Gruppo Italiano di Studio sullo Stent nelle Occlusioni Coronariche—supported by GISE (Societa Italiana di Cardiologia Invasiva) - GISSOC II-GISE

Jul 13, 2010
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Grant from Cordis Italia, Sesto San Giovanni, Italy
Date Published:
01/01/2010
Date Updated:
07/13/2010
Original Posted Date:
07/13/2010
References

Description:

Although drug-eluting stents (DES) are frequently used following successful canalization of chronic total coronary occlusions (CTOs), randomized data to support this approach are scarce. Accordingly, the GISSOC II trial sought to compare outcomes after sirolimus-eluting stents (SES) versus bare-metal stent (BMS) implantation in patients with CTOs.

Hypothesis:

SES would be superior to BMS in patients with CTOs.

Study Design

  • Parallel
  • Randomized

Patient Populations:

  • Age >18 years 
  • De novo CTO of native coronary artery 
  • Reference vessel diameter: 2.75-3.75 mm 
  • Clinical presentation with angina, silent ischemia, myocardial viability
  • Number of screened applicants: 541
  • Number randomized: 152
  • Mean patient age: 63.9 years
  • Duration of follow-up: 8 months (angiographic), 24 months (clinical)
  • Percentage female: 17%
  • Ejection fraction: 55%
     

Exclusions:

  • MI within 30 days in the territory of the target CTO, or within 3 days in another territory 
  • Left ventricular ejection fraction <30%
  • Serum creatinine >3 mg/dl
  • Other comorbid conditions, with life expectancy <2 years
  • Contraindications to aspirin or clopidogrel
  • Women of child bearing potential
  • Left main disease
  • CTO involving a bifurcation, with a side branch >2 mm

Primary Endpoints:

  • In-segment minimal luminal diameter at 8 months

Secondary Endpoints:

  • In-segment late luminal loss at 8 months 
  • Restenosis at 8 months 
  • Major adverse cardiac events at 24 months 
  • Stent thrombosis at 24 months

Drug/Procedures Used:

Patients with angiographic evidence of CTO >30 days in a native coronary artery were randomized to receive either SES (Cypher, Cordis, Miami, FL) or BMS (Bx Sonic, Cordis).

Concomitant Medications:

A load of 300 mg of clopidogrel was given to patients who were not pretreated prior to the procedure. Post-procedure, all patients received aspirin 100-300 mg/day indefinitely, and clopidogrel for a minimum of 6 months.

Principal Findings:

Of the 541 patients who were screened, overall CTO success was 63.6%. A total of 152 patients were randomized, 74 to SES and 78 to BMS. Baseline characteristics were fairly similar between the two arms. The duration of the occlusion was short (1-3 months) in about 7%, and >3 months in 33%; this information was not available for about 60% of the patients. About 22% had diabetes mellitus, 56% had a history of smoking, 6% had prior coronary artery bypass grafting, and 17% had prior percutaneous coronary intervention. About 16% of patients had class III or IV angina, and 21% presented with unstable angina. Angiographically, about 34% had evidence of three-vessel disease, with the right coronary artery as the target vessel in about 47% of the patients. The majority of CTOs were crossed with hydrophilic wires (89%), with a mean of 1.6 stents per CTO, and a mean stented length of about 39 mm. The mean reference vessel diameter was 2.64 mm, with a mean occlusion length of 15.4 mm.

In-segment minimal luminal diameter at the end of the procedure was significantly lower in the SES arm, as compared with BMS (1.94 mm vs. 2.13 mm, p = 0.015). Despite this, the primary endpoint of in-segment minimal luminal diameter at 8 months was significantly higher in the SES arm (1.98 mm vs. 0.98 mm, p < 0.001). This corresponded to a lower mean % stenosis (31.0% vs. 66.4%, p < 0.001), and a lower late lumen loss (-0.10 mm vs. 1.10 mm, p < 0.001) in the SES arm, as compared with the BMS arm. Both in-stent (8.2% vs. 67.7%, p < 0.001) and in-segment (9.8% vs. 67.7%, p < 0.001) angiographic restenosis were also lower in the SES arm. Total reocclusions were also reduced with SES (0% vs. 16.9%, p = 0.001). Clinically, this translated into a significant reduction in the need for target lesion revascularization (TLR) with SES at 24 months (8.1% vs. 44.9%, p < 0.001). Other endpoints such as mortality (2.7% vs. 1.3%, p = 0.6), myocardial infarction (MI) (2.7% vs. 5.1%, p = 0.7), and stent thrombosis (1.4% vs. 1.3%, p = 1.0) were similar between the two arms. Fewer patients in the SES arm had evidence of angina or silent ischemia during follow-up (15.1% vs. 32.1%, p = 0.014).

Interpretation:

While the TOSCA trial demonstrated the superiority of BMS over PTCA for the treatment of CTOs, this was still associated with a high incidence of restenosis in the BMS arm. The PRISON II trial was one of the first trials to compare the use of DES (SES) to BMS in patients with CTOs, and noted a lower incidence of angiographic restenosis and TLR at 6 months with SES, as compared with BMS. Similar results were noted in the current GISSOC II-GISE trial at 8 months angiographically, and 24 months clinically. The ongoing PRISON III trial is designed to compare a zotarolimus-eluting stent (second generation DES) to SES (first generation DES) in patients with CTOs.

References:

Rubartelli P, Petronio AS, Guiducci V, et al. Comparison of sirolimus-eluting and bare metal stent for treatment of patients with total coronary occlusions: results of the GISSOC II-GISE multicentre randomized trial. Eur Heart J 2010;Jun 20:[Epub ahead of print].

Keywords: Myocardial Infarction, Coronary Restenosis, Drug-Eluting Stents, Sirolimus, Constriction, Pathologic, Angioplasty, Balloon, Coronary, Smoking, Metals, Thrombosis, Coronary Vessels, Coronary Occlusion, Coronary Artery Bypass, Diabetes Mellitus


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