A Randomized Comparison of Sirolimus- Versus Paclitaxel-Eluting Stent Implantation in Patients With Diabetes Mellitus - DES-DIABETES

Aug 18, 2008
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Trial Sponsor:
Cardiovascular Research Foundation (Korea), a grant from the Korean Ministry of Health & Welfare as part of the Korea Health 21 Research and Development Project
Date Published:
01/01/2008
Date Updated:
08/18/2008
Original Posted Date:
08/18/2008
References

Description:

Patients with diabetes mellitus and coronary artery disease (CAD) have been shown to have better outcomes with drug-eluting stents (DES) compared with bare-metal stents (BMS). This trial was aimed at performing a head-to-head comparison between sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) in diabetic patients with CAD.

Hypothesis:

SES would be associated with a lower incidence of in-stent restenosis compared with PES at 6 months of follow-up.

Study Design

Study Design:

Patients Screened: 423
Patients Enrolled: 400
Mean Follow Up: 6 months (angiographic), 9 months (clinical)
Mean Patient Age: 60.9 years
Female: 42
Mean Ejection Fraction: 59%

Patient Populations:

  • Patients with diabetes mellitus
  • Angina pectoris or positive stress test
  • Significant angiographic stenosis in a native coronary vessel with diameter stenosis ≥50%
  • Reference vessel diameter ≥2.5 mm

Exclusions:

  • Contraindication to cilostazol, aspirin, or clopidogrel
  • Left main disease
  • Graft vessel disease
  • Ejection fraction <30%
  • White blood cell count <3000/mm2
  • Platelet count <100,000/mm2
  • Alanine aminotransferase or aspartate aminotransferase ≥3x upper limit of normal
  • Serum creatinine ≥2.0 mg/dl
  • Life expectancy <1 year secondary to noncardiac disease
  • Planned bifurcation stenting
  • Primary PCI for acute MI within 24 hours
  • Inability to follow protocol

Primary Endpoints:

In-segment restenosis of at least 50% at 6 months

Secondary Endpoints:

  • In-segment late loss at 6 months
  • In-stent restenosis at 6 months
  • TVR
  • Stent thrombosis
  • MACE, including death, MI, and TLR

Drug/Procedures Used:

Once the guidewire had been advanced across the lesion, patients were randomized to either SES or PES in a 1:1 fashion.

Concomitant Medications:

In a 2 x 2 factorial design, patients received either triple drug therapy with cilostazol, clopidogrel, and aspirin, or dual drug therapy with clopidogrel and aspirin alone. All patients received aspirin (200 mg daily) and clopidogrel (300 mg loading dose, 75 mg daily for at least 6 months) at least 1 day prior to the procedure. Patients in the triple group received 200 mg of cilostazol as a loading dose immediately after the procedure, followed by 100 mg twice daily for 6 months. Glycoprotein IIb/IIIa inhibitors were used in 4.5% of the patients.

Principal Findings:

A total of 400 patients were randomized, 200 to SES and 200 to PES. The angiographic success rate was 99.5%. Baseline characteristics were similar between the two groups. The mean hemoglobin A1c was 7.8%, and about 16.3% of patients were insulin-dependent. About 30% of patients in both arms had a total cholesterol >200 mg/dl. Multivessel disease was noted in 64% of the patients. There was no difference between the two groups in terms of the total stented lengths or the number of implanted stents/lesion.

Follow-up angiography was performed in 82.5% of the patients. In-segment restenosis was noted less frequently with SES compared with PES (4.0% vs. 20.8%, relative risk 0.19, hazard ratio 0.09-0.42, p < 0.001), as was in-stent restenosis (3.4% vs. 18.2%, p < 0.001). The in-stent and in-segment late loss were both significantly lower in the SES group compared with the PES group.

At 9 months, there was no difference between the two groups in the incidence of death (0% vs. 0.5%) or myocardial infarction (MI) (0.5% vs. 0.5%). One episode of acute stent thrombosis was noted in the SES group, but none was noted in the PES group. The rates of target lesion revascularization (TLR) (2.0% vs. 7.5%, p = 0.017) and target vessel revascularization (TVR) (3.5% vs. 8.0%, p = 0.053) were significantly lower in the SES group compared with the PES group. Clinically driven TLR and TVR were both significantly lower in the SES group as well. The incidence of MACE was significantly lower in the SES group as well (2.0% vs. 8.0%, p = 0.01).

Interpretation:

The superiority of DES over BMS has been well established in patients with diabetes and CAD by various studies. The results of DES-DIABETES, one of the few head-to-head trials between the two most commonly used DES, indicate that SES may be associated with a lower incidence of in-segment and in-stent restenosis, along with a lower incidence of TLR, TVR, and major adverse cardiac events (MACE), but not mortality, MI, or stent thrombosis, in diabetic patients with CAD compared with PES.

These results are similar to the SIRTAX and ISAR-DIABETES trials, which also documented a lower rate of restenosis with SES in diabetic patients compared with PES. Further studies into long-term differences between the two DES in diabetic patients, including in rates of stent thrombosis, are necessary.

References:

Lee SW, Park SW, Kim YH, et al. A randomized comparison of sirolimus- versus paclitaxel-eluting stent implantation in patients with diabetes mellitus. J Am Coll Cardiol 2008;52:727-33.

Keywords: Risk, Coronary Artery Disease, Myocardial Infarction, Insulin, Follow-Up Studies, Drug-Eluting Stents, Sirolimus, Constriction, Pathologic, Stents, Paclitaxel, Cholesterol, Hemoglobins, Metals, Thrombosis, Diabetes Mellitus, Exercise Test


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