Comparison of everolimus-eluting and paclitaxel-eluting coronary stents in patients with two treated vessels: 2-year results from the SPIRIT III randomised trial.

AIMS: To examine the two year clinical outcomes in dual-vessel disease from the SPIRIT III trial comparing the XIENCE V(r) everolimus-eluting stent (EES) to the TAXUS Express2(tm) paclitaxel-eluting stent (PES). METHODS AND RESULTS: From a total of 1,002 randomised subjects, 103 and 51 patients in the EES and PES groups respectively underwent stenting of two lesions in two vessels (one lesion per epicardial vessel). Two-year event rates were lower in one compared to two-vessel treated patients regardless of stent type. For EES vs. PES, major adverse cardiac events (MACE=cardiac death, MI or TLR) was clinically reduced 35.0% in the single vessel patients (6.5% vs. 9.6%, p=0.09) and was significantly reduced 64% in dual vessel patients (11.9% vs. 30.1%, p=0.006). There was no significant interaction between stent type (EES vs. PES) and the number of stented vessels (two vs. single) for either 2-year TVF and MACE (interaction p values were 0.69 and 0.16, respectively). CONCLUSIONS: In the SPIRIT III randomised trial, patients with both single and dual vessel treatment with EES showed improved clinical outcomes at two years compared to those treated with PES. Follow-up to five years is ongoing.

Recent progress in percutaneous coronary intervention: evolution of the drug-eluting stents, focus on the XIENCE V drug-eluting stent.

Although originally the practice of using balloon catheters proved successful in the short term, the long-term prognosis was less promising because of restenosis, which occurred in >or=30% of patients. This prompted the development of new techniques and mechanical adjuncts, or stents, to maintain lumen patency after balloon angioplasty. Bare metal stents (BMS), the first type of stent used in percutaneous coronary intervention, were designed to address the issues met by balloon angioplasty. BMS reduced the angiographic and clinical restenosis rates in de novo lesions compared to percutaneous transluminal coronary angioplasty alone and decreased the need for emergency coronary artery bypass graft surgery. BMS substantially reduced the incidence of abrupt artery closure, but restenosis still occurred after 6 months in about 20% of cases, necessitating repeat procedures. Drug-eluting stents (DES) improved on the principle of BMS by also delivering drugs locally to inhibit neointimal hyperplasia. DES greatly reduced the incidence of restenosis and resulted in a better safety profile as compared to radiation or systemic drug administration. These advantages and a lower cost compared to surgical interventions make DES an attractive option to treat coronary artery disease. Currently, five DES are available in the USA: the CYPHER sirolimus-eluting stent from Cordis (approved by FDA on 24 April 2003), the TAXUS Express(2) and Liberté paclitaxel-eluting stents from Boston Scientific (approved by FDA on 4 March 2004 and 10 October 2008, respectively) (hereafter TAXUS Express is referred to as TAXUS), the ENDEAVOR zotarolimus-eluting stent from Medtronic (approved by FDA on 1 February 2008), and the XIENCE V everolimus-eluting stent from Abbott Vascular (approved by FDA on 2 July 2008). Following the approval of CYPHER and TAXUS, the clinical data suggested a potential small increase in the rate of stent thrombosis (ST) in DES compared with BMS after implantation. To determine the differences in ST and other rare events between different stents, some modifications have been made to DES clinical trial design, and postmarket surveillance programs have been included to further evaluate the safety and efficacy of each DES. In this review, we will discuss the key clinical outcomes of DES clinical trials, design and key features of the current coronary stents, and major clinical development programs. Postmarket trials, designed to establish long-term safety around ST and other rare clinical events, are also discussed. The future of DES design technologies will also be outlined.

Pharmacokinetic sub-study in the SPIRIT III Randomized and Controlled Trial of XIENCE V everolimus eluting coronary stent system.

BACKGROUND: Drug-eluting stents (DES) are widely used for treatment of coronary artery disease with benefit of reduced restenosis compared to bare metal stents. The XIENCE VEverolimus Eluting Coronary Stent System is a second-generation DES system for better deliverability while maintaining safety and efficacy profiles. The present pharmacokinetic sub-study from the SPIRIT III Randomized and Controlled Trial (RCT) was to evaluate systemic exposure of patients to everolimus and to further demonstrate safety following implantation of XIENCE Vstents with everolimus doses ranging from 53 to 181 microg. METHODS AND RESULTS: Drug concentrations in whole blood were determined at multiple time points using a validated analytical method with a limit of quantification of 0.1 ng/mL. Individual C(max) ranged from 0.17 to 2.40 ng/mL and occurred between 0.07 and 1.88 hours across all dose levels. Both mean and individual C(max) values were below the trough blood concentrations of everolimus (Certican) for inhibition of organ transplant rejection. The last time point at which drug concentrations could be quantified ranged from 12 to 168 hours postimplantation in individual patients. In most cases, the blood levels dropped below the limit of quantification after 72 hours. CONCLUSIONS: This study confirms that the XIENCE Vstent causes a limited and systemic exposure to everolimus. The presumed localized and efficient delivery of everolimus to target vessels coupled with limited and transient systemic drug exposure contributes to the safety and effectiveness of the XIENCE VEECSS in patients of SPIRIT III RCT for longer than 2 years.

Clinical and angiographic comparison of everolimus-eluting and paclitaxel-eluting stents in small coronary arteries: a post hoc analysis of the SPIRIT III randomized trial.

BACKGROUND: Drug-eluting stents with low late loss may be particularly beneficial in small coronary arteries. We therefore examined whether the everolimus-eluting stent is superior to the paclitaxel-eluting stent in patients treated with 2.5-mm stents in the SPIRIT III trial. METHODS: The SPIRIT III trial was a prospective, multicenter, randomized (2:1; XIENCE V: TAXUS Express) trial in which 1002 patients were enrolled. One or more 2.5-mm stents were implanted in 160 patients in the XIENCE V arm, and 59 patients, in the TAXUS arm. Mean vessel diameter was 2.36 +/- 0.30 and 2.34 +/- 0.33 mm in the XIENCE V and TAXUS groups, respectively (P = .69). RESULTS: At 9 months, XIENCE V compared to TAXUS reduced the rates of major adverse cardiac events (cardiac death, myocardial infarction, or ischemic target lesion revascularization) from 12.5% to 3.2% (P = .02) and target vessel failure (cardiac death, reinfarction, or ischemic target vessel revascularization) from 16.1% to 5.2% (P = .02), the differences being driven primarily by reductions in target lesion revascularization (12.5% vs 1.3%; P = .002). In-stent late loss was significantly reduced by XIENCE V when compared to TAXUS (0.54 +/- 0.74 vs 0.11 +/- 0.43 mm, P = .01), as was In-segment binary angiographic restenosis (20.8% vs 4.1%, P = .02). CONCLUSIONS: In this post hoc analysis from the SPIRIT III trial, the XIENCE V 2.5-mm stent significantly reduced clinical and angiographic restenosis compared to the TAXUS 2.5-mm stent, further supporting the hypothesis that lower late loss is beneficial in small vessel disease.

Preprocedural inflammation does not affect neointimal hyperplasia following everolimus-eluting stent implantation.

BACKGROUND: Preprocedual C-reactive protein (CRP) has been reported to correlate with in-stent restenosis following bare-metal stent implantation. The aim of this study was to investigate the impact of preprocedural inflammation on neointimal hyperplasia assessed by intravascular ultrasound (IVUS) following everolimus-eluting stent (EES) implantation. METHODS: We identified 134 patients meeting the following criteria: 1) patients treated with EES; 2) those with stable or unstable angina; and 3) patients available for high-sensitivity (hs)-CRP before the procedure and volumetric IVUS analysis at follow up. We divided the patients into two groups on the basis of hs-CRP levels (< 3 or > or = 3 mg/L) before the procedure and compared IVUS parameters. Volume index (volume/length) was calculated for vessel (VVI), plaque (PVI), neointima (NIV), stent (SVI), and lumen (LVI). Percent neointimal volume (%NIV) was calculated as (NIV/SVI) x 100. Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%). RESULTS: There was no significant difference in VVI, PVI, or LVI at either baseline or 8-month follow up between the two groups. At 8-month follow up, there was also no significant difference in %NIV (4.93 +/- 5.66% vs. 4.98 +/- 5.25% p = 0.959) and maximum %CSN (16.81 +/- 13.62% vs. 18.14 +/- 13.91%; p = 0.608) as well as VVI, PVI, and LVI between the two groups. Furthermore, hs-CRP did not correlate with %NIV (r = 0.044; p = 0.610) and maximum %CSN (r = 0.086, p = 0.321) at follow up. There was no significant difference in incidence of late-acquired incomplete stent apposition between the two groups (1.2% vs. 0%; p = 0.512). CONCLUSION: Our results suggest that preprocedural inflammation does not affect neointimal hyperplasia following EES implantation.