DIABETES: Diabetes and Sirolimus-Eluting Stent Trial

Luis Gruberg, MD, FACC

Disclosures

October 25, 2004

Editorial Collaboration

Medscape &

Presenter: Manel Sabaté, MD, Hospital Clinico San Carlos (Madrid, Spain)

Diabetic patients are known to suffer from a higher incidence of cardiovascular disease than persons without diabetes. Furthermore, these patients are known to be at an increased risk for restenosis after percutaneous coronary intervention (PCI) with and without stent placement. Restenosis rates after balloon angioplasty in diabetes patients can be very high (up to 63%), and although stenting has been shown to decrease these rates, these patients continue to have significantly higher restenosis rates and clinical events following PCI. Sirolimus-eluting stents (SES) are effective for the prevention of in-stent restenosis, and subgroup analyses of previous trials have shown a beneficial effect of these stents in diabetic patients.

Hypothesis: SES reduce the degree of neointimal hyperplasia after stenting in diabetic patients.

Aim: To assess the efficacy of the SES following successful stent implantation in diabetic patients with de novo coronary artery stenoses.

Study Design: DIABETES was a multicenter, prospective, randomized, placebo-controlled trial carried out in 4 centers in Spain. Subrandomization was also performed according to the type of diabetes. The trial was institutionally driven and was not commercially supported.

Primary Endpoint: In-segment (in-stent and edges) late lumen loss as assessed by quantitative coronary angiography (QCA) performed at 9-month angiographic follow-up

Secondary Endpoints:

  • Restenosis at follow-up

  • Minimal lumen diameter

  • In-stent and edges (in-segment) neointimal hyperplasia and percent of volume obstruction by intravascular ultrasound

  • Major adverse cardiac events (MACE; cardiac death, myocardial infarction, and target vessel revascularization)

  • Development of complications (aneurysm formation, late thrombosis, edge effect, late stent malapposition).

The study enrolled diabetic patients (insulin and non-insulin treated) with native coronary artery lesions and symptoms or evidence of ischemia. Those with in-stent restenosis, bifurcation lesions, recent myocardial infarction (< 72 hours), and chronic renal or hepatic failure were excluded from the study.

Results

A total of 160 patients were evenly randomized to SES or bare metal stent implantation. Both patient groups were well balanced with respect to age, the distribution of insulin- vs non-insulin-dependent diabetes, and left ventricular function. SES patients had a higher rate of prior coronary artery bypass graft surgery and a lower rate of multivessel disease than patients in the baremetal stent group, but the differences were not statistically significant (Table 1).

Table 1. DIABETES: Baseline Characteristics
Characteristic SES
(n = 80)
Bare Metal Stent
(n = 80)
Age (yrs) 66 67
Female (%) 27 27
Insulin-dependent diabetes (%) 33 34
Non-insulin-dependent diabetes(%) 67 66
Hypertension (%) 66 66
Hyperlipidemia (%) 61 61
Smoker (%) 45 50
S/P MI (%) 31 43
S/P CABG (%) 18 4
Multivessel disease (%) 61 69
Ejection fraction (%) 67 64
P = NS for all values
CABG = coronary artery bypass graft; MI = myocardial infarction; S/P = status-post

The number of lesions and their respective characteristics were also well balanced between the 2 patient groups (Table 2). More than half of all patients were treated with glycoprotein IIb/IIIa inhibitors, and all patients were treated with aspirin and clopidogrel for at least 1 year.

Table 2. DIABETES: Lesion Characteristics
Characteristic SES
(n = 111)
Bare Metal Stent
(n = 110)
Lesion length (mm) 14.5 ± 8.2 15.3 ± 7.6
Reference diameter (mm) 2.33 ± 0.5 2.35 ± 0.5
Class B2-C (%) 80 80
Total occlusion (%) 13 14
Left anterior descending (%) 39 44
Left circumflex (%) 23 24
Right coronary artery (%) 40 33
Multivessel stenting (%) 23 24
Lesions per patient (n) 1.4 ± 0.6 1.4 ± 0.5
Stents per patient (n) 1.6 ± 0.8 1.7 ± 0.9
P = NS for all values

At 1-month clinical follow-up, there were no significant differences between the 2 groups regarding death, myocardial infarction, or target lesion/vessel revascularization.

At 9-month follow-up, the use of an SES was associated with an 88% reduction in late lumen loss (primary endpoint) compared with patients in the bare metal stent group (Figure 1).

Figure 1. DIABETES: late lumen loss at 9-month follow-up (primary endpoint).

In-segment (Figure 2) and in-stent (Figure 3) restenosis rates were also significantly lower in SES patients. Late loss was not affected by type of diabetes (Figure 4).

Figure 2. DIABETES: in-segment restenosis.
Figure 3. DIABETES: in-stent restenosis.
Figure 4. DIABETES: late loss -- insulin- vs non-insulin-dependent diabetes.

Clinical follow-up at 9 months was similar between the 2 groups with respect to rates of cardiac death and myocardial infarction. Target lesion revascularization rates and MACE (cardiac death, myocardial infarction, and target vessel revascularization), however, were significantly lower in the SES arm (P < .0001; Figure 5). At the end of 9 months, the percentage of SES patients who remained free of MACE was significantly higher than that of control patients (88.7% vs 63.7%, respectively; P < .005).

Figure 5. DIABETES: 9-month clinical follow-up.
Conclusions
  1. The use of the SES effectively reduced in-segment late lumen loss and restenosis rates when compared with bare metal stents.

  2. This beneficial effect led to a significantly lower rate of the need for repeat revascularization procedures at 9-month clinical follow-up.

  3. There was no difference in the degree of reduction in restenosis parameters between insulin-dependent and non-insulin-dependent patients treated with the SES.

  4. The sirolimus-eluting stent appears to be safe in diabetic patients, and there were no cases of late stent thrombosis during the 9-month follow-up period while patients remained on clopidogrel therapy.

Comments

The results of this study showed that it is safe and feasible to treat diabetic patients with an SES. We have to remember that these patients are at a significantly higher risk for developing in-stent restenosis and therefore frequently undergo repeat revascularization procedures when treated with bare metal stents (as proved once again in the control arm of the present study). Late lumen loss was also very low in patients treated with the sirolimus-eluting stent, even in insulin-treated patients. Furthermore, single-digit restenosis rates in diabetic patients had never been seen, and these results, in a very well-designed study, certainly will have a huge impact on the way we treat diabetic patients with coronary artery disease. Larger patient trials will be needed to formally conclude the exact role of SES for the management of insulin-dependent diabetic patients.

Comments

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