen gain was larger in the DES groups than the balloon angioplasty groups (1.12 mm sirolimus DES, 1.02 mm paclitaxel DES, 0.41 mm balloon angioplasty; p<0.001 for sirolimus DES vs. angioplasty, p<0.001 for paclitaxel DES vs. angioplasty). Clinical target vessel revascularization occurred less often in the DES groups than the balloon angioplasty groups (8% sirolimus DES, 19% paclitaxel DES, 33% balloon angioplasty; p<0.001 for sirolimus DES vs. angioplasty, p=0.024 for paclitaxel DES vs. angioplasty). There was no difference in mortality (2% sirolimus DES, 1% paclitaxel DES, 3% balloon angioplasty) or MI by 1 year (1% sirolimus DES, 2% paclitaxel DES, 0% balloon angioplasty).

For the analysis comparing the two DES, in-segment late lumen loss was lower in the sirolimus DES group compared with the paclitaxel DES group (0.32 mm vs. 0.55 mm, p=0.02), as was in-stent late lumen loss (0.10 mm vs. 0.26 mm, p=0.004). Angiographic restenosis was directionally but nonsignificantly lower in the sirolimus DES group compared with the paclitaxel DES group (14% vs. 22%, p=0.19). Target vessel revascularization occurred less frequently in the sirolimus DES group compared with the paclitaxel DES group (8% vs. 19%, p=0.02).

Interpretation:

Among patients with ISR, treatment with DES was associated with a lower rate of restenosis compared with balloon angioplasty. Additionally, use of the sirolimus DES was associated with a lower target vessel revascularization rate and smaller late lumen loss than use of the paclitaxel DES in patients with in-stent restenosis.

The present trial is the first randomized direct comparison of the sirolimus DES versus paclitaxel DES. While the findings are provocative, larger studies are needed to validate the findings, given the small sample size. Additionally, the study was conducted in patients with ISR, not de novo lesions, and extrapolation to other populations may not be valid. The upcoming, much larger REALITY trial will compare the sirolimus versus paclitaxel DES in patients with de novo lesions. It should be noted that the ISAR-DESIRE trial was not an industry funded trial.

The other novel finding of the ISAR-DESIRE trial was the improvement in restenosis with use of DES over balloon angioplasty, the current primary treatment option for ISR. The presenter noted that while restenosis rates were lower with DES than with balloon angioplasty, the rate of restenosis was higher than in trials of DES in de novo lesions and hypothesized that a higher dose of drug may be needed for treatment of ISR.

References:

Kastrati A, et al. sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial. JAMA. 2005;293:165-171.

Kastrati A. ISAR-DESIRE: Drug-eluting stents for in-stent restenosis. Paper presented at the European Society of Cardiology Congress 2004, 29 August-1 September, Munich, Germany.

Keywords: Paclitaxel, Coronary Restenosis, Drug-Eluting Stents, Sirolimus


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