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.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Boston Scientific, Medtronic.

Three-year clinical outcome of patients with bifurcation treatment with second-generation Resolute and Xience V stents in the randomized TWENTE trial.

BACKGROUND: Only limited data from large randomized clinical trials have been published on the long-term performance of second-generation drug-eluting stents in bifurcation lesions. METHODS: We investigated in patients in the randomized TWENTE trial the long-term safety and efficacy of treating bifurcation lesions with 2 widely applied second-generation drug-eluting stents, the zotarolimus-eluting Resolute stent (Medtronic Inc, Santa Rosa, CA) and the everolimus-eluting Xience V stent (Abbott Vascular, Santa Clara, CA). Three-year follow-up was available in 99.3%. Patients were categorized into treatment for ≥1 bifurcation lesion versus treatment for nonbifurcation lesions only. RESULTS: Among the 1,391 patients of the TWENTE trial, 362 (26%) were treated for bifurcation lesions. At 3-year follow-up, target-vessel failure did not differ between patients treated for bifurcation versus nonbifurcation lesions (13.1% vs 12.6%; P = .84), whereas the periprocedural myocardial infarction rate was higher in patients with bifurcation lesions (6.9% vs 3.1%; P < .01). Of the 362 patients with bifurcation lesion treatment, 179 (49.4%) were treated with Resolute and 183 (50.6%) with Xience V. There was no significant difference in target-vessel failure between the Resolute and Xience V groups with bifurcation treatment (13.6% vs 12.6%; P = .78), and their incidence of definite-or-probable stent thrombosis was low and similar (1.1% vs 0.5%, respectively; P = .62). CONCLUSION: Despite a significant difference in periprocedural myocardial infarction, 3-year clinical outcome after implantation of second-generation stents was favorable and similar for patients with and without bifurcation lesions. In addition, we observed no difference in long-term clinical outcome after bifurcation lesion treatment with Resolute and Xience V stents.

Clinical outcome of patients with implantation of second-generation drug-eluting stents in the right coronary ostium: insights from 2-year follow-up of the TWENTE trial.

OBJECTIVES: The aim of the present study was to assess the impact on clinical outcome of right coronary artery (RCA) ostial coverage with second-generation drug-eluting stents (DES). BACKGROUND: Treatment of the aorta-ostial (AO) region of the RCA with bare metal stents and first-generation DES has been associated with a higher risk of target-lesion revascularization (TLR). METHODS: Of the 1,391 patients of the prospective TWENTE trial, we identified 321 (23%) with single-vessel RCA treatment, who were categorized into stenting with AO stent coverage (AOC) versus stenting without AOC. The AO region was defined as 3 mm from the aortic orifice. RESULTS: The 67 (20.9%) patients with AOC showed more severe lesion calcifications than the 254 patients without AOC (31.3% vs. 12.6%; P < 0.01). In the AOC group, there was a higher prevalence of hypercholesterolemia and family history of coronary disease (75.4% vs. 61.6%, and 68.7% vs. 53.5%, respectively; P = 0.03). During 2-year follow-up, patients in the AOC group had a higher incidence of TLR (7.5% vs. 1.6%; P = 0.02). Following adjustment for confounders, AOC independently predicted TLR with an adjusted hazard ratio of 4.1 (95% CI: 1.17-14.39; P = 0.03). CONCLUSION: AO treatment of the RCA with second-generation DES is feasible, but our data suggest that stent coverage of the right AO segment remains a predictor of TLR.

Three-year clinical outcome after treatment of chronic total occlusions with second-generation drug-eluting stents in the TWENTE trial.

OBJECTIVE: To compare long-term outcome of patients treated for chronic total occlusion (CTO) lesions versus patients treated for non-CTO lesions only. BACKGROUND: Percutaneous coronary interventions (PCI) for CTO lesions generally have a higher adverse event risk than PCI for non-CTO lesions. However, long-term outcome data from prospective studies with second-generation drug-eluting stent (DES) use in CTO lesions is scarce. METHODS: We analyzed in this substudy of the TWENTE trial the data of 674 patients, who had stable angina and were electively treated with second-generation DES (Resolute zotarolimus-eluting or Xience V everolimus-eluting stents). Main outcome parameter was target lesion failure (TLF), a composite of cardiac death, target vessel-related myocardial infarction (MI), or target lesion revascularization (TLR). RESULTS: Patients with CTO lesions (n = 59, 8.8%) were more often treated for lesions in small vessels (94.9% vs. 63.1%, P < 0.001), long lesions (52.5% vs. 17.7%, P < 0.001) and multiple vessels (42.4% vs. 22.4%, P < 0.001), and were less often males (62.7% vs. 74.6%, P < 0.05) than patients with non-CTO lesions (n = 615, 91.2%). J-CTO scores ≥2 were present in 56% of CTO lesions. Despite significant differences in characteristics of patients, lesions, and interventional procedures, the TLF rate at 3-year follow-up was similar for both groups (13.6% vs. 12.9%, P = 0.89). In addition, a patient-oriented composite endpoint (any death, MI or revascularization) did not differ between groups (18.6% vs. 18.8%, P = 0.97). CONCLUSION: Patients treated with second-generation DES for CTO lesions showed at 3-year follow-up an incidence of adverse clinical events that was low and similar to patients with non-CTO lesions only.

Complex patients treated with zotarolimus-eluting resolute and everolimus-eluting Xience V stents in the randomized TWENTE trial: comparison of 2-year clinical outcome.

OBJECTIVE: To assess the differences in clinical outcome between complex patients treated with Resolute zotarolimus-eluting stents (ZES) versus Xience V everolimus-eluting stents (EES). BACKGROUND: Nowadays, many complex patients with coronary disease are treated with percutaneous coronary interventions, using drug-eluting stents (DES). METHODS: We analyzed 2-year outcome data of 1,033 complex patients of the TWENTE trial, treated with second-generation Resolute ZES or Xience V EES. Complex patients had at least one of the following characteristics: renal insufficiency (creatinine ≥ 140 µmol/l); ejection fraction < 30%; acute myocardial infarction (MI) within previous 72 hrs; >1 lesion/vessel; >2 vessels treated; lesion length > 27 mm; bifurcation; saphenous vein graft lesion; arterial bypass graft lesion; in-stent restenosis; unprotected left main lesion; lesion with thrombus; or lesion with total occlusion. Target vessel failure (TVF), the primary composite endpoint of the trial, was defined as cardiac death, target vessel-related MI, or target vessel revascularization. RESULTS: Among the 1,033 complex patients, 529 (51%) were treated with Resolute ZES and 504 (49%) with Xience V EES. Patient- and procedure-related characteristics were similar between DES groups. After 2-year follow-up, outcome was also similar between DES groups. TVF occurred in 12.1% of patients treated with Resolute ZES and 12.3% of patients treated with Xience V EES. In addition, DES groups did not differ significantly in cardiac death, MI, or target vessel revascularization-the individual components of TVF. CONCLUSION: Complex patients treated with Resolute ZES and Xience V EES showed similar safety and efficacy during 2-year follow-up. © 2014 Wiley Periodicals, Inc.

Comparison of 3 biodegradable polymer and durable polymer-based drug-eluting stents in all-comers (BIO-RESORT): rationale and study design of the randomized TWENTE III multicenter trial.

AIM: To evaluate the safety and efficacy of 2 novel drug-eluting stents (DES) with biodegradable polymer-based coatings versus a durable coating DES. METHODS AND RESULTS: BIO-RESORT is an investigator-initiated, prospective, patient-blinded, randomized multicenter trial in 3540 Dutch all-comers with various clinical syndromes, requiring percutaneous coronary interventions (PCI) with DES implantation. Randomization (stratified for diabetes mellitus) is being performed in a 1:1:1 ratio between ORSIRO sirolimus-eluting stent with circumferential biodegradable coating, SYNERGY everolimus-eluting stent with abluminal biodegradable coating, and RESOLUTE INTEGRITY zotarolimus-eluting stent with durable coating. The primary endpoint is the incidence of the composite endpoint target vessel failure at 1 year, consisting of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Power calculation assumes a target vessel failure rate of 8.5% with a 3.5% non-inferiority margin, giving the study a power of 85% (α level .025 adjusted for multiple testing). The impact of diabetes mellitus on post-PCI outcome will be evaluated. The first patient was enrolled on December 21, 2012. CONCLUSIONS: BIO-RESORT is a large, prospective, randomized, multicenter trial with three arms, comparing two DES with biodegradable coatings versus a reference DES with a durable coating in 3540 all-comers. The trial will provide novel insights into the clinical outcome of modern DES and will address the impact of known and so far undetected diabetes mellitus on post-PCI outcome.

Contemporary guideline-directed medical therapy in de novo, chronic, and worsening heart failure patients: First data from the TITRATE-HF study.

AIMS: Despite clear guideline recommendations for initiating four drug classes in all patients with heart failure (HF) with reduced ejection fraction (HFrEF) and the availability of rapid titration schemes, information on real-world implementation lags behind. Closely following the 2021 ESC HF guidelines and 2023 focused update, the TITRATE-HF study started to prospectively investigate the use, sequencing, and titration of guideline-directed medical therapy (GDMT) in HF patients, including the identification of implementation barriers. METHODS AND RESULTS: TITRATE-HF is an ongoing long-term HF registry conducted in the Netherlands. Overall, 4288 patients from 48 hospitals were included. Among these patients, 1732 presented with de novo, 2240 with chronic, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and median ejection fraction was 35% (IQR 25-40). In total, 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of HFrEF patients achieved target dose for all drug classes. In addition, quadruple therapy was more often prescribed to patients treated in a dedicated HF outpatient clinic as compared to a general cardiology outpatient clinic. In each GDMT drug class, 19% to 36% of non-use in HFrEF patients was related to side-effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients already used one or more GDMT drug classes for other indications than HF. CONCLUSION: This first analysis of the TITRATE-HF study reports relatively high use of GDMT in a contemporary HF cohort, while still showing room for improvement regarding quadruple therapy. Importantly, the use and dose of GDMT were suboptimal, with the reasons often remaining unclear. This underscores the urgency for further optimization of GDMT and implementation strategies within HF management.

Women treated with second-generation zotarolimus-eluting resolute stents and everolimus-eluting xience V stents: insights from the gender-stratified, randomized, controlled TWENTE trial.

BACKGROUND: Women are underrepresented in clinical research, and few data are available from randomized head-to-head comparisons of second-generation drug-eluting stents (DES) in female patients. Aim of this study was to assess safety and efficacy of two second-generation DES in women. In TWENTE-a prospective, randomized, comparative DES trial-"real-world" patients were stratified for gender before randomization for Resolute or Xience V stents. METHODS: Target vessel failure (TVF; cardiac death, target vessel-related myocardial infarction, and clinically indicated target vessel revascularization) after 1 year was the predefined endpoint. RESULTS: Among 1,391 patients, 382 (27.5%) women were randomized to Resolute (n = 192) and Xience V (n = 190). Baseline and procedural characteristics were similar for females in both study arms, except for smaller vessel and stent diameters in Resolute-treated lesions. After 1 year, TVF (8.9 vs. 8.4%; adjusted odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.41-2.20, P = 0.91) and a patient-oriented composite endpoint (13.0 vs. 12.1%, P = 0.79) did not differ significantly between women in both arms. Women were older than men (P < 0.01) and had more often diabetes mellitus (26.4 vs. 19.8%, P = 0.01) and hypertension (63.6 vs. 52.5%, P < 0.01), but there was no significant gender difference in TVF (adjusted OR: 1.18, 95% CI: 0.73-1.92, P = 0.50). CONCLUSIONS: This gender-stratified TWENTE trial analysis resulted in no significant difference in safety and efficacy outcomes between Resolute- and Xience V-treated females.

DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity (DUTCH PEERS): rationale and study design of a randomized multicenter trial in a Dutch all-comers population.

BACKGROUND: Drug-eluting stents (DES) are increasingly used for the treatment of coronary artery disease. An optimized DES performance is desirable to successfully treat various challenging coronary lesions in a broad population of patients. In response to this demand, third-generation DES with an improved deliverability were developed. Promus Element (Boston Scientific, Natick, MA) and Resolute Integrity (Medtronic Vascular, Santa Rosa, CA) are 2 novel third-generation DES for which limited clinical data are available. Accordingly, we designed the current multicenter study to investigate in an all-comers population whether the clinical outcome is similar after stenting with Promus Element versus Resolute Integrity. METHODS: DUTCH PEERS is a multicenter, prospective, single-blinded, randomized trial in a Dutch all-comers population. Patients with all clinical syndromes who require percutaneous coronary interventions with DES implantation are eligible. In these patients, the type of DES implanted will be randomized in a 1:1 ratio between Resolute Integrity versus Promus Element. The trial is powered based on a noninferiority hypothesis. For each stent arm, 894 patients will be enrolled, resulting in a total study population of 1,788 patients. The primary end point is the incidence of target vessel failure at 1-year follow-up. SUMMARY: DUTCH PEERS is the first randomized multicenter trial with a head-to-head comparison of Promus Element and Resolute Integrity to investigate the safety and efficacy of these third-generation DES.

Scanning electron microscopic assessment of coating irregularities and their precursors in unexpanded durable polymer-based drug-eluting stents.

OBJECTIVES: To assess and quantify coating irregularities on unexpanded and expanded durable polymer-based drug-eluting stents (DES) to gain insights into the origin of coating irregularities. BACKGROUND: Previous scanning electron microscopy (SEM) studies in various expanded DES revealed differences in frequency and size of coating irregularities between DES types and specific distribution patterns, however, the origin of these irregularities is unclear. METHODS: We assessed at bench side a total of 1,200 SEM images obtained in 30 DES samples (15 expanded and 15 unexpanded) of Cypher Select Plus, Taxus Liberté, Endeavor, Xience V, and resolute. RESULTS: For most coating irregularities seen on expanded DES (72%; 23/32), a matching irregularity (n = 18/23) and/or its precursor (n = 11/23) was observed in unexpanded DES. Unexpanded Cypher select showed (small) crater lesions and cracks together with precursors of "peeling." On unexpanded Taxus Liberté, thinning of polymer, small bare metal areas, wrinkles, and one precursor type were found. Unexpanded endeavor showed cracks, small bare metal areas, crater lesions, and precursors of the latter. Unexpanded Xience V and resolute mainly revealed crater lesions and their precursors. On unexpanded versus expanded DES, there was no difference in measured frequency of coating irregularities and precursors (P = ns) with the exception of more bare metal areas on expanded Taxus Liberte (P = 0.01). CONCLUSIONS: Most coating irregularities, or the potential to develop them, are inherent to the unexpanded DES. Important determinants of the formation of coating irregularities may be the stent geometry and the physical properties of the coating, while stent-balloon interaction plays no major role.

Incidence of periprocedural myocardial infarction following stent implantation: comparison between first- and second-generation drug-eluting stents.

BACKGROUND: First- and second-generation drug-eluting stents (DES) differ in coating materials, which may influence the incidence of periprocedural myocardial infarction (PMI). OBJECTIVE: To compare the incidence of PMI between first- and second-generation DES, using the current Academic Research Consortium (ARC) definition of PMI. METHODS: We assessed 800 patients treated with first- (Taxus Liberté or Endeavor) or second-generation DES (Xience V or Resolute). Each DES group consisted of 200 consecutive patients, who were treated during the transition from first- to second-generation DES. Routine peri-interventional assessment of cardiac biomarkers was performed to compare the incidence of PMI between DES groups according to the updated definition by the ARC: 2x upper reference limit of creatine kinase (CK), confirmed by CK-MB elevation. RESULTS: In 800 patients, a total of 1,522 DES (363 Taxus; 385 Endeavor; 382 Xience V; 392 Resolute) were implanted to treat 1,232 lesions. Patient characteristics did not differ between groups. In patients receiving second-generation DES, more multivessel percutaneous coronary interventions were performed (P = 0.01). The overall incidence of PMI was 4.75%. Between first- and second-generation DES, there was no significant difference in PMI (5.5% vs. 4.0%; P = 0.29). In a multivariate analysis, only the total number of stents implanted (P < 0.001) and presentation with acute coronary syndrome (P = 0.02) were independent predictors of PMI. CONCLUSION: Using the revised ARC definition, we found no significant difference in PMI between first- and second-generation DES. Overall, PMI occurred in 4.75%, which is 58% lower than with use of the historical PMI definition.

Effect of oversized partial postdilatation on coatings of contemporary durable polymer-based drug-eluting stents: a scanning electron microscopy study.

BACKGROUND: Oversized postdilation of drug-eluting stents (DES) is often performed to avoid stent malapposition. In stents implanted in long lesion or major bifurcations, extremely oversized partial postdilation may be required, which exposes DES coating to extreme forces. This study aims to assess shape and incidence of coating irregularities on durable polymer-based DES following extremely oversized partial postdilatation. METHODS: Fifteen DES samples (3 3.5 mm stents of Cypher Select plus [Cordis Europa, Roden, the Netherlands], Taxus Liberté[Boston Scientific Corp., Natick, MA, USA], Endeavor Sprint [Medtronic Vascular, Santa Rosa, CA, USA], Endeavor Resolute [Medtronic Vascular, Santa Rosa, CA, USA], and Xience V [Abbott Vascular, Santa Clara, CA, USA]) were deployed in sterile water (37 °C) at 14 atm, followed by a proximal postdilation with noncompliant 5.0-mm balloons at 18 atm. Stents were then examined with scanning electron microscopy. RESULTS: Thorough examination of a total of 660 scanning electron microscopic images demonstrated that shape and incidence of coating irregularities in the postdilated and/or transitional DES regions differed only mildly from the nonpostdilated regions. Cypher Select plus showed more peeling without bare metal aspect in the postdilated and transitional regions, and cracks were wider (P < 0.001) in the postdilated and transitional regions; in Taxus Liberté one additional irregularity (torn webbing) and more wrinkles were observed (P < 0.05 for both); in Endeavor Resolute wider cracks were found in the extremely postdilated region only (P < 0.001). Endeavor Sprint and Xience V showed no differences in shape or incidence of coating irregularities between oversized and nonoversized stent regions. CONCLUSIONS: Bench side assessment of five contemporary durable polymer-based DES with scanning electron microscopy suggests that even very aggressive stent postdilatation results in no more than mild differences in coating irregularities between postdilated and nonpostdilated stent regions.

"Silent" Diabetes and Clinical Outcome After Treatment With Contemporary Drug-Eluting Stents: The BIO-RESORT Silent Diabetes Study.

OBJECTIVES: This study sought to assess the prevalence and clinical impact of silent diabetes and pre-diabetes in "nondiabetic" percutaneous coronary intervention (PCI) all-comers. BACKGROUND: Patients with undetected and thus untreated (silent) diabetes may have higher event risks after PCI with contemporary drug-eluting stents (DES). METHODS: The BIO-RESORT Silent Diabetes study, performed at Thoraxcentrum Twente, is a substudy of the randomized multicenter BIO-RESORT (BIOdegradable Polymer and DuRable Polymer Drug-eluting Stents in an All COmeRs PopulaTion) trial (NCT01674803). Patients underwent oral glucose tolerance testing (OGTT), and assessment of glycosylated hemoglobin with fasting plasma glucose. Primary endpoint was a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization at 1 year. RESULTS: Of the 988 participants, OGTT detected silent diabetes in 68 (6.9%), pre-diabetes in 133 (13.3%), and normal glucose metabolism in 788 (79.8%). Patients with silent diabetes had higher primary endpoint rates (13.2% vs. 7.6% vs. 4.8%; p < 0.001; silent diabetes vs. normal: hazard ratio: 4.2; 95% confidence interval: 1.9 to 9.2). Differences were driven by myocardial infarction (p < 0.001) which occurred mostly <48 h. Based on glycosylated hemoglobin and fasting plasma glucose, silent diabetes was found in 33 (3.3%) patients, pre-diabetes in 217 (22.0%) patients, and normal glucose metabolism in 738 (74.7%) patients; primary endpoint rates were similar to OGTT-based analyses (12.1% vs. 5.5% vs. 3.1%; p = 0.01). Multivariate analyses demonstrated that abnormal glucose metabolism by either diagnostic approach, present in 330 (33.4%) patients, independently predicted adverse event risk (hazard ratio: 2.2; 95% confidence interval: 1.2 to 4.2). CONCLUSIONS: Abnormal glucose metabolism was detected in 1 of 3 "nondiabetic" PCI patients and was independently associated with up to 4-fold higher event risks. Future intervention trials should determine whether meaningful benefits accrue from routine glycemia testing in such patients.

5-Year Outcome Following Randomized Treatment of All-Comers With Zotarolimus-Eluting Resolute Integrity and Everolimus-Eluting PROMUS Element Coronary Stents: Final Report of the DUTCH PEERS (TWENTE II) Trial.

OBJECTIVES: The study sought to evaluate for the first time the 5-year outcomes after treating an all-comers population with newer-generation cobalt chromium-based Resolute Integrity zotarolimus-eluting stents (ZES) (Medtronic, Santa Rosa, California) versus platinum chromium-based PROMUS Element everolimus eluting stents (EES) (Boston Scientific, Natick, Massachusetts). BACKGROUND: The DUTCH PEERS (TWENTE II) (DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity: TWENTE II) trial is a randomized, multicenter, single-blinded, investigator-initiated all-comers trial that found at its main analysis similar 1-year safety and efficacy for both drug-eluting stents. It is the first randomized trial ever to investigate the Resolute Integrity ZES and the first trial to compare both devices. METHODS: In total, 1,811 patients were 1:1 randomized to ZES versus EES. We performed a pre-specified assessment of the 5-year clinical outcomes in terms of safety and efficacy. The main endpoint target vessel failure (TVF) is a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Secondary endpoints included the individual components of TVF, and stent thrombosis. The study was independently monitored, and adverse clinical events were independently adjudicated. RESULTS: Five-year clinical follow-up data was available in 1,798 (99.3%) patients. The ZES and EES groups showed favorable outcomes, with similar 5-year incidence of TVF (13.2% vs. 14.2%; plog-rank = 0.62) and its individual components: cardiac death (4.5% vs. 4.9%; plog-rank = 0.69), target vessel-related myocardial infarction (3.1% vs. 2.6%; plog-rank = 0.47), and target vessel revascularization (7.6% vs. 8.6%; plog-rank = 0.46). The 5-year incidence of definite or probable stent thrombosis was similar (1.5% vs. 1.3%; plog-rank = 0.83). CONCLUSIONS: At 5-year follow-up, the Resolute Integrity ZES and PROMUS Element EES showed similar and sustained results in terms of safety and efficacy for treating a broad population of all-comers.

Five-Year Outcome After Implantation of Zotarolimus- and Everolimus-Eluting Stents in Randomized Trial Participants and Nonenrolled Eligible Patients: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Long-term follow-up after a clinical trial of 2 often-used, newer-generation drug-eluting stents (DESs) in a broad patient population is of interest. Comprehensive long-term outcome of eligible nonenrolled patients has never been reported. Objective: To assess 5-year safety and efficacy of 2 newer-generation DESs in randomized participants with non-ST-elevation acute coronary syndromes or stable angina and to evaluate long-term outcomes of nonenrolled eligible patients treated with the same DESs. Design, Setting, and Participants: The TWENTE (Real-World Endeavor Resolute vs Xience V Drug-Eluting Stent Study in Twente) trial is an investigator-initiated, patient-blinded, randomized, comparative DES trial that enrolled patients from June 18, 2008, to August 26, 2010. Most patients had non-ST-elevation acute coronary syndromes and complex lesions. Of all 1709 eligible patients, 1391 (81.4%) were treated in the TWENTE trial with zotarolimus-eluting (ZES, n = 697) or everolimus-eluting (EES, n = 694) cobalt-chromium stents. The remaining 318 eligible patients (18.6%) were not enrolled but underwent nonrandomized treatment with the same DESs. Data were analyzed from August 26, 2015, to October 11, 2016. Event rates (percentages) were derived from log-rank analysis and may differ from straightforward calculation (nominator/denominator). The 5-year follow-up of the TWENTE participants was prespecified in the trial protocol; that of the nonenrolled participants was ad hoc. Main Outcomes and Measures: Target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Results: Of 1709 eligible participants, 1233 (72.1%) were men, 476 (27.9%) were women, and mean (SD) age was 64.6 (10.6) years. Among the 1370 of 1391 TWENTE trial participants (98.5% follow-up), TVF was similar between those in the ZES (16.1%) and EES (18.1%) groups (P = .36). Stent thrombosis rates were low: definite (7 of 697 [1.0%] vs 4 of 694 [0.6%]; P = .37) and occurred after more than 1 year in 3 (0.4%) with ZES vs 4 (0.6%) with EES (P = .69). The 318 nonenrolled eligible patients (308 patients [96.9%] of whom were followed up) were older and had more advanced disease than trial participants. Their TVF rate was higher than that of trial participants (71 of 318 [23.3%] vs 233 of 1391 [17.1%]; P = .02), which partly reflects a difference in cardiac mortality (23 of 318 [7.7%] vs 60 of 1391 [4.5%]; P = .03). Similar 5-year rates were found for myocardial infarction (91 of 1391 [6.7%] vs 22 of 318 [7.2%]; P = .80) and target vessel revascularization (129 of 1391 [9.7%] vs 34 of 318 [11.4%]; P = .36) between trial participants and nonenrolled eligible patients. In all eligible patients (ie, trial participants plus nonenrolled eligible patients), the TVF rate was only slightly higher than in trial participants only (18.3% vs 17.1%). Conclusions and Relevance: Long-term outcome data from nonenrolled eligible patients support the validity of the TWENTE trial findings and present, with the trial, a strong case for the long-term safety and efficacy of the newer-generation DESs used. Trial Registration: clinicaltrials.gov Identifier: NCT01066650.

Safety and efficacy of everolimus-eluting bioresorbable vascular scaffolds versus durable polymer everolimus-eluting metallic stents assessed at 1-year follow-up: A systematic review and meta-analysis of studies.

BACKGROUND: The Absorb bioresorbable vascular scaffold (BVS) was developed to address long-term safety issues of metallic drug-eluting stents. However, it may be associated with an increased event risk during the first year. METHODS: A systematic literature search was performed (in MEDLINE/PubMed, Cochrane CENTRAL, EMBASE, and scientific meeting abstracts) to identify studies that compared BVS and cobalt-chromium durable polymer everolimus-eluting stents (EES). For randomized clinical trials and non-randomized propensity score matched studies that reported 1-year outcome data, fixed/random-effects models were used to generate pooled estimates of outcomes, presented as odds ratios (OR) with 95%-confidence intervals (CI). RESULTS: The 1-year follow-up data of 6 trials with 5588 patients were analyzed. A device-oriented composite endpoint (DOCE - cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization (TLR)) was reached by 308 BVS or EES patients (195/3253 vs. 113/2315). Meta-analysis showed that patients who received BVS had an increased risk of MI (4.3% vs. 2.3%; OR:1.63, 95%-CI: 1.18-2.25, p<0.01) and definite-or-probable scaffold thrombosis (1.3% vs. 0.6%; OR:2.10, 95%-CI: 1.13-3.87, p=0.02). However, there was no significant between-group difference in risk of DOCE (6.0% vs. 4.9%; OR:1.19, 95%-CI: 0.94-1.52, p=0.16), cardiac death (0.8% vs. 0.7%; OR:1.14, 95%-CI: 0.54-2.39, p=0.73), or TLR (2.5% vs. 2.5%; OR: 0.98, 95%-CI:0.69-1.40, p=0.92). CONCLUSIONS: During the first year of follow-up, patients treated with BVS had a higher incidence of MI and scaffold thrombosis. The risk of DOCE was not significantly different. As BVS may pay off later, future robust data on long-term clinical outcome will be of paramount importance.

Value of the SYNTAX score for periprocedural myocardial infarction according to WHO and the third universal definition of myocardial infarction: insights from the TWENTE trial.

AIMS: The SYNTAX score is a tool to quantify the complexity of coronary artery disease. We investigated the relation between the SYNTAX score and the occurrence of a periprocedural myocardial infarction (PMI) according to the historical definition of the World Health Organization (WHO) and the recently updated universal definition of MI. METHODS AND RESULTS: The SYNTAX score was calculated in 1,243 patients enrolled in TWENTE, a randomised trial which assessed second-generation drug-eluting stents. PMI was defined by the WHO definition and the third universal definition of MI. Patients were divided into tertiles of the SYNTAX score: ≤7 (n=430); >7 and <15 (n=390); ≥15 (n=423). PMI according to the WHO definition occurred more frequently in patients in the highest SYNTAX score tertile (7.3% vs. 3.1% vs. 1.6%, p<0.001) compared to the mid and lowest tertile. Similar findings were seen for universal PMI (9.9% vs. 7.7% vs. 3.7%, p<0.01). After multivariate analysis, SYNTAX score was a significant independent correlate of PMI for both definitions: the highest SYNTAX score tertile had an almost five times higher risk for WHO PMI, and a three times higher risk for universal PMI. CONCLUSIONS: In a broad patient population treated with second-generation DES, the SYNTAX score was able to stratify the risk of PMI.

Safety of second-generation drug-eluting stents three years after randomised use in the TWENTE trial.

AIMS: To assess three-year clinical outcome following randomised use of the second-generation Resolute zotarolimus-eluting stent (ZES) and the XIENCE V everolimus-eluting stent (EES). For Resolute ZES and randomised use, outcome data ≥3 years are relatively scarce. METHODS AND RESULTS: The TWENTE trial examined 1,391 patients with stable angina or non-ST-elevation acute coronary syndromes, of whom 21.6% were diabetics, 70.1% had complex B2 or C lesions and 77.4% had "off-label" indications for DES use. Three-year follow-up data were obtained in 1,381 patients (99.3%; 10 withdrawals). Adverse clinical events were independently adjudicated. The primary endpoint target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction and clinically indicated target vessel revascularisation, was 12.1% for Resolute ZES and 13.4% for XIENCE V EES (p=0.50). Cardiac death rates were 1.9% vs. 3.5% (p=0.06); the other individual components of TVF also showed no significant between-group differences. The rates of definite-or-probable stent thrombosis (1.4% vs. 1.6%, p=0.82) and very late stent thrombosis (0.6% vs. 0.4%, p=1.0) did not differ between the groups. CONCLUSIONS: Three-year follow-up data of patients included in the randomised TWENTE trial demonstrated similar and sustained safety and efficacy of Resolute ZES and XIENCE V EES.

Coronary artery dominance and the risk of adverse clinical events following percutaneous coronary intervention: insights from the prospective, randomised TWENTE trial.

AIMS: To investigate the prognostic value of coronary dominance for various adverse clinical events following the implantation of drug-eluting stents. METHODS AND RESULTS: We assessed two-year follow-up data of 1,387 patients from the randomised TWENTE trial. Based on the origin of the posterior descending coronary artery, coronary circulation was categorised into left and non-left dominance (i.e., right and balanced). Target vessel-related myocardial infarction (MI) was defined according to the updated Academic Research Consortium (ARC) definition (2x upper reference limit of creatine kinase [CK], confirmed by CK-MB elevation), and periprocedural MI (PMI) as MI ≤48 hours following PCI. One hundred and thirty-six patients (9.8%) had left and 1,251 (90.2%) non-left dominance. Target lesions were more frequently located in dominant arteries (p<0.005). Left dominance was associated with more severe calcifications (p=0.006) and more bifurcation lesions (p=0.031). Non-left dominance tended to be less frequent in men (p=0.09). Left coronary dominance was associated with more target vessel-related MI (14 [10.3%] vs. 62 [5.0%], p=0.009). Left dominance independently predicted PMI (adjusted HR 2.19, 95% CI: 1.15-4.15, p=0.017), while no difference in other clinical endpoints was observed between dominance groups. CONCLUSIONS: In the population of the TWENTE trial, we observed a higher incidence of periprocedural myocardial infarction in patients who had left coronary dominance.