Everolimus-Eluting Stent Compared to Paclitaxel-Eluting Stent
Everolimus-Eluting Stent Compared to Paclitaxel-Eluting Stent
Abstract & Commentary
By Andrew Boyle, MBBS, PhD Dr. Boyle is Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco Dr. Boyle reports no financial relationships relevant to this field of study.
Source: Stone GW, et al. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial. JAMA. 2008;299: 1903-1913.
Sirolimus and paclitaxel-eluting stents have been available for use in the United States since 2003 and have a well-known safety and efficacy profile. However, these drug and polymer combinations are applied to older generation stents, which are less deliverable than the newer generation stents. Recently, the zotarolimus-eluting stent was also released onto the US market. The present study describes another novel drug-eluting stent system. This system utilizes a novel anti-proliferative drug to prevent in-stent restenosis (ISR), everolimus, which is an analogue of sirolimus and inhibits smooth muscle cell proliferation after stent deployment. The drug coats a new generation, flexible, low profile, cobalt-chromium stent.
Stone and colleagues present the results of the SPIRIT III trial, comparing the clinical performance and safety of the everolimus-eluting stent (EES) to the well-known paclitaxel-eluting stent (PES). In this prospective, multi-center, single-blind, controlled trial, 1002 patients with de novo coronary artery lesions were randomized in a 2:1 ratio to receive everolimus-eluting (n = 669) or paclitaxel-eluting (n = 333) stents. Patients over 18 years of age were included if they had stable angina, unstable angina, or inducible ischemia. Following mandatory balloon predilation of the lesion, angiographic inclusion criteria (de novo lesions in native coronary arteries 2.5-3.75mm in diameter and < 28mm in length) were confirmed and telephone randomization was performed. There were multiple clinical exclusion criteria, including prior or planned percutaneous coronary intervention (PCI) in the target or non-target vessel, recent myocardial infarction (MI), prior or planned organ transplantation, prior brachytherapy, current or planned chemotherapy, immunologic or autoimmune disease, chronic anticoagulation, allergy to stent, polymer or drug components, planned elective surgery, elevated serum creatinine > 2.5mg/dL, dialysis, liver disease, stroke or TIA within 6 months, pregnancy, lactation, bleeding diathesis, or co-morbid conditions that limit life-expectancy. Angiographic exclusion criteria included bifurcation lesion with either side branch > 50% stenosed, excessive proximal tortuosity, lesion angulation or calcification, the presence of thrombus, lesion stenosis < 50% or 100%, and the presence of additional coronary artery lesions with stenoses > 40% that may require PCI during follow-up.
Each patient received full-dose aspirin and a loading dose of 300 mg clopidogrel either before or immediately after the procedure. Anti-thrombins used were either unfractionated heparin or bivalirudin at the operator's discretion; the use of glycoprotein IIb/IIIa inhibitors was also at the individual operator's discretion. Stent lengths were selected to cover approximately 3 mm of non-diseased vessel at either side of the lesion. Additional study stents were allowed for edge dissections or otherwise suboptimal results. Post-dilation was at the operator's discretion. A subset of patients completed angiographic follow-up at 8 months (n = 436); a subset of these had intravascular ultrasound follow-up as well. The cohorts were well matched in terms of baseline characteristics, other than a slight preponderance of unstable angina in the PES group.
The primary end point, in-segment late loss at 8-month follow-up angiography, was significantly lower in the EES group (0.14 ± 0.39 vs 0.26 ± 0.46; P = 0.003). There was no difference in the pre-specified secondary end point of target vessel failure; however, in the other pre-specified secondary end point, major adverse cardiac events (MACE) at one year were lower in the EES group vs the PES group (6.0 vs 10.3%; P = 0.02).
In-segment binary angiographic restenosis occurred in 4.7% of EES and 8.9% of PES group (P = 0.07). IVUS data at 8 months was available in 101 lesions treated with EES and 41 lesions treated with PES. Less neo-intima was seen in EES compared to PES-treated lesions (10.1 ± 11. vs 20.9 ± 31.5mm3; P = 0.04). There were no differences in immediate or late-acquired stent incomplete apposition. Importantly, there was no difference in stent thrombosis, either by protocol definition or by academic research consortium (ARC) definite, probable or possible definitions between groups. ARC definite or probable stent thrombosis occurred in 1.1% of EES and 0.6% of PES at one year; P = 0.73. Clinical outcomes at one year showed no difference in death, MI, target lesion failure, or target vessel failure. Stone et al conclude that the everolimus-eluting stent compared with the paclitaxel-eluting stent resulted in reduced angiographic late loss, non-inferior rates of target vessel failure, and fewer major adverse cardiac events during one-year follow-up.
Commentary
This study demonstrates that EES reduces ISR compared to PES, as assessed by angiographic late lumen loss and confirmed by IVUS volumetric analysis. This resulted in a trend toward less target lesions revascularization, but the study was not powered to assess this outcome. However, it should be noted that the exclusion criteria in this study were extensive and these results may not be the same in "real-world" situations where off-label use is high and more complex patients and lesions are treated than in this cohort. The resulting higher rates of ISR may result in different outcomes than seen in this study. However, the results are clearly demonstrated in this cohort and confirm the earlier SPIRIT II data. Furthermore, this is the first study showing superiority of one drug-eluting stent over another in terms of clinical events. Although this is a secondary end point and, therefore, requires further study in prospective, randomized trials addressing this as the primary outcome, this is a promising signal and reflects safety of this new stent system. Importantly, despite the low clopidogrel loading dose, the rates of stent thrombosis remained low in both groups.
A fourth drug-eluting stent system is welcome on the market as competition drives prices down and makes health-care more affordable. The everolimus-eluting stent system studied in SPIRIT III is not yet available in the United States; however, pending FDA approval, two companies plan to market the same stent system under different names at the same time. This would be the first such arrangement in US stent history and, as such, is noteworthy. What this means to healthcare companies and hospitals in terms of cost structures remains to be seen.
Sirolimus — and paclitaxel-eluting stents have been available for use in the United States since 2003 and have a well-known safety and efficacy profile. However, these drug and polymer combinations are applied to older generation stents, which are less deliverable than the newer generation stents.Subscribe Now for Access
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