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.
Drugs/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 (200mg daily) and clopidogrel (300mg loading dose, 75mg daily for at least 6 months) at least 1 day prior to the procedure. Patients in the triple group received 200mg of cilostazol as a loading dose immediately after the procedure, followed by 100mg 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 >200mg/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.
Conditions
Diabetes mellitus
Coronary heart disease
Therapies
Stent/drug-eluting
Study Design
Randomized. Blinded. Parallel. Factorial.
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%
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
Patient Population
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/mm
Platelet count <100,000/mm
Alanine aminotransferase or aspartate aminotransferase ≥3x upper limit of normal
Serum creatinine ≥2.0mg/dl
Life expectancy <1 year secondary to noncardiac disease
Planned bifurcation stenting
Primary PCI for acute MI within 24 hours
Inability to follow protocol