Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis: 3 Treatment Approaches | Clinical Trial - ISAR-DESIRE 3

Description:

The optimal treatment of drug-eluting stent (DES) in-stent restenosis (ISR) is not well established. The current trial sought to compare three different strategies for the treatment of DES ISR: 1) treatment with paclitaxel-eluting balloon (PEB), 2) paclitaxel-eluting stent (PES), or 3) balloon angioplasty alone.

Contribution to the Literature: The ISAR-DESIRE 3 trial showed that paclitaxel-coated balloons have similar repeat revascularization rates as PES, but lower than balloon angioplasty alone in patients with ISR in an existing DES.

Hypothesis:

Study Design

  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Stenosis >50% in “limus”-eluting DES
  • Symptoms/signs of ischemia
  • Number of enrollees: 402
  • Duration of follow-up: 1 and 3 years
  • Mean patient age: 68 years
  • Percentage female: 28%
  • Mean ejection fraction: 54%

Exclusions:

  • Acute STEMI
  • Cardiogenic shock
  • LMT lesion

Primary Endpoints:

  • Percent diameter stenosis at follow-up angiography at 6-8 months

Secondary Endpoints:

  • Death/MI at 1 year
  • Target lesion thrombosis at 1 year

Drug/Procedures Used:

Patients were randomized in a 1:1:1 fashion to either PTCA with a PEB (SeQuent Please, B Braun, Germany), repeat PCI with PES, or balloon PTCA alone. PEB catheters were coated with 3 μg of paclitaxel per mm2 of balloon surface with iopromide as hydrophilic spacer (length 10-30 mm; diameter 2.5-4.0 mm). All patients received an adenosine diphosphate (ADP) receptor antagonist prior to the procedure.

During the procedure, patients received intravenous aspirin and heparin with or without glycoprotein inhibitors or bivalirudin. If multiple restenotic lesions were present in a patient, the same strategy had to be pursued in that patient. All patients received 200 mg aspirin daily indefinitely and 6 months of ADP-receptor antagonist.

Principal Findings:

A total of 402 patients were randomized, 137 to PEB, 131 to PES, and 134 to balloon PTCA. Baseline characteristics were fairly similar between the three arms. About 42% had diabetes, and 94% had multivessel disease. Approximately 20% of patients presented with a non–ST-segment elevation myocardial infarction (NSTEMI). ISR was focal in about two-thirds of the patients, diffuse in 27%, and occlusive in 4%. The mean lesion length was 12.5 mm. The index DES was SES in 53% of patients, ZES in 15%, and EES in 28%. Cutting balloons were used in <1% of patients. Residual stenosis post-procedure was highest in the balloon PTCA arm (18.5% vs. 12.8% vs. 23.3% for PEB, PES, and balloon PTCA, respectively).

The primary endpoint of mean diameter (re)stenosis at 6-8 months of follow-up angiography was similar between the PEB and PES arms (38.0% vs. 37.4%, p for noninferiority = 0.007), and superior for both PEB and PES versus balloon PTCA (38.0% vs. 37.4% vs. 54.1%, p for superiority < 0.0001 for both). Binary restenosis (>50%) rates were 26.5% vs. 24.0% vs. 56.7%, p = 0.61 for PEB vs. PES, p < 0.0001 vs. balloon PTCA. Similarly, target lesion revascularization (TLR) rates were 22.1% vs. 13.5% vs. 43.5% (p = 0.09 for PEB vs. PES; p < 0.0001 vs. balloon PTCA). Clinical outcomes at 1 year including death/MI (4.4% vs. 6.9% vs. 6.8%, p > 0.05) and target lesion thrombosis (0.7% vs. 0.8% vs. 0%, p > 0.05) were similar between the three arms.

Three-year outcomes: TLR for PEB vs. PES vs. balloon angioplasty: 33.3% vs. 24.2% vs. 50.8% (p = 0.11 for PEB vs. PES; p < 0.001 for PEB vs. balloon angioplasty). Between 1 and 3 years: 14.5% vs. 12.4% vs. 13.4%, p = NS). Death and death/MI were lower for PEB compared with PES: 6% vs. 15.3% (p = 0.02) and 10.4% vs. 18.3%,(p = 0.08). Target lesion thrombosis was also lower (0.8% vs. 1.6%, p = 0.53).

Interpretation:

The results of the ISAR-DESIRE 3 trial indicate that angioplasty with a PEB is similar in efficacy to repeat PES PCI in patients presenting with DES ISR. Both these approaches are superior to balloon PTCA alone. It should be noted that the majority of these patients had focal ISR. These results make a strong case for considering PEB as the first-line therapy for DES ISR, especially for focal lesions.

Efficacy is maintained at 3 years of follow-up, with comparable TLR rates between PEB and PES, and better for both compared with balloon angioplasty. The difference was mostly in the first year; between years 1-3, TLR rates were similar.

Higher death rates with PES compared with PEB are hypothesis-generating and deserve further study. Future studies will also need to compare PEB to newer-generation DES for this indication, which have largely superseded PES in routine clinical practice.

References:

Kufner S, Cassese S, Valeskini M, et al. Long-Term Efficacy and Safety of Paclitaxel-Eluting Balloon for the Treatment of Drug-Eluting Stent Restenosis: 3-Year Results of a Randomized Controlled Trial. JACC Cardiovasc Interv 2015;8:877-84.

Byrne RA, Neumann FJ, Mehilli J, et al., on behalf of the ISAR-DESIRE 3 investigators. Paclitaxel-eluting balloons, paclitaxel-eluting stents, and balloon angioplasty in patients with restenosis after implantation of a drug-eluting stent (ISAR-DESIRE 3): a randomised, open-label trial. Lancet 2013;381:461-7.

Presented by Dr. Robert Byrne at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2012), Miami, FL, October 26, 2012.

Clinical Topics: Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Chronic Angina

Keywords: Myocardial Infarction, Follow-Up Studies, Coronary Restenosis, Drug-Eluting Stents, Heparin, Constriction, Pathologic, Angioplasty, Balloon, Coronary, Hirudins, Stents, Paclitaxel, Contrast Media, Iohexol, Thrombosis, Diabetes Mellitus


< Back to Listings