Sirolimus-Eluting Superior to Paclitaxel-Eluting Stents in Patients with Diabetes

Sirolimus-Eluting Superior to Paclitaxel-Eluting Stents in Patients with Diabetes

By Laura Brasseur

The introduction of drug-eluting stents (DES) has significantly reduced the risk of restenosis, which is common with bare-metal stents. Two recent studies have conducted head-to-head comparisons between the 2 available DES to assess if there are differences in their safeties or efficacies. Results show that sirolimus-eluting stents is superior to paclitaxel-eluting stents in reducing the number of restenosis in high-risk patients, including patients with diabetes, as well as lowering the risk of major adverse cardiac events.

The first study compared the drug-eluting stents (DES) in 1012 patients with either stable angina or acute coronary syndromes (ACS) who required percutaneous coronary intervention (PCI) (N EnglJ Med.2005;353:653-662). Approximately 20% of the participants also had diabetes.

At 9-months’ follow-up, “as compared with polymer-based, paclitaxel-eluting stents, sirolimus-eluting stents resulted in fewer major adverse cardiac events at 9 months, primarily by decreasing the rates of clinical and angiographic stenosis [Table 1],” wrote Stephan Windecker, MD, Department of Cardiology, University Hospital Bern, Bern, Switzerland, and colleagues. “The difference was driven by a 44% reduction in the relative risk of target-lesion revascularization in favor of the sirolimus stent,” they wrote.

Angiographic measurements in 540 of the patients showed that 6.6% of the sirolimus group and 11.7% of the paclitaxel group had in-segment binary restenosis.

The second study, published in the same issue of the New England Journal of Medicine (pages 663-670), is the first to compare the 2 DES in high-risk patients with diabetes mellitus. The 250 participants also had coronary artery disease, a major contributor to death in patients with diabetes. Such patients are often treated with bypass surgery rather than with PCI for revascularization, because of their high risk of restenosis after PCI.

As in the first study, the sirolimus-eluting stent came out on top (Table 2). Patients treated with the paclitaxel stent were about twice as likely to have in-segment restenosis on follow-up (16.5% vs 6.9%; P = .03) and to require target-lesion revascularization (12.0% vs 6.4%; P = .13).

“Pharmacologic differences between the 2 drugs, differences in the dose response of patients with diabetes, or differences in the properties of the 2 drug-delivery stents…may account for the results,” according to Alban Dibra, MD, Deutsches Herzzentrum, Munich, Germany, and colleagues.

In an accompanying editorial (pages 724-727), David J. Moliterno, MD, Gill Heart Institute and Division of Cardiovascular Medicine, Where?, suggested other possible explanations for the results, including the fact that both trials were incomplete, with almost half of the patients in the first study and 18% in the second study not undergoing angiographic follow-up.

The choice of the most appropriate stent for an individual patient can depend on the risk of restenosis, “which is believed to be driven by several key factors, though most important of these, generally speaking, is vessel caliber or diameter,” Dr Moliterno told IMWR. “For large vessels (>3.5 mm), the risk of restenosis is reasonably low, and for this cohort, a bare-metal stent can be considered.” (For more about bare-metal stents vs DES, see page xx.)

He said that DES are indicated for vessels of intermediate-range diameter (ie, 2.5 to 3.5 mm) or if other factors are present, such as diabetes; current restenosis at the target site; renal insufficiency; and complex lesion morphology, including bifurcation stenoses, ostial location, and lesion irregularity.

“In head-to-head comparisons of these 2 DES, their risk for restenosis appears similar for lower-risk patients,” Dr Moliterno told IMWR. “The sirolimus-eluting stent has demonstrated an edge over the paclitaxel-eluting stent for patients at increased risk for restenosis, particularly those with diabetes or who are being treated for a presently existing restenosis [ie, who have previously received a stent to the target lesion].” He noted, however, that the paclitaxel-eluting stent may still be preferable because of “device availability, deliverability to the target lesion, and cost.”

Table 1. Comparison of DES in patients with stable angina/ACS,at 9 months

Outcome Sirolimus stent Paclitaxel stent P

N (%) N (%)

CV death 3 (0.6) 8 (1.6) .15

MI 14 (2.8) 18 (3.5) .49

Target-lesion revascularization 24 (4.8) 42 (8.3) .03

Target-vessel revascularization 30 (6.0) 47 (9.2) .05

Primary end point* 31 (6.2) 55 (10.8) .009

Target-vessel failure 35 (7.0) 59 (11.6) .01

*The primary end point was a composite of death from cardiac causes, MI, and ischemia-driven target-lesion revascularization.

DES = drug-eluting stents; ACS = acute coronary syndrome; CV = cardiovascular; MI = myocardial infarction.

Table 2. DES in diabetic patients with CAD: angiographic findings at 6.5 months (median)

Finding Paclitaxel stent Sirolimus stent P

Late luminal loss (mm)

In segment 0.67 0.43 .002

In stent 0.46 0.19 <.001

Stenosis (% of luminal diameter)

In segment 31.73 25.74 .02

In stent 24.22 16.59 .006

Angiographic restenosis (n [%])

In segment 17 (16.5) 7 (6.9) .03

In stent 14 (13.6) 5 (4.9) .03

DES = drug-eluting stents; CAD = coronary artery disease.