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

Oct 26, 2023
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC; Kim A. Eagle, MD, MACC
Trial Sponsor:
Deutsches Herzzentrum
Date Presented:
10/26/2023
Date Published:
10/26/2023
Date Updated:
10/26/2023
Original Posted Date:
04/10/2013
References

Contribution To Literature:

Highlighted text has been updated as of October 26, 2023.

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.

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.

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, 3, and 10 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).

Ten-year results: Primary composite outcome (cardiac death, target vessel myocardial infarction, target lesion thrombosis, or TLR) for PEB vs. PES vs. balloon angioplasty: 55.9% vs. 62.4% vs. 72.0% (p < 0.001). TLR: 43.9% vs. 38.6% vs. 58% (p < 0.0001). No difference was noted for PEB vs. PES for both of these outcomes. No difference in overall all-cause (28.6% vs. 38.7%, p = 0.15) and cardiac (28.6% vs. 32.6%, p = 0.40) death was noted for PEB vs. PES, but on landmark analysis, there was a higher risk of both with PES between 0-5 years and not between 5-10 years.

At the end of follow-up (10.3 years), first repeat TLR (R-TLR) was required in 204 lesions, 82 in the plain balloon (PB), 70 in the DCB, and 52 in DES group. Total number of R-TLR was 373: 162 in PB, 124 in DCB, and 87 in DES group. After 1 year, the risk of total R-TLR was nonsignificantly reduced by DCB (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.51-1.16) and significantly reduced by DES (HR 0.61 [0.39-0.95]) as compared with PB. Risk in the DCB vs. DES-group was similar (HR 1.26 [0.82-1.92]).

Interpretation:

The results of the ISAR-DESIRE 3 trial indicate that angioplasty with a paclitaxel-coated balloon 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 was 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.

At 10 years, there was no difference for the composite endpoint and TLR between PEB and PES, but there was a higher risk of mortality with PES between 0-5 years.

Higher death rates with PES compared with PEB are hypothesis-generating and deserve further study. Repeat TLR over 10 years was high for all modalities; DCB and DES did better than balloon PTCA for this purpose. Future studies will also need to compare PEB to newer-generation DES for this indication, which have superseded PES in routine clinical practice.

References:

Koch T, Lenz T, Rheude T, et al. Recurrent Revascularization at 10 Years After Percutaneous Treatment of Drug-Eluting Stent Restenosis. JACC Cardiovasc Interv 2023;Oct 26:[Epublished].

Editorial Comment: Waksman R, Chitturi KR. Myths and Truths in the Management of Drug-Eluting Stent In-Stent Restenosis. JACC Cardiovasc Interv 2023;Oct 26:[Epublished].

Presented by Dr. Tobias Koch at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2023), San Francisco, CA, October 26, 2023.

Giacoppo D, Alvarez-Covarrubias HA, Koch T, et al. Coronary artery restenosis treatment with plain balloon, drug-coated balloon, or drug-eluting stent: 10-year outcomes of the ISAR-DESIRE 3 trial. Eur Heart J 2023;44:1343-57.

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: Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease

Keywords: Percutaneous Coronary Intervention, TCT23, Transcatheter Cardiovascular Therapeutics


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