Studies Support DES Use in Diabetics, But Results Vary by Device

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Two papers highlight the safety and effectiveness of drug-eluting stents (DES) in patients with diabetes who need revascularization, either on an elective or emergent basis. However, according to the results published online March 1, 2011, ahead of print in Circulation: Cardiovascular Interventions, it appears that the choice of DES may matter.

Zotarolimus Stent Fares Worse Than First-Generation DES

For the Naples-Diabetes (Novel Approaches for Preventing or Limiting Events in Diabetic Patients) trial, Carlo Briguori, MD, PhD, and colleagues at Clinica Mediterranea (Naples, Italy) looked at 422 consecutive patients with diabetes who underwent PCI of de novo lesions in native coronary arteries at their institution from October 2005 to January 2007. Subjects were randomized to receive sirolimus-eluting Cypher Select stents (n = 76; Cordis/Johnson & Johnson, Miami Lakes, FL), paclitaxel-eluting Taxus Liberté stents (n = 75; Boston Scientific, Natick, MA), or zotarolimus-eluting Endeavor Sprint stents (n = 75; Medtronic CardioVascular, Santa Rosa, CA).

At 3 years, the primary endpoint of MACE (all-cause death, MI, and clinically driven TLR or TVR) was highest in the Endeavor group at 35.6%, compared with 13.2% in the Cypher group and 17.5% in the Taxus group (P = 0.006). The discrepancy was mainly due to need for repeat revascularization. Post hoc comparisons showed no difference between Cypher and Taxus, but Endeavor had a higher MACE rate than either Cypher (P = 0.012) or Taxus (P = 0.075).

On multivariable analysis, independent predictors of 3-year MACE risk were:

• Treatment with Endeavor vs. Cypher stents (HR 2.35; 95% CI 1.07-5.41; P = 0.030)
• Multivessel disease (HR 1.78; 95% CI 1.06-2.66; P = 0.031)
• Diabetic retinopathy (HR 1.60; 95% CI 1.03-2.76; P = 0.038)
• Poor metabolic control (HR 1.60; 95% CI 1.02-2.52; P = 0.048)

In an e-mail communication with TCTMD, Dr. Briguori said he was surprised by the results. “At the time of the study design, the Endeavor Sprint was supposed to be as effective as the first- generation DES (Cypher, Taxus) in preventing restenosis, and also it was supposed to be safer, with lower risk for stent thrombosis,” he noted, adding that the majority of previous research comparing DES had follow-up limited to less than 1 year. “In particular, in diabetic patients it is clear that longer follow-up is mandatory to assess differences in performance of different DES. This study highlights this important concept.”

Asked what can be done to improve results in diabetic patients, he replied that the new Endeavor Resolute stent seems more effective at preventing restenosis than the Endeavor Spirit. “[Future] studies using the Endeavor Resolute will clarify whether this new DES is comparable to Cypher and Taxus in preventing restenosis in diabetic patients,” Dr. Briguori commented.

DES Lower TLR in STEMI Patients—Including Diabetics

A new analysis of the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial led by Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), meanwhile, focuses on the effect of diabetes on patients undergoing primary PCI for STEMI.

Subjects were randomly assigned to receive either paclitaxel-eluting Taxus Express² stents or otherwise identical BMS (both Boston Scientific). Though overall results were published in 2009, the trial’s design also stratified patients according to diabetes status at the time of randomization, such that each treatment arm contained a similar proportion of diabetic patients. In all, 478 patients with diabetes and 2,575 without diabetes were enrolled.

Overall, the 12-month composite rates of death, reinfarction, stroke, and ischemia-driven TVR were higher in diabetic than nondiabetic patients (14.8% vs. 10.3%; P = 0.003), a difference driven by significant increases in all-cause mortality (6.3% vs. 3.0%; P < 0.001) and stroke (2.0% vs. 0.8%; P = 0.02).

The use of Taxus vs. BMS was associated with reduced likelihood of ischemia-driven TLR at 1 year in both nondiabetic and diabetic patients, although the benefit in the latter group was mainly observed in insulin-treated subjects (table 1).

Table 1. Risk of Ischemia-Driven TLR: Taxus vs. BMS

 

One-year safety endpoints, including death, reinfarction, stroke, and stent thrombosis, were similar for Taxus and BMS in both the diabetic and nondiabetic cohorts. But within the diabetic group, Academic Research Consortium definite or probable stent thromboses were more common among those requiring insulin regardless of stent type (8.3% Taxus, 13.3% BMS) than among those who did not require insulin (1.2% Taxus, 1.2% BMS).

In terms of angiographic outcomes, at 13 months both in-stent and in-segment late loss and binary restenosis were significantly lower among diabetes patients who received Taxus compared with BMS.

The current report is valuable in that it “represents the largest, randomized controlled trial to date in diabetic patients with STEMI,” the paper notes.

Moreover, the observation that Taxus stents “can mitigate the increased restenosis risk imparted by diabetes” in STEMI patients bolsters previous studies backing the use of paclitaxel-eluting stents in patients without STEMI, Dr. Stone and colleagues add. “These results suggest that paclitaxel may act independent of signaling pathways affected by diabetes.” However, large, randomized trials are needed to assess whether angiographic and clinical outcomes with paclitaxel-eluting stents differ from those obtained by other DES, they note.

In an e-mail communication with TCTMD, Dr. Stone stressed that “[d]iabetic patients are a high-risk group with particularly poor outcomes after STEMI, even with successful primary PCI.” However, the improvement in event-free survival with paclitaxel-eluting stents was marked, especially in the highest risk group of patients with insulin-treated diabetes, he pointed out.

“The present study and others have largely refuted concerns about increased stent thrombosis with DES compared to BMS in STEMI. Further studies are required to determine if the benefits with rapamycin-analogue eluting stents in diabetic patients are similar, greater, or lesser,” Dr. Stone commented.

Note: Dr. Stone is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 

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Sources:
1. Briguori C, Airoldi F, Visconti G, et al. Novel approaches for preventing or limiting events in diabetic patients (Naples-Diabetes) trial: A randomized comparison of 3 drug-eluting stents in diabetic patients. Circ Cardiovasc Interv. 2011;Epub ahead of print.

2. Witzenbichler B, Wöhrle J, Guagliumi G, et al. Paclitaxel-eluting stents compared with bare metal stents in diabetic patients with acute myocardial infarction: The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Circ Cardiovasc Interv. 2011;Epub ahead of print.

 

 

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• Superiority of Everolimus Over Paclitaxel Stent Does Not Extend to Diabetics
• Diabetics with DES May Need Stronger, Longer Antiplatelet Therapy
• Use of DES vs. BMS Halves Restenosis in Diabetics with No Safety Signal