Everolimus-eluting Stent Group Research Articles

Abstract 11911: Comparison of Late Catch-Up Phenomenon Between Sirolimus-Eluting Stent and Everolimus-Eluting Stent During 3 Years Follow-Up - a Propensity Matched Study -

Background: Recent studies have suggested the possibility of late catch-up phenomenon after implantation of sirolimus-eluting stent (SES) for coronary artery disease (CAD) compared to bare metal stent. However, little is known about the incidence of late catch-up phenomenon after implantation of everolimus-eluting stent (EES). Methods: Between April 2007 and May 2011, 1234 patients with CAD were treated with SES and 502 patients were treated with EES in our institution. We used a propensity score matching method with 1:1 matching, including 495 patients treated with SES and 495 patients treated with EES. Late catch-up phenomenon which was defined as target lesion restenosis (1 year to 3 years) were compared between the 2 groups. Results: After the propensity matching, no difference was seen in baseline characteristics between the 2 groups. Cumulative incidence of TLR at 3 years was 7.1% in EES group and 13.5% in SES group (P=0.001, log-rank test). Incidence of late catch-up phenomenon was 4.2% in EES group and 7.8% in SES group (P=0.020, log-rank test). Multivariate Cox’s proportional hazard analysis revealed that sirolimus eluting stent usage (HR 4.7, 95%CI 2.8-7.9, P<0.001), hemodialysis (HR 2.7, 95%CI 1.5-4.9, P=0.001), 2 stent use for bifurcation (HR 2.1, 95%CI 1.1-4.1, P=0.028), IVUS usage (HR 0.41, 95%CI 0.27-0.62, P<0.001), and ACS (HR 1.9, 95%CI 1.0-3.4, P=0.038) were independent predictors of late catch up phenomenon. Conclusions: EES was significantly superior to SES in the incidence of late catch-up phenomenon.

Abstract 13607: Differential Response of Local Coagulation after Implantation of New Generation Drug-Eluting Stents Compared with Sirolimus-Eluting Stent

Purpose: We have previously demonstrated local persistent hypercoagulation after sirolimus-eluting stent (SES) implantation by measuring plasma prothrombin fragment F1+2(frF1+2) levels. The aim of this study is to examine local coagulation response after biolimus-eluting stent (BES) and everolimus-eluting stent (EES) implantation. Methods: Sixty-eight patients who were treated with stents about eight months earlier to the mid-segment of the left anterior descending coronary artery, with no evidence of restenosis, were studied (BES: 12pts, EES: 15pts, SES: 23pts, and BMS: 18pts). We measured plasma levels of frF1+2 sampled in coronary sinus (CS) and sinus of Valsalva (V). The transcardiac frF1+2 gradients (ΔfrF1+2) were defined as CS level minus V level. The patients were divided into 2 groups according to total stent length [longer stent group (≥24mm) or shorter stent group (<24mm)]. Results: A larger percent diameter stenosis was observed in the BMS group than in the SES, EES, and BES groups (25.1±15.6 vs 7.1±16.5, 12.5±12.8, 10.3±14.2%, p<0.05, respectively). The ΔfrF1+2 was greater in the SES group than in the BMS, EES, and BES groups, and no significant differences were observed among the BMS, EES, and BES groups (23.4±21.1 vs 4.7±13.4, 3.2±11.7, 1.5±11.1 pmol/l, p<0.05, respectively). The ΔfrF1+2 in longer stent group (n=11) was significantly greater than in shorter stent group (n=12) (27.4±12.1 vs 19.2±10.1 pmol/l, p<0.05) only in the SES group, however, no significant differences were observed according to total stent length in other groups. Conclusions: A lower response of local coagulation after BES and EES implantation was shown, and significant correlation between local hypercoagulation and total stent length was observed only after SES implantation. These findings might be associated with lower strut thickness and unique characteristics of polymer in second-generation drug-eluting stents.

Abstract 12801: Angled Lesions Have Higher Incidence of Vascular Injury and Incomplete Stent Apposition, as Compared to Non-Angled Lesions, Following Stenting: An Optical Coherence Tomography Study

Backgrounds: Angled lesions are reported to be associated with worse procedural and clinical outcomes. Recent ex vivo studies have demonstrated that an angled arterial wall is exposed to imbalanced mechanical stress, which can cause vessel injuries and incomplete stent apposition (ISA) following stent implantation. Hypothesis: We tested the hypothesis that the angled coronary lesions, compared to non-angled lesions, would have higher incidence of vascular complications and ISA following stent implantation using optical coherence tomography (OCT) in patients. Methods: A total of 245 lesions treated with a single DES [95 zotarolimus-eluting stent (ZES) and 150 everolimus-eluting stent (EES)] were analyzed using OCT. An angled lesion was defined as a lesion on a curve ≥45° (n=59) on an angiogram and non-angled lesion on a curve <45° (n=186). The frequency was expressed as the percentage of stents with at least one type of injury or strut malapposition. Vessel injury included edge dissection, in-stent dissection, thrombus, and tissue protrusion. ISA was defined when the distance between the center of strut and the vessel wall was >100μm in ZES and >90um in EES. Results: The incidence of edge dissection and tissue protrusion was not significantly different between the groups. However, the incidence of in-stent dissection (84.7% vs 63.4%, P<0.01), thrombus (55.9% vs 35.5%, P<0.01) and ISA (76.3% vs 44.6%, P<0.001) was significantly higher in the angled group. The multivariate analysis demonstrated that the lesion on angle ≥60° was the independent predictor for in-stent dissection [Odds ratio (OR) 4.37, P=0.03] and ISA [OR 7.37, P<0.01], and that the angle ≥45° was the independent predictor for thrombus [OR 2.94, P=0.01]. There was no difference in the OCT findings between the ZES and EES groups. Conclusion: Angled coronary lesions had higher incidence of in-stent dissection, thrombus and ISA compared with non-angled lesions following DES implantation as assessed by OCT.

Long-term risk of late and very late stent thrombosis in patients treated with everolimus against paclitaxel-eluting stents: an updated meta-analysis.

Everolimus-eluting stent (EES) reduces the risk of late and very late stent thrombosis (ST) in a number of randomized controlled trials (RCTs). However, the benefits have been variable. We evaluated the effect of EES and paclitaxel-eluting stent (PES) on the risk of late and very late ST in patients with coronary artery disease. We identified RCTs by a systematic search of MEDLINE, EMBASE, and Cochrane Database. Seven RCTs (8162 patients) were included. Overall, EES therapy lowered the risk of very late ST significantly [relative risk (RR), 0.40; 95% confidence interval (CI), 0.20-0.80; I(2)=0.0%; P=0.009] compared with PES. Meanwhile, EES was associated with a significantly lower incidence of major adverse cardiac events (RR, 0.76; 95% CI, 0.67-0.86; I(2)=34.2%; P=0.00) driven by a markedly lower rate of myocardial infarction and target-vessel revascularization in the EES group. However, there was no significant difference in the risk of late ST (RR, 0.45; 95% CI, 0.15-1.39; I(2)=30.7%; P=0.166) between the two groups. A subgroup analysis showed that EES might not decrease the risk of very late ST significantly in patients older than 63.5 years or in patients with diabetes, those presenting with acute coronary syndrome, or those with a longer follow-up. Compared with PES, EES treatment decreased risk of very late ST significantly. However, the risk of late ST was similar between the two groups. More studies are needed to confirm the subgroup findings.

Optical coherence tomography study of healing characteristics of paclitaxel-eluting balloons vs. everolimus-eluting stents for in-stent restenosis: the SEDUCE (Safety and Efficacy of a Drug elUting balloon in Coronary artery rEstenosis) randomised clinical trial.

Little is known about the respective healing responses and clinical efficacy and safety of drug-eluting balloons (DEB) and the second generation of drug-eluting stents (DES) when used to treat in-stent restenosis (ISR). In this study, we set out to compare prospectively the healing characteristics, as assessed by optical coherence tomography (OCT), of DEB versus DES after treatment of ISR in bare metal stents (BMS). Fifty patients with BMS ISR were randomised to treatment with a paclitaxel-eluting balloon vs. an everolimus-eluting stent (EES). The primary endpoint was the percentage of uncovered struts, assessed with OCT at nine months, as a marker of vessel wall healing. A mean of 366±135 and 636±184 struts were analysed per patient in the DEB and EES groups, respectively. The percentage of uncovered struts per patient was significantly lower with DEB vs. EES (1.4% vs. 3.1%, p=0.025). Mean neointimal hyperplasia area was 2.4±1.08 mm in DEB vs. 1.92±0.67 mm in EES (p=0.1806), while the percentage of malapposed struts per patient was very low in both groups (0.2% vs. 0.3%, p=0.699). At nine months, angiographic in-stent MLD (minimum lumen diameter) was lower (2.13 vs. 2.54 mm, p=0.006), while diameter stenosis (26.4 vs. 11.4%, p=0.002), and LLL (0.28 vs. 0.07 mm, p=0.1) were higher after DEB compared to EES. During one-year follow-up, we did not observe differences in the rates of death, TLR (target lesion revascularisation) or stent thrombosis. DEB appears to be associated with better healing characteristics, as assessed by stent strut coverage with OCT, but tended to be slightly less effective compared to EES. These findings give support to the use of either DEB or EES as valuable treatment options for ISR. http://www.clinicaltrials.gov. Unique identifier: NCT 01065532.

Three-Year Outcomes After Revascularization With Everolimus- and Sirolimus-Eluting Stents From the SORT OUT IV Trial

ObjectivesThe study sought to compare the risk of late outcome with a focus on very late definite stent thrombosis of the everolimus-eluting stent (EES) with that of the sirolimus-eluting stent (SES) at 3-year follow-up. BackgroundIn the SORT OUT IV (SORT OUT IV Trial), comparing the EES with the SES in patients with coronary artery disease, the EES was noninferior to the SES at 9 months. The SORT OUT IV trial provides long-term head-to-head randomized comparison of the EES with the SES. MethodsWe prospectively randomized 2,774 patients in the SORT OUT IV trial. Follow-up through 3 years was complete in 2,771 patients (99.9%). The 3-year pre-specified endpoints were composites of safety and efficacy (major adverse cardiac events [MACE]: cardiac death, myocardial infarction, target vessel revascularization, and definite stent thrombosis). ResultsAt 3 years, the composite endpoint MACE occurred in 9.8% of the EES group and in 11.1% of the SES group (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.70 to 1.12). Overall rate of definite stent thrombosis was lower in the EES group (0.2% vs. 1.4%; HR: 0.15, 95% CI: 0.04 to 0.50), which was largely attributable to a lower risk of very late definite stent thrombosis: 0.1% versus 0.8% (HR: 0.09, 95% CI: 0.01 to 0.70). ConclusionsAt 3-year follow-up, the MACE rate did not differ significantly between EES- and SES-treated patients. A significant reduction of overall and very late definite stent thrombosis was found in the EES group. (The SORT OUT IV TRIAL [SORT OUT IV]; NCT00552877).

Two-year vessel healing after everolimus-eluting stent implantation: Serial assessment by optical coherence tomography

BackgroundPrevious reports have suggested the importance of delayed arterial healing and the development of neoatherosclerosis as major contributors to stent thrombosis and delayed restenosis. The difference of in vivo assessment of long-term vessel healing between first-generation drug-eluting stents and current generation everolimus-eluting stents (EESs) is limited. The aim of this study was to evaluate long-term arterial healing in EES in comparison with the first generation sirolimus-eluting stents (SES). MethodsWe evaluated 31 EES (23 patients) and 8 SES (7 patients) by serial optical coherence tomography at 12 months (mid-phase) and 24 months (late-phase) after stenting and evaluated the change in neointimal thickness (NIT), the percentages of uncovered struts, peri-strut low intensity area (PLIA; region around stent struts homogenously lower-intensity appearance than surrounding tissue), and thrombus. ResultsAlthough the average NIT showed no significant changes from the mid- to the late-phase follow-up in both EES and SES groups, the change in NIT and minimum lumen area was significantly larger in SES than EES (5.2±29.4 vs. 37.2±48.9; p=0.02, −0.06±0.36 vs. −0.45±0.74; p=0.04, respectively). The incidence of uncovered struts and struts with PLIA of EES was lower than those of SES, at both phases. Stents with in-stent thrombus of EES tended to be lower than that of SES at both phase follow-ups. ConclusionAlthough both SES and EES showed progressive luminal narrowing from the mid- to the late-phase follow-up, the extent of delayed lumen narrowing and delayed neointimal proliferation was significantly less in the second generation EES than the first generation SES. EESs seem to offer sustained stability in efficacy, without sacrificing safety, up to 2 years after implantation.

Long-Term Clinical Outcomes After Everolimus- and Sirolimus-Eluting Coronary Stent Implantation

Long-term clinical outcomes of everolimus-eluting stent (EES) compared with sirolimus-eluting stent (SES) have not been evaluated fully yet, especially whether EES implantation could positively affect late adverse events reported after SES implantation occurring >1 year. In this all-comer prospective multicenter randomized open-label trial, 3196 patients were assigned randomly to implant either EES (n=1596) or SES (n=1600). At 3 years, EES was noninferior to SES on the primary safety end point (all-cause death or myocardial infarction; 10.1% versus 11.5%; noninferiority P <0.001; and superiority P=0.19). Cumulative incidence of definite stent thrombosis was low and was not significantly different between the 2 groups (0.5% versus 0.6%; P=0.81). There was no significant difference in the efficacy end point of target-lesion revascularization between the EES and SES groups (6.6% versus 7.9%; P=0.16). However, the cumulative incidence of target-lesion failure (cardiac death/target-vessel myocardial infarction/ischemia-driven target-lesion revascularization) was significantly lower in the EES group than in the SES group (8.8% versus 11.4%; P=0.01). By a landmark analysis at 1 year, the cumulative incidence of very late stent thrombosis and late target-lesion revascularization was not significantly different between the 2 groups (0.2% versus 0.2%; P=0.99 and 2.2% versus 2.9%; P=0.21, respectively). The efficacy and safety outcomes for this trial after EES implantation remained comparable with those after SES implantation through 3-year follow-up. However, improvement of clinical outcome after EES implantation compared with SES implantation was suggested by the significantly lower cumulative incidences of target-lesion failure, which has been the most widely used primary end point in the stent-versus-stent trials. http://www.clinicaltrials.gov. Unique identifier: NCT01035450.

Seguimiento de 3 años de pacientes con lesiones de bifurcación tratados con stents liberadores de sirolimus o everolimus: estudio de colaboración de SEAside y CORpal

Introduction and objectivesTo compare the 3-year incidence of major events in patients with bifurcation lesions treated with provisional sirolimus-eluting stents vs everolimus-eluting stents. MethodsA pooled analysis of 2 prospective randomized trials with similar methodology (SEAside and CORpal) was performed. In these trials, 443 patients with bifurcation lesions were randomly assigned to treatment with either sirolimus-eluting stents or everolimus-eluting stents. The clinical follow-up was extended up to 3 years to assess major adverse cardiovascular events (death or acute myocardial infarction or target vessel revascularization). ResultsAt 3 years, survival free of major adverse cardiovascular events was 93.2% vs 91.3% in the everolimus-eluting stent group vs the sirolimus-eluting stent group (P = .16). Exploratory land-mark analysis for late events (occurring after 12 months) showed significantly fewer major adverse cardiovascular events in the everolimus-eluting stent group: 1.4% vs 5.4% in the sirolimus-eluting stent group (P = .02). ConclusionsProvisional stenting with either sirolimus-eluting stents or everolimus-eluting stents in bifurcation lesions is associated with low rates of major adverse events at 3-years’ follow-up. The results of a subanalysis of events beyond 1 year, showing a lower event rate with everolimus-eluting stents than with sirolimus-eluting stents, suggest that studies exploring the long-term clinical benefit of the latest generation of drug-eluting stents are warranted.Full English text available from: www.revespcardiol.org/en

Three-year Follow-up of Patients With Bifurcation Lesions Treated With Sirolimus- or Everolimus-eluting Stents: SEAside and CORpal Cooperative Study

Introduction and objectivesTo compare the 3-year incidence of major events in patients with bifurcation lesions treated with provisional sirolimus-eluting stents vs everolimus-eluting stents. MethodsA pooled analysis of 2 prospective randomized trials with similar methodology (SEAside and CORpal) was performed. In these trials, 443 patients with bifurcation lesions were randomly assigned to treatment with either sirolimus-eluting stents or everolimus-eluting stents. The clinical follow-up was extended up to 3 years to assess major adverse cardiovascular events (death or acute myocardial infarction or target vessel revascularization). ResultsAt 3 years, survival free of major adverse cardiovascular events was 93.2% vs 91.3% in the everolimus-eluting stent group vs the sirolimus-eluting stent group (P = .16). Exploratory land-mark analysis for late events (occurring after 12 months) showed significantly fewer major adverse cardiovascular events in the everolimus-eluting stent group: 1.4% vs 5.4% in the sirolimus-eluting stent group (P = .02). ConclusionsProvisional stenting with either sirolimus-eluting stents or everolimus-eluting stents in bifurcation lesions is associated with low rates of major adverse events at 3-years’ follow-up. The results of a subanalysis of events beyond 1 year, showing a lower event rate with everolimus-eluting stents than with sirolimus-eluting stents, suggest that studies exploring the long-term clinical benefit of the latest generation of drug-eluting stents are warranted.

The EXAMINATION Trial (Everolimus-Eluting Stents Versus Bare-Metal Stents in ST-Segment Elevation Myocardial Infarction): 2-Year Results From a Multicenter Randomized Controlled Trial

This study sought to assess the 2-year outcomes of the population included in the EXAMINATION (Everolimus-Eluting Stents Versus Bare-Metal Stents in ST-Segment Elevation Myocardial Infarction) trial beyond the 1-year prescription period of dual antiplatelet therapy. The EXAMINATION trial compared the performance of everolimus-eluting stents (EES) versus bare-metal stents (BMS) in an all-comer ST-segment elevation myocardial infarction (STEMI) population. This was a multicenter, multinational, prospective, randomized, single-blind, controlled trial in patients with STEMI. The primary endpoint, which was the combined endpoint of all-cause death, any recurrent myocardial infarction, and any revascularization, and the endpoints target lesion revascularization and stent thrombosis were assessed at 2 years. Between December 31, 2008, and May 15, 2010, 1,498 patients were randomized to receive EES (n = 751) or BMS (n = 747). Compliance with dual antiplatelet regimen was reduced at 2 years to a similar degree (17.3% vs. 17.2%, p = 0.91). At 2 years, the primary endpoint occurred in 108 (14.4%) patients of the EES group and in 129 (17.3%) patients of the BMS group (p = 0.11). Rate of target lesion revascularization was significantly lower in the EES group than in the BMS group (2.9% vs. 5.6%; p = 0.009). Rates of definite and definite or probable stent thrombosis were also significantly reduced in the EES group (0.8% vs. 2.1%; p = 0.03, and 1.3% vs. 2.8%; p = 0.04, respectively). The 2-year follow-up of the EXAMINATION trial confirms the safety and efficacy of the EES compared with BMS in the setting of STEMI. Specifically, both rates of target lesion revascularization and stent thrombosis were reduced in recipients of EES without any signs of late attrition for either of these endpoints. (A Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST-Segment Elevation Myocardial Infarction: EXAMINATION Study; NCT00828087).

Two-Year Outcomes After First- or Second-Generation Drug-Eluting or Bare-Metal Stent Implantation in All-Comer Patients Undergoing Percutaneous Coronary Intervention: A Pre-Specified Analysis From the PRODIGY Study (PROlonging Dual Antiplatelet Treatment After Grading stent-induced Intimal hyperplasia studY)

This study sought to assess device-specific outcomes after implantation of bare-metal stents (BMS), zotarolimus-eluting Endeavor Sprint stents (ZES-S), paclitaxel-eluting stents (PES), or everolimus-eluting stents (EES) (Medtronic Cardiovascular, Santa Rosa, California) in all-comer patients undergoing percutaneous coronary intervention. Few studies have directly compared second-generation drug-eluting stents with each other or with BMS. We randomized 2,013 patients to BMS, ZES-S, PES, or EES implantation. At 30 days, each stent group received up to 6 or 24 months of clopidogrel therapy. The key efficacy endpoint was the 2-year major adverse cardiac event (MACE) including any death, myocardial infarction, or target vessel revascularization, whereas the cumulative rate of definite or probable stent thrombosis (ST) was the key safety endpoint. Clinical follow-up at 2 years was complete for 99.7% of patients. The MACE rate was lowest in EES (19.2%; 95% confidence interval [CI]: 16.0 to 22.8), highest in BMS (32.1%; 95% CI: 28.1 to 36.3), and intermediate in PES (26.2%; 95% CI: 22.5 to 30.2) and ZES-S (27.8%; 95% CI: 24.1 to 31.9) groups (chi-square test = 18.9, p = 0.00029). The 2-year incidence of ST in the EES group (1%; 95% CI: 0.4 to 2.2) was similar to that in the ZES-S group (1.4%; 95% CI: 0.7 to 2.8), whereas it was lower compared with the PES (4.6%, 95% CI: 3.1 to 6.8) and BMS (3.6%; 95% CI: 2.4 to 5.6) groups (chi-square = 16.9; p = 0.0001). Our study shows that cumulative MACE rate, encompassing both safety and efficacy endpoints, was lowest for EES, highest for BMS, and intermediate for PES and ZES-S groups. EES outperformed BMS also with respect to the safety endpoints with regard to definite or probable and definite, probable, or possible ST. (PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY [PRODIGY]; NCT00611286).

Clinical outcomes of everolimus- and zotarolimus-eluting stents in patients with acute myocardial infarction for small coronary artery disease

Background and purposeThere were limited data about comparison of zotarolimus-eluting stents (ZES) and everolimus-eluting stents (EES) in patients with small coronary artery disease (CAD), especially in patients with acute myocardial infarction (AMI). The objective of this study was to compare the clinical outcomes of ZES and EES in patients with AMI for small CAD. Methods and subjectsA total 1565 AMI patients treated with Endeavor-ZES (n=651) (Medtronic CardioVascular, Santa Rosa, CA, USA) or Xience V/Promus-EES (n=914) (Abbott Vascular, Temecula, CA/Boston Scientific, Natick, MA, USA) for small CAD (stent diameter ≤2.75mm) in KAMIR (Korea Acute Myocardial Infarction Registry) were enrolled. After propensity score matching to adjust for baseline clinical and angiographic characteristics, we compared a total 1302 patients (651 ZES and 651 EES) about major adverse cardiac events (MACE) at 1-year. Subgroup analysis about 1-year clinical outcomes was undertaken in patients who were discharged alive. ResultsBaseline clinical and angiographic characteristics were similar between the two groups after propensity score matching. Total MACE did not differ between the two groups before (9.8% vs. 8.2%, p=0.265) and after (9.8% vs. 9.4%, p=0.778) propensity score matching. The EES group showed lower rate of 1-year cardiac death (5.4% vs. 3.3%, p=0.041), target lesion failure (TLF; 6.9% vs. 4.3%, p=0.022), and stent thrombosis (1.4% vs. 0.4%, p=0.042) compared with the ZES group. However, there were no differences in 1-year cardiac death, TLF, and stent thrombosis in propensity score matched populations. Other various 1-year clinical outcomes showed no difference between the two groups. Subgroup analysis in patients who were discharged alive showed similar outcomes between the two groups at 1-year follow-up. ConclusionIn-this propensity score matched analysis, EES and ZES showed no significant difference in clinical outcomes at 1-year follow-up in patients with AMI for small CAD.

Third-Generation ZES Matches EES in Efficacy and Safety, without Evidence of Longitudinal Deformation in an All-Comer Population

This article presents 1-year data from the Durable Polymer-Based Stent Challenge of Promus Element Versus Resolute Integrity in an All Comers Population [DUTCH PEERS (TWENTE II); von Birgelen C et al. Lancet 2013 (epublished ahead of print)] study. The results demonstrated comparable clinical outcomes with zotarolimus-eluting stents and everolimus-eluting stents (EES); both are third-generation, permanent, polymer-based, drug-eluting stents. There was no significant difference in efficacy and safety between the two stents, and longitudinal stent deformation was only seen in the EES group.

Third-generation zotarolimus-eluting and everolimus-eluting stents in all-comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single-blind, multicentre, non-inferiority trial

Third-generation, permanent-polymer-based drug-eluting stents with novel, flexible designs might be more easily delivered than previous generations of stents in complex coronary lesions, but might be less longitudinally stable. We aimed to assess the safety and efficacy in all-comer patients of two third-generation stents that are often used clinically, but that have not yet been compared, and one of which has not previously been assessed in a randomised trial. In this investigator-initiated, single-blind, multicentre, randomised, two-arm, non-inferiority trial, patients aged 18 years and older who required a percutaneous coronary intervention with implantation of a drug-eluting stent were recruited from four study sites in the Netherlands. We randomly assigned patients by independently managed computer-generated allocation sequences in a 1:1 ratio to receive either cobalt-chromium-based zotarolimus-eluting stents (Resolute Integrity, Medtronic, Santa Rosa, CA, USA) or platinum-chromium-based everolimus-eluting stents (Promus Element, Boston Scientific, Natick, MA, USA). Patients and analysts were masked to the allocated stent, but treating clinicians were not. The primary endpoint of target-vessel failure was a composite of safety (cardiac death or target-vessel-related myocardial infarction) and efficacy (target-vessel revascularisation) at 12 months, analysed by intention to treat (with a non-inferiority margin of 3·6%). This trial is registered with ClinicalTrials.gov, number NCT01331707. Between Nov 25, 2010, and May 24, 2012, 1811 eligible all-comer patients, with 2371 target lesions, were enrolled in the study. 370 (20%) patients presented with ST-elevation myocardial infarction and 447 (25%) with non-ST-elevation myocardial infarction. 906 patients were assigned to receive zotarolimus-eluting stents and 905 to receive everolimus-eluting stents. Ease of stent delivery was shown by very low numbers of patients requiring treatment other than their assigned study treatment (six [1%] in the zotarolimus-eluting stent group vs five [1%] in the everolimus-eluting stent group; p=0·22). 12-month follow-up results were available for 1810 patients (one patient in the zotarolimus-eluting stent group withdrew consent). The primary endpoint was met by 55 (6%) of 905 patients in the zotarolimus-eluting stent group and 47 (5%) of 905 in the everolimus-eluting stent group. The zotarolimus-eluting stent was non-inferior to the everolimus-eluting stent (absolute risk difference 0·88%, 95% CI -1·24% to 3·01%; upper limit of one-sided 95% CI 2·69%; non-inferiority p=0·006). We noted no significant between-group differences in individual components of the primary endpoint. Definite stent thrombosis occurred in three (0·3%) patients in the zotarolimus-eluting stent group and six (0·7%) patients in the everolimus-eluting stent group (p=0·34). Longitudinal stent deformation was seen only in the everolimus-eluting stent group (nine [1·0%] of 905 vs 0 of 906, p=0·002; nine of 1591 [0·6%] everolimus-eluting stents implanted became deformed), but was not associated with any adverse events. Both stents were similarly efficacious and safe, and provided excellent clinical outcomes, especially in view of the large number of patients who presented with acute myocardial infarctions. Boston Scientific, Medtronic.

A Clinical and Angiographic Study of the XIENCE V Everolimus-Eluting Coronary Stent System in the Treatment of Patients With Multivessel Coronary Artery Disease: The EXECUTIVE Trial (EXecutive RCT: Evaluating XIENCE V in a Multi Vessel Disease)

This study sought to investigate the efficacy and performance of the XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Santa Clara, California) in the treatment of de novo coronary lesions in patients with 2- to 3-vessel multivessel coronary artery disease (MV-CAD). Drug-eluting stents (DES) have emerged as an alternative to conventional coronary artery bypass surgery in patients with MV-CAD although first-generation DES yielded inferior efficacy and safety compared with surgery. Prospective, randomized (1:1), multicenter feasibility trial was designed to assess angiographic efficacy of EES compared with the TAXUS paclitaxel-eluting stent (PES) in 200 patients, and a prospective, open-label, single-arm, controlled registry was designed to analyze the clinical outcome of EES at 1-year follow-up in 400 MV-CAD patients. For the randomized trial, the primary endpoint was in-stent late loss at 9 months. For the registry, the primary endpoint was a composite of all-cause death, myocardial infarction, and ischemia-driven target vessel revascularization at 12 months. The primary endpoint per single lesion was significantly lower in the EES group compared with the PES group (-0.03 ± 0.49 mm vs. 0.23 ± 0.51 mm, p = 0.001). Similar results were observed when analyzing all lesions (0.05 ± 0.51 mm vs. 0.24 ± 0.50 mm, p < 0.001). Clinical outcome at 1 year yielded a composite of major adverse cardiac events of 9.2% in the single-arm registry, and 11.1% and 16.5% in the EES and PES randomized groups, respectively (p = 0.30). The EXECUTIVE trial was a randomized pilot trial dedicated to the comparison of the efficacy of 2 different DES among patients with 2- to 3-vessel MV-CAD. The study shows lower in-stent late loss at 9 months with the EES XIENCE V compared with the PES TAXUS Libertè, and a low major adverse cardiac event rate at 1 year in patients with 2-to 3-vessel MV-CAD. (EXECUTIVE [EXecutive RCT: Evaluating XIENCE V in a Multi Vessel Disease]; NCT00531011).

Stent-oriented versus patient-oriented outcome in patients undergoing early percutaneous coronary intervention for acute coronary syndrome: 2-year report from the BASE-ACS trial

Background. The BASE-ACS trial demonstrated an outcome of the titanium-nitride-oxide-coated bioactive stents (BAS) statistically non-inferior to that of the everolimus-eluting stents (EES) at 12-month follow-up in patients presenting with acute coronary syndrome (ACS). We performed a post hoc analysis of the BASE-ACS trial with particular focus on stent-oriented versus patient-oriented outcome at 24-month follow-up.Methods. A total of 827 patients with ACS were randomly assigned to receive either BAS (417) or EES (410). Stent-oriented outcome was defined as a composite of cardiac death, target vessel-related non-fatal myocardial infarction, or ischemia-driven target lesion revascularization. Patient-oriented outcome was defined as a composite of all-cause death, any non-fatal myocardial infarction, or any revascularization.Results. Clinical follow-up for 24 months was completed in 406 (97.4%) patients in the BAS group and in 398 (97.1%) in the EES group. Stent-oriented outcome at 24-month follow-up occurred at similar frequencies in the two stent groups (10.1% for BAS versus 11.2% for EES, P = 0.53). Likewise, patient-oriented outcome at 24-month follow-up was similar in the two groups (16.3% versus 19.8%, respectively, P = 0.2).Conclusions. In patients presenting with ACS, the rates of both stent-oriented and patient-oriented outcomes at 24-month follow-up in the BAS group were similar to those in the EES group.Trial registration: ClinicalTrials.gov identifier: NCT00819923.

Neointimal coverage and vasodilator response to titanium-nitride-oxide-coated bioactive stents and everolimus-eluting stents in patients with acute coronary syndrome: insights from the BASE-ACS trial

Incomplete stent endothelialization is associated with late and very late stent thrombosis. In a post hoc analysis of the BASE-ACS trial, we sought to assess neointimal coverage and coronary flow reserve (CFR) 9 months after implantation of titanium-nitride-oxide-coated bioactive stents (BAS) versus everolimus-eluting stents (EES) in patients with acute coronary syndrome (ACS). In the BASE-ACS trial, 827 patients with ACS were randomized to receive either BAS or EES. In the current study, we examined neointimal growth and strut coverage by optical coherence tomography and CFR by trans-thoracic echocardiography in 28 consecutive non-diabetic patients with the culprit lesion in the left anterior descending coronary artery. The primary endpoints were binary stent strut coverage and CFR at 9-month follow-up. A total of 13 patients were included in the BAS group (2,033 struts); 15 in the EES group (2,898 struts). Binary stent strut coverage was higher and malapposed struts lower with BAS versus EES (99.4 vs 89.2, and 0.2 vs 4.6%, respectively, p < 0.001 for both). Neointimal hyperplasia thickness was greater with BAS versus EES (274.2 vs 100.1 μm, respectively, p < 0.001). CFR was lower with EES versus BAS (2.2 ± 0.8 vs. 3.0 ± 0.5, respectively, p = 0.001). Abnormal CFR (<2.5) were detected in 10 patients in the EES group versus one in the BAS group (p = 0.002). The current study demonstrated that in patients with ACS, BAS resulted in improved neointimal stent strut coverage and better coronary vasodilator function as compared with EES at 9-month follow-up.

Zotarolimus- Versus Everolimus-Eluting Stents for Unprotected Left Main Coronary Artery Disease

This study sought to compare the safety and efficacy of the zotarolimus-eluting stent (ZES) and the everolimus-eluting stent (EES) for treatment of unprotected left main coronary artery (uLMCA) disease. The second-generation ZES and EES have reduced the risk of restenosis in large patient cohorts. However, their comparative performance in uLMCA lesions is not known. In this study, patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention for uLMCA lesions were randomly assigned to receive either a ZES (n = 324) or an EES (n = 326). The primary endpoint was the combined incidence of death, myocardial infarction, and target lesion revascularization at 1 year. Secondary endpoints were definite or probable stent thrombosis at 1 year and angiographic restenosis based on analysis of the left main coronary artery area at follow-up angiography. At 1 year, the cumulative incidence of the primary endpoint was 17.5% in the ZES group and 14.3% in the EES group (relative risk: 1.26; 95% confidence interval [CI]: 0.85 to 1.85; p = 0.25). Three patients in the ZES group (0.9%) and 2 patients in the EES group (0.6%) experienced definite or probable stent thrombosis (p > 0.99). All-cause mortality at 1 year was equal in the 2 groups (5.6%; relative risk: 1.00; 95% CI: 0.52 to 1.93; p = 0.98). Angiographic restenosis occurred in 21.5% of patients in the ZES group and 16.8% in the EES group (relative risk: 1.28; 95% CI: 0.86 to 1.92; p = 0.24). Within the statistical limitations of the present study, treatment of uLMCA lesions with a ZES or an EES provided comparable clinical and angiographic outcomes at 1-year follow-up.

Differential responses of local coagulation after implantation of everolimus-eluting and zotarolimus-eluting stents compared with early-generation drug-eluting stents in patients with stable angina

Purpose: We have previously demonstrated local persistent hypercoagulability after sirolimus-eluting stent (SES) implantation by measuring plasma prothrombin fragment F1+2 (frF1+2) levels. The aim of this study is to examine local coagulation response after everolimus-eluting stent (EES) and zotarolimus-eluting stent (ZES) implantation compared with early-generation drug-eluting [SES and paclitaxel-eluting stent (PES)] and bare metal stents (BMS). Methods: Eighty-five patients who were treated about eight months earlier with stents to the mid-segment of the left anterior descending coronary artery, with no evidence of restenosis, were studied (EES:12, ZES:15, PES:18, SES:20, and BMS:20). We measured plasma levels of frF1+2 sampled in coronary sinus (CS) and sinus of Valsalva (V). The transcardiac frF1+2 gradients (ΔfrF1+2) were defined as CS level minus V level. Results: A larger percent diameter stenosis (%DS) was observed in the ZES and BMS groups than in the SES (17.1±13.2, 25.1±15.6 vs 7.1±16.5%, p<0.05, respectively). There were no significant differences in %DS among SES, PES, and EES groups (7.1±16.5, 10.5±15.2, 12.6±12.9%, NS). There were no significant differences in ΔfrF1+2 among BMS, ZES, and EES groups (4.7±13.4, 5.5±8.4, 3.3±11.7 pmol/l, NS). The ΔfrF1+2 was smaller in the ZES and EES group, and larger in the PES group than in the SES group (5.5±8.4, 3.3±11.7, 32.3±24.2 vs 23.4±21.1 pmol/l, p<0.05, respectively). The ΔfrF1+2 significantly correlated with the total stent length in the SES group (r=0.53, p<0.05), however, it did not correlate in the EES, ZES, and PES groups. Conclusions: A decreased response of local coagulation after ZES and EES implantation and an increased one after PES implantation were observed, as compared to SES implantation. These findings might be associated with lower strut thickness, unique characteristics of polymer, and lower cytotoxic effect of eluted drug in second-generation drug-eluting stents.