Anti-restenotic efficacy of SES is non-superior to PES in patients with SES-restenosis: Results of the ISAR-DESIRE 2 Trial

September 24, 2009 By Alexandra M. Palmer [mailto:apalmer@perfuse.org]

San Francisco, California: Results from the ISAR-DESIRE 2 trial indicate that repeat Drug-Eluting Stent (DES) implantation for DES-restenosis is safe out to 1 year. In cases of Sirolimus-Eluting Stent (SES)-restenosis, SES and Paclitaxel-Eluting Stents (PES) are associated with a comparable degree of anti-restenotic efficacy. This report was presented by Robert Byrne at the Transcatheter Cardiovascular Therapeutics Conference 2009.

Introduction and Objective
Since its inception, DES therapy has become commonplace in the treatment of coronary artery disease patients. Along with the increased use of DES, the number of patients presenting with DES-restenosis has also risen. In the United States alone, an estimated 200,000 cases occur each year. The optimal treatment strategy for in-stent restenosis is to maximize acute gain while minimizing late loss. In Bare-Metal Stent (BMS)-restenosis, DES accomplish this. However, the most effective treatment strategy for DES-restenosis is unclear. Implanting another DES is the preferred solution, but there is no data supporting use of a different DES (“hetero-DES”) or the same DES (“homo-DES”). Two types of DES are SES and PES. Previous studies have demonstrated superiority of SES over PES in subsets of patients with high-risk features, but the comparative performance of both stents in SES-restenosis has not been investigated.

The objective of ISAR-DESIRE 2 was to compare the anti-restenotic efficacy of SES versus PES in patients with SES-restenosis. The SES and PES stents used were Cypher and Taxus, respectively.

Methods and Inclusion/Exclusion Criteria
The ISAR DESIRE 2 trial was a randomized, open-label, active-control trial involving 450 patients enrolled at two centers in Munich, Germany. Inclusion criteria required in-SES restenosis >50% and signs/symptoms of ischemia. Patients were excluded if they presented with cardiogenic shock, a lesion in LMCA or graft and/or acute myocardial infarction.

Half of the enrollment population (n=225) was randomized to SES and the other half (n=225) was randomized to PES implantation. Both groups received an angiographic follow-up at 6-8 months and a clinical follow-up at 12 months.

Baseline Characteristics
Baseline characteristics were similar between the two groups:
 * Mean age was 66-67 years


 * About 35% of patients were diabetic


 * 80% of patients presented with stable angina, while 20% presented with ACS


 * Vessel size was about 2.3-3.25 mm in both groups and lesion length was 4-21 mm


 * Restenosis morphology: diffuse (30% SES, 35.8% PES), occlusive (4.9% SES, 3.3% PES)

Results
Compared to SES, PES was associated with similar rates of primary, secondary and safety endpoint measures as well as similar occurrences of Major Adverse Cardiac Events (MACE).

30-day results There was no significant difference in the rates of death, MI, and death/MI/TLR composite between patients treated with SES and those treated with PES at 30 days. Rates were below 2% for both groups. Additionally, there was no occurrence of stent thrombosis and no need for Target Lesion Revascularization (TLR) in either treatment arm at 30 days.

Primary Endpoint Results: Late Luminal Loss There was no significant difference in the pre-specified primary endpoint of in-stent late luminal loss between the two treatment groups (SES 0.40 mm, PES 0.38 mm, p=0.75).

Secondary Endpoint Results: Binary Restenosis The occurrence of in-segment restenosis was similar between the two study arms (SES 19.0%, PES 20.6%, p=0.69).

Secondary Endpoint Results: Target Lesion Revascularization The rate of TLR was also similar between the two arms (SES 16.6%, PES 14.6%, p=0.52).

Safety Endpoint Results: Death, MI, or Stent Thrombosis Rates of death, MI or stent thrombosis were statistically the same for SES and PES (SES 6.1%, PES 6.3%, p=0.98).

Major Adverse Cardiac Events Occurance: Death, MI or TLR The difference in the occurrence of the major adverse cardiac events death, MI or TLR was not statistically significant between the two groups (SES 20.4%, PES 19.6%, p=0.71).

Conclusions, Discussion, Interpretation
The above results indicate that repeat DES implantation for DES-restenosis is safe out to 1 year. In cases of SES-restenosis specifically, both SES and PES are associated with a comparable degree of anti-restenotic efficacy. The data collected demonstrates that in patients previously treated with a SES, implantation of the same DES (SES) versus treatment with a different one (PES) yields comparable results in preventing restenosis.

Since it is now known that DES implantation for DES-restenosis is safe out to 1 year and that SES and PES are equally effective in preventing further restenosis, it is highly probable that the results from ISAR-DESIRE 2 will have an effect on clinical practice- specifically in the treatment of patients who experience restenosis after implantation with a SES. However, the fact that strict enrollment criteria are used in clinical trials must still be taken into consideration. The results observed here may not be applicable to all patients in clinical practice. Furthermore, the sample size was small and may have limited the statistical power. Additionally, the study population was limited to two centers in a single country. Further investigation could include the effect of SES and PES treatment on restenosis in patients previously treated with PES.

Sponsorship
ISAR-DESIRE 2 was sponsored by Deutsches Herzzentrum Muenchen.

ClinicalTrials.gov Number
NCT00598715

PowerPoint Presentation
[[Media:20090923_TCT Main_DESIRE-2_Concise.ppt]]