Bioresorbable Polymer-Coated Orsiro Versus Durable Polymer-Coated Resolute Onyx Stents (BIONYX): Rationale and design of the randomized TWENTE IV multicenter trial.

AIM: The aim was to compare in a noninferiority trial the efficacy and safety of 2 contemporary drug-eluting stents (DESs): a novel, durable polymer-coated stent versus an established bioabsorbable polymer-coated stent. METHODS AND RESULTS: The BIONYX trial (ClinicalTrials.gov-no.NCT02508714) is an investigator-initiated, prospective, randomized, patient- and assessor-blinded, international, multicenter study in all-comer patients with all types of clinical syndromes and lesions who require percutaneous coronary interventions with DES. Patients at 7 study sites in the Netherlands, Belgium, and Israel were randomly assigned (1:1, stratified for gender and diabetes mellitus) to treatment with the novel, zotarolimus-eluting, durable polymer-coated Resolute Onyx stent that has a radiopaque, thin-strut, CoreWire stent platform versus the sirolimus-eluting, bioresorbable polymer-coated Orsiro stent (reference device) that has a very thin-strut, cobalt-chromium stent backbone. The primary end point is the 1-year incidence of the composite clinical end point target vessel failure consisting of cardiac death, target vessel-related myocardial infarction, or clinically indicated target vessel revascularization. A power calculation, assuming a target vessel failure rate of 6.0% (noninferiority margin 2.5%), revealed that 2,470 study patients would give the study 80% power (α level 5%), allowing for up to 3% loss to follow-up. The first patient was enrolled on October 7, 2015; on December 23, 2016, the last patient entered the study. CONCLUSIONS: BIONYX is a large-scale, prospective, randomized, international, multicenter trial comparing a novel DES with durable coating versus a reference DES with biodegradable coating in all-comers. The study is the first randomized assessment of the Resolute Onyx stent, which is an often-used DES outside the United States.

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.

"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.

Long-Term Outcome of Consecutive Patients With Previous Coronary Bypass Surgery, Treated With Newer-Generation Drug-Eluting Stents.

BACKGROUND: Percutaneous coronary intervention (PCI) in patients with previous coronary artery bypass grafting (CABG) is associated with adverse clinical events. Although newer generation drug-eluting stents showed favorable short-term safety profiles, there is a lack of long-term outcome data. We evaluated the impact of previous CABG on 5-year clinical outcomes of patients treated with PCI using newer-generation drug-eluting stents. METHODS AND RESULTS: In this patient-level pooled analysis of the prospective TWENTE (The Real-World Endeavor Resolute versus Xience V Drug-Eluting Stent Study in Twente) trial and nonenrolled TWENTE registry, we assessed a consecutive series of patients who underwent PCI with newer-generation drug-eluting stents for non-ST-segment-elevation acute coronary syndromes or stable angina. Of all 1709 patients, 202 (11.8%) had a history of CABG. Patients with previous CABG had significantly higher 5-year rates of cardiac death (10.4% versus 4.3%; P<0.001) and target vessel revascularization (25.0% versus 8.1%; P<0.001). These differences remained statistically significant after adjustment for differences in baseline characteristics. Landmark analysis revealed that from 1- to 5-year follow-up, the rates of cardiac death (8.1% versus 3.2%; P<0.001) and target vessel revascularization (17.1% versus 5.9%; P<0.001) were significantly higher in patients with previous CABG. Among patients with a history of CABG, PCI of an obstructed vein graft was associated with a higher rate of 5-year target vessel revascularization (P=0.003). CONCLUSIONS: At 5-year follow-up after PCI with newer-generation drug-eluting stents, the risk of cardiac death and target vessel revascularization was significantly higher in patients with previous CABG. The target vessel revascularization rate was highest in patients who underwent PCI of obstructed vein grafts.

Prediabetes and its impact on clinical outcome after coronary intervention in a broad patient population.

AIMS: It is unclear whether detection of prediabetes (pre-DM) by routine assessment of glycated haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) among patients undergoing percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES) may help identify subjects with increased event risk. We assessed the relation between glycaemia status and one-year outcome after PCI. METHODS AND RESULTS: Glycaemia status was determined in 2,362 non-diabetic BIO-RESORT participants, treated at all four study sites, to identify pre-DM (HbA1c 42-47 mmol/mol; FPG 6.1-6.9 mmol/L) and unknown diabetes mellitus (DM) (HbA1c ≥48 mmol/mol; FPG ≥7.0 mmol/L). Another 624 patients had medically treated DM. The main composite endpoint consisted of death, myocardial infarction, or revascularisation. Glycaemic state was known in 2,986 participants: 324 (11%) patients had pre-DM, 793 (27%) had DM (known or new), and 1,869 (63%) patients had normoglycaemia. Pre-DM and DM patients differed from normoglycaemic patients in cardiovascular risk factors. The composite endpoint occurred in 11.1% in pre-DM, 10.5% in DM, and 5.7% in normoglycaemia (p<0.001). Pre-DM was associated with a twofold higher event risk compared to normoglycaemia (adj. HR 2.0, 95% CI: 1.4-3.0). CONCLUSIONS: Following PCI with contemporary DES, all-comers with pre-DM had significantly higher event risks than normoglycaemic patients. In non-DM patients requiring PCI, routine assessment of HbA1c and FPG appears to be of value to identify subjects with increased event risk.

Clopidogrel or ticagrelor in acute coronary syndrome patients treated with newer-generation drug-eluting stents: CHANGE DAPT.

AIMS: Acute coronary syndrome (ACS) guidelines have been changed, favouring more potent antiplatelet drugs. We aimed to evaluate the safety and efficacy of a ticagrelor- instead of a clopidogrel-based primary dual antiplatelet (DAPT) regimen in ACS patients treated with newer-generation drug-eluting stents (DES). METHODS AND RESULTS: CHANGE DAPT (clinicaltrials.gov: NCT03197298) assessed 2,062 consecutive real-world ACS patients, treated by percutaneous coronary intervention (PCI), the primary composite endpoint being net adverse clinical and cerebral events (NACCE: all-cause death, any myocardial infarction, stroke or major bleeding). In the clopidogrel (CP; December 2012-April 2014) and ticagrelor periods (TP; May 2014-August 2015), 1,009 and 1,053 patients were treated, respectively. TP patients were somewhat older, underwent fewer transfemoral procedures, and received fewer glycoprotein IIb/IIIa inhibitors. In the TP, the one-year NACCE rate was higher (5.1% vs. 7.8%; HR 1.53 [95% CI: 1.08-2.17]; p=0.02). Assessment of non-inferiority (pre-specified margin: 2.7%) was inconclusive (risk difference: 2.64 [95% CI: 0.52-4.77]; pnon-inferiority=0.48). TP patients had more major bleeding (1.2% vs. 2.7%; p=0.02) while there was no benefit in ischaemic endpoints. Propensity score-adjusted multivariate analysis confirmed higher NACCE (adj. HR 1.75 [95% CI: 1.20-2.55]; p=0.003) and major bleeding risks during TP (adj. HR 2.75 [95% CI: 1.34-5.61]; p=0.01). CONCLUSIONS: In this observational study, the guideline-recommended ticagrelor-based primary DAPT regimen was associated with an increased event risk in consecutive ACS patients treated with newer-generation DES.

Three-Year Clinical Outcome of Patients with Coronary Disease and Increased Event Risk Treated with Newer-Generation Drug-Eluting Stents: From the Randomized DUTCH PEERS Trial.

OBJECTIVE: Limited data is available on the long-term outcome of patients with increased cardiovascular event risk, treated with newer-generation durable polymer drug-eluting stents (DES). METHODS: We therefore assessed 3-year follow-up data of high-risk versus low- to intermediate-risk patients of the randomized DUTCH PEERS trial (NCT01331707). In both risk groups we also compared patients treated with Resolute Integrity versus Promus Element DES. Patients were categorized as "high-risk" if they met ≥1 of the following criteria: (1) diabetes (17.9%); (2) previous myocardial infarction (21.9%); (3) previous coronary revascularization (25.8%); (4) chronic renal failure (3.5%); (5) left ventricular ejection fraction ≤30% (1.5%); and (6) age ≥75 years (17.3%). RESULTS: At the 3-year follow-up, the incidence of the composite endpoint target vessel failure (TVF) (13.2 vs. 7.5%; logrank p < 0.001) and 2 of its components - cardiac death (4.7 vs. 1.5%; logrank p < 0.001) and target vessel revascularization (7.3 vs. 4.7%; logrank p = 0.03) - was higher in high-risk (n = 957) versus low- to intermediate-risk patients (n = 854). Among high-risk patients, treatment with Resolute Integrity (n = 481) and Promus Element stents (n = 476) was similarly safe and efficacious (TVF: 13.3 vs. 13.1%; logrank p = 0.95; definite-or-probable stent thrombosis: 1.7 vs. 1.7%; logrank p = 1.00). CONCLUSIONS: The newer-generation Resolute Integrity and Promus Element stents showed similar results in terms of safety and efficacy for treating high-risk patients, who had significantly higher event rates than patients with low-to-intermediate risk.

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.

Three-year safety and efficacy of treating all-comers with newer-generation Resolute Integrity or PROMUS Element stents in the randomised DUTCH PEERS (TWENTE II) trial.

AIMS: The aim of this report was to assess the three-year safety and efficacy of implanting newer-generation Resolute Integrity zotarolimus-eluting stents (ZES) versus PROMUS Element everolimus-eluting stents (EES) in all-comers. METHODS AND RESULTS: In the randomised, multicentre, investigator-initiated DUTCH PEERS trial, a total of 1,811 all-comers were 1:1 randomly assigned to treatment with ZES versus EES. A total of 1,293 patients (72%) were treated for complex lesions and 455 patients (25%) were treated for multiple lesions. The primary endpoint target vessel failure (TVF) is a composite of cardiac death, target vessel-related myocardial infarction or target vessel revascularisation. Adverse clinical events were independently adjudicated. Three-year follow-up data were obtained in 1,807 patients (99.8%, four withdrawals). Both the ZES and EES groups showed favourable outcomes with a similar incidence of TVF (10.7% vs. 10.3%; pLog-rank=0.77) and the individual components thereof: cardiac death (3.2% vs. 3.1%; pLog-rank=0.87), target vessel-related myocardial infarction (2.8% vs. 2.2%; pLog-rank=0.44) and target vessel revascularisation (6.0% vs. 6.2%; pLog-rank=0.87). In addition, the incidence of definite or probable stent thrombosis was similar for patients treated with ZES versus EES (1.4% vs. 1.1%; pLog-rank=0.66). CONCLUSIONS: The safety and efficacy of treating all-comers with newer-generation Resolute Integrity and PROMUS Element stents was found to be extended up to three years.

Two-year outcome after treatment of severely calcified lesions with newer-generation drug-eluting stents in acute coronary syndromes: A patient-level pooled analysis from TWENTE and DUTCH PEERS.

BACKGROUND: Data on medium-term outcome of patients with acute coronary syndrome (ACS), treated with newer-generation durable polymer drug-eluting stents (DES) in severely calcified coronary lesions, are scarce. We aimed to assess the impact of severe coronary lesion calcification on clinical outcome of patients with ACS, treated with newer-generation DES. METHODS: The TWENTE and DUTCH PEERS randomized trials comprise 1779 ACS patients, who were categorized into patients with versus without severe target lesion calcification. We performed a patient-level pooled analysis to assess 2-year outcome, including target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction (MI), or target vessel revascularization (TVR). RESULTS: Patients with severe target lesion calcification (n=340, 19.1%) were older (66.8±10.6 years vs. 62.8±11.5 years, p<0.001) and had more often diabetes (22.1% vs. 16.8%, p=0.02) and hypercholesterolemia (51.5% vs. 42.9%, p=0.005) than other patients (n=1439, 79.9%). In addition they showed a higher TVF rate (12.4% vs.7.0%, p=0.001), mainly related to a difference in TVR (6.8% vs. 3.3%, p=0.003). There was a borderline significant between-group difference in cardiac death (3.6% vs. 1.8%, p=0.05), but not in target vessel MI (3.8% vs.2.6%, p=0.23) and definite stent thrombosis (0.9% vs. 0.6%, p=0.71). Multivariate analysis demonstrated that severe lesion calcification was an independent risk factor of TVF (adjusted HR; 1.58, 95% CI: 1.23-2.03; p<0.001). CONCLUSIONS: In patients with ACS, treatment of severely calcified lesions with newer-generation DES was associated with an overall higher clinical event risk - related in particular to a higher TVR rate, while the risk of MI was low.

Resultados de los stents Resolute Integrity y Promus Element en el infarto de miocardio: análisis del ensayo aleatorizado DUTCH PEERS (TWENTE II ) / Outcome after myocardial infarction treated with Resolute Integrity and Promus Element stents: insights from the DUTCH PEERS (TWENTE II) randomized trial

Introducción y objetivos: En el infarto agudo de miocardio (IAM), los nuevos stents farmacoactivos (SFA) de alta liberación de fármacos pueden ser de especial utilidad, ya que su diseño flexible podría reducir los traumatismos inducidos por el dispositivo en la lesión culpable. El objetivo del estudio es evaluar la seguridad y la eficacia de las intervenciones coronarias percutáneas con 2 nuevos SFA con recubrimiento de polímero duradero en pacientes con IAM. Métodos: El ensayo multicéntrico prospectivo y aleatorizado DUTCH PEERS (TWENTE II) compara los stents Resolute Integrity y Promus Element en 1.811 pacientes consecutivos no seleccionados (all-comers); a 817 (45,1%) de ellos se los trató por un IAM con o sin elevación del segmento ST y se dispuso de un seguimiento de 2 años del 99,9% de los casos. El objetivo clínico principal es el fallo del vaso diana (FVD), que consiste en la combinación de muerte cardiaca, infarto de miocardio relacionado con el vaso diana y revascularización del vaso diana. Resultados: De los 817 pacientes tratados por un IAM, 421 (51,5%) recibieron un stent Resolute Integrity y 396 (48,5%), un Promus Element. A los 2 años de seguimiento, las tasas de FVD (el 7,4 frente al 6,1%; p = 0,45), revascularización de la lesión diana (el 3,1 frente al 2,8%; p = 0,79) y trombosis del stent definitiva (el 1,0 frente al 0,5%; p = 0,69) fueron bajas en los 2 grupos de stents. En consonancia con estos resultados obtenidos en el conjunto de los pacientes con IAM, los resultados observados con los 2 SFA fueron favorables y similares con ambos dispositivos en 370 pacientes con IAM con elevación del segmento ST (FVD, el 5,1 frente al 4,9%; p = 0,81) y 447 pacientes con IAM sin elevación del segmento ST (FVD, el 9,0 frente al 7,5%; p = 0,56). Conclusiones: Los stents Resolute Integrity y Promus Element fueron seguros y eficaces en el tratamiento de pacientes con IAM. Los datos de seguimiento a 2 años subrayan la seguridad de emplear estos dispositivos en este contexto clínico específico (AU)

Introduction and objectives: In acute myocardial infarction (MI), novel highly deliverable drug-eluting stents (DES) may be particularly valuable as their flexible stent designs might reduce device-induced traumas to culprit lesions. The aim of the study was to assess the safety and efficacy of percutaneous coronary interventions with 2 novel durable polymer-coated DES in patients with acute MI. Methods: The prospective, randomized DUTCH PEERS (TWENTE II) multicenter trial compares Resolute Integrity and Promus Element stents in 1811 all-comer patients, of whom 817 (45.1%) were treated for ST-segment elevation MI or non—ST-segment elevation MI and the 2-year outcome is available in 99.9%. The primary clinical endpoint is target vessel failure (TVF), a composite of cardiac death, target vessel related MI, or target vessel revascularization. Results: Of all 817 patients treated for acute MI, 421 (51.5%) were treated with Resolute Integrity and 396 (48.5%) with Promus Element stents. At the 2-year follow-up, the rates of TVF (7.4% vs 6.1%; P = .45), target lesion revascularization (3.1% vs 2.8%; P = .79), and definite stent thrombosis (1.0% vs 0.5%; P = .69) were low for both stent groups. Consistent with these findings in all patients with acute MI, outcomes for the 2 DES were favorable and similar in both, with 370 patients with ST-segment elevation MI (TVF, 5.1% vs 4.9%; P = .81) and 447 patients with non—ST-segment elevation MI (TVF, 9.0% vs 7.5%; P = .56). Conclusions: Resolute Integrity and Promus Element stents were both safe and efficacious in treating patients with acute MI. The present 2-year follow-up data underline the safety of using these devices in this particular clinical setting (AU)

Very thin strut biodegradable polymer everolimus-eluting and sirolimus-eluting stents versus durable polymer zotarolimus-eluting stents in allcomers with coronary artery disease (BIO-RESORT): a three-arm, randomised, non-inferiority trial.

BACKGROUND: In patients with coronary artery disease, treated with durable polymer-coated drug-eluting stents, the life-long presence of the polymer might delay arterial healing. Novel very thin strut biodegradable polymer stents, which leave only a bare metal stent after polymer resorption, might improve long-term outcome. We investigated in allcomers the safety and efficacy of three stents eluting either everolimus, sirolimus, or zotarolimus, often clinically used but never compared, of which the biodegradable polymer everolimus-eluting stent was never before assessed in allcomers. METHODS: The large-scale, investigator-initiated, multicentre, assessor and patient blinded, three-arm, randomised, BIO-RESORT non-inferiority trial was done at four clinical sites in the Netherlands. All-comer patients were aged 18 years or older, capable of providing informed consent, and required a percutaneous coronary intervention with drug-eluting stent implantation according to clinical guidelines or the operators' judgment. Exclusion criteria were: participation in another randomised drug or device study before reaching the primary endpoint of that study; planned surgery necessitating interruption of dual antiplatelet therapy within the first 6 months; known intolerance to components of the investigational product or medication required; uncertainty about the adherence to follow-up procedures or an assumed life expectancy of less than 1 year; or known pregnancy. Web-based computer-generated allocation sequences randomly assigned patients (1:1:1) to treatment with very thin strut biodegradable polymer everolimus-eluting or sirolimus-eluting stents (which differ substantially in type, amount, distribution, and resorption speed of their respective coating), or thin strut durable polymer zotarolimus-eluting stents. The primary endpoint was a composite of safety (cardiac death or target vessel-related myocardial infarction) and efficacy (target vessel revascularisation) at 12 months of follow up with a very thin strut biodegradable polymer of either everolimus-eluting or sirolimus-eluting stents, compared with durable polymer zotarolimus-eluting stents, analysed by intention to treat (non-inferiority margin 3·5%). This trial was registered with ClinicalTrials.gov, number NCT01674803. FINDINGS: From Dec 21, 2012, to Aug 24, 2015, 3514 patients were enrolled and analysed, of whom 2449 (70%) had acute coronary syndromes, which included 1073 (31%) ST-elevation myocardial infarctions. 12 month follow-up of 3490 (99%) patients (three lost to follow-up; 21 withdrawals) was available. The primary endpoint was met by 55 (5%) of 1172 patients assigned to everolimus-eluting stents, 55 (5%) of 1169 assigned to sirolimus-eluting stents and 63 (5%) of 1173 assigned to zotarolimus-eluting stents. Non-inferiority of the everolimus-eluting stents and sirolimus-eluting stents compared with zotarolimus-eluting stents was confirmed (both -0·7% absolute risk difference, 95% CI -2·4 to 1·1; upper limit of one sided 95% CI 0·8%, pnon-inferiority<0·0001). Definite stent thrombosis (defined by the Academic Research Consortium) occurred in four (0·3%) of 1172 patients who were allocated to everolimus-eluting stents, four (0·3%) of 1169 patients who were allocated to sirolimus-eluting stents, and three (0·3%) of 1173 patients who were allocated to zotarolimus-eluting stents (log-rank p=0·70 for both comparisons with zotarolimus-eluting stents). INTERPRETATION: At 12 month follow-up, both very thin strut drug-eluting stents with dissimilar biodegradable polymer coatings (eluting either everolimus or sirolimus) were non-inferior to the durable polymer stent (eluting zotarolimus) in treating allcomers with a high proportion of patients with acute coronary syndromes. The absence of a loss of 1 year safety and efficacy with the use of these two biodegradable polymer-coated stents is a prerequisite before assessing their potential longer-term benefits. FUNDING: Biotronik, Boston Scientific, and Medtronic.

Outcome After Myocardial Infarction Treated With Resolute Integrity and Promus Element Stents: Insights From the DUTCH PEERS (TWENTE II) Randomized Trial.

INTRODUCTION AND OBJECTIVES: In acute myocardial infarction (MI), novel highly deliverable drug-eluting stents (DES) may be particularly valuable as their flexible stent designs might reduce device-induced traumas to culprit lesions. The aim of the study was to assess the safety and efficacy of percutaneous coronary interventions with 2 novel durable polymer-coated DES in patients with acute MI. METHODS: The prospective, randomized DUTCH PEERS (TWENTE II) multicenter trial compares Resolute Integrity and Promus Element stents in 1811 all-comer patients, of whom 817 (45.1%) were treated for ST-segment elevation MI or non-ST-segment elevation MI and the 2-year outcome is available in 99.9%. The primary clinical endpoint is target vessel failure (TVF), a composite of cardiac death, target vessel related MI, or target vessel revascularization. RESULTS: Of all 817 patients treated for acute MI, 421 (51.5%) were treated with Resolute Integrity and 396 (48.5%) with Promus Element stents. At the 2-year follow-up, the rates of TVF (7.4% vs 6.1%; P = .45), target lesion revascularization (3.1% vs 2.8%; P = .79), and definite stent thrombosis (1.0% vs 0.5%; P = .69) were low for both stent groups. Consistent with these findings in all patients with acute MI, outcomes for the 2 DES were favorable and similar in both, with 370 patients with ST-segment elevation MI (TVF, 5.1% vs 4.9%; P = .81) and 447 patients with non-ST-segment elevation MI (TVF, 9.0% vs 7.5%; P = .56). CONCLUSIONS: Resolute Integrity and Promus Element stents were both safe and efficacious in treating patients with acute MI. The present 2-year follow-up data underline the safety of using these devices in this particular clinical setting.

Small-vessel treatment with contemporary newer-generation drug-eluting coronary stents in all-comers: Insights from 2-year DUTCH PEERS (TWENTE II) randomized trial.

BACKGROUND: Treatment of lesions in small vessels was associated with worse clinical outcome, and various definitions of "small vessels" have been used. Data with novel drug-eluting stents are scarce. METHODS: To compare the outcome of patients with vs without small-vessel treatment, we assessed 2-year follow-up data of the DUTCH PEERS randomized trial (ClinicalTrials.gov: NCT01331707), in which 1,811 all-comers were treated with contemporary zotarolimus-eluting (Resolute Integrity) or everolimus-eluting (Promus Element) stents. Primary end point was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization. RESULTS: The rates of TLF (9.5% vs 5.4%; P log rank = .001) and 2 individual components thereof-target vessel myocardial infarction (3.1% vs 1.3%; P log rank = .006) and target lesion revascularization (4.8% vs 2.8%; P log rank = .02)-were higher among 798 (44.1%) patients treated in at least one small vessel (<2.50 mm by quantitative coronary angiography). Multivariate analysis with propensity score adjustment demonstrated that treatment of small-vessel lesions independently predicted TLF at 2-year follow-up (hazard ratio 1.60, 95% CI 1.09-2.34). Patients with the smallest target vessel being <2.25 mm had TLF rates similar to patients with smallest target vessels of 2.25 to <2.50 mm; however, patients treated in vessels no smaller than 2.50 to <3.00 mm and patients treated in vessels ≥3.00 mm had lower TLF rates (9.3%, 9.8%, 5.0%, and 5.8%, respectively; P log rank = .009). CONCLUSION: Patients treated with novel drug-eluting stents in small-vessel lesions had higher adverse event rates than did patients who had no small-vessel treatment. Our data suggest that with current stents, a vessel diameter <2.50 mm is a suitable threshold to identify small target vessels.

Impact of severe lesion calcification on clinical outcome of patients with stable angina, treated with newer generation permanent polymer-coated drug-eluting stents: A patient-level pooled analysis from TWENTE and DUTCH PEERS (TWENTE II).

BACKGROUND: The outcome of percutaneous coronary intervention with newer generation permanent polymer-coated drug-eluting stents (DES) in patients with severely calcified lesions is greatly unknown. We assessed the impact of severe lesion calcification on clinical outcome in patients with stable angina who underwent percutaneous coronary intervention with newer generation DES. METHODS: TWENTE and DUTCH PEERS randomized trials enrolled 1423 patients with stable angina, who were categorized into patients with versus without severe target lesion calcification. A patient-level pooled analysis assessed clinical outcome, including target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization (TVR). RESULTS: Patients with severe calcification (n = 342) were older (66.6 ± 9.1 vs 64.2 ± 9.8 years, P < .001) and had more diabetes (25.7% vs 20.4%, P = .04) than other patients (n = 1081). Patients with calcified lesions had higher rates of TVF (16.4% vs 9.8%, pLogrank = .001), cardiac death (4.4% vs 1.5%, P = .03), target vessel myocardial infarction (7.6% vs 3.4%, P = .001), and definite stent thrombosis (1.8% vs 0.4%, P = .02). Multivariate analysis demonstrated that severe calcification was an independent risk factor of 2-year TVF (HR 1.42, 95% CI: 1.02-1.99, pLogrank = .04); landmark analysis showed that this was based on a difference during the first year (periprocedural: 5.8% vs. 3.1%, pLogrank = .02; first year: 7.5% vs. 3.8%, pLogrank = .007; second year: 4.1% vs. 3.3%, pLogrank = .54). CONCLUSION: In patients with stable angina, severe target lesion calcification is associated with an increased risk of adverse cardiovascular events following treatment with newer generation permanent polymer-coated DES. This increase in risk is restricted to the first year of follow-up, which is an encouraging finding.

Sex Difference in Chest Pain After Implantation of Newer Generation Coronary Drug-Eluting Stents: A Patient-Level Pooled Analysis From the TWENTE and DUTCH PEERS Trials.

OBJECTIVES: This study sought to assess sex differences in chest pain after percutaneous coronary intervention (PCI) with newer generation drug-eluting stents (DES). BACKGROUND: Sex-based data on chest pain after PCI with DES are scarce. METHODS: The authors performed a patient-level pooled analysis of the TWENTE and DUTCH PEERS randomized trials, in which patients were treated with newer generation permanent polymer-coated DES. At 1 and 2 years, clinical follow-up was available in 99.8% and patient-reported chest pain data in 94.1% and 93.6%, respectively. RESULTS: Among all 3,202 patients, the 871 (27.2%) women were older (67.5 ± 10.2 years vs. 62.8 ± 10.6 years; p < 0.001) and had more cardiovascular risk factors: diabetes (24.2% vs. 17.8%; p < 0.001), hypertension (63.6% vs. 51.6%; p < 0.001), and positive family history (54.5% vs. 50.1%; p = 0.03). At 1- and 2-year follow-up, women reported more clinically relevant chest pain (16.3% vs. 10.5%; p < 0.001, and 17.2% vs. 11.1%; p < 0.001, respectively). Multivariate analysis demonstrated that female sex independently predicted clinically relevant chest pain at 1- and 2-year follow-up both during daily activities and at minimum physical exertion/at rest (1 year adjusted odds ratio [OR]: 1.7; 95% confidence interval [CI]: 1.2 to 2.4; p = 0.002; and adjusted OR: 1.8; 95% CI: 1.3 to 2.5; p < 0.001; 2-year adjusted OR: 1.8; 95% CI: 1.3 to 2.6; p < 0.001; and adjusted OR: 1.7; 95% CI: 1.3 to 2.3; p = 0.001). Nevertheless, the 2-year rates of death, myocardial infarction, revascularization, stent thrombosis, and various composite clinical endpoints were similar for both sexes. CONCLUSIONS: Although the incidence of adverse cardiovascular events was low and similar for both sexes, women showed a statistically significantly higher prevalence of clinically relevant chest pain, which might be largely related to mechanisms other than epicardial coronary obstruction.

Long-term outcome and chest pain in patients with true versus non-true bifurcation lesions treated with second-generation drug-eluting stents in the TWENTE trial.

The objective of this study is to assess 3-year clinical outcome of patients with true bifurcation lesions (TBLs) versus non-true bifurcation lesions (non-TBLs) following treatment with second-generation drug-eluting stents (DES). TBLs are characterized by the obstruction of both main vessel and side-branch. Limited data are available on long-term clinical outcome following TBL treatment with newer-generation DES. We performed an explorative sub-study of the randomized TWENTE trial among 287 patients who had bifurcated target lesions with side-branches ≥2.0 mm. Patients were categorized into TBL (Medina classes: 1.1.1; 1.0.1; 0.1.1) versus non-TBL to compare long-term clinical outcome. A total of 116 (40.4 %) patients had TBL, while 171 (59.6 %) had non-TBL only. Target-lesion revascularization rates were similar (3.5 vs. 3.5 %; p = 1.0), and definite-or-probable stent thrombosis rates were low (both <1.0 %). The target-vessel myocardial infarction (MI) rate was 11.3 versus 5.3 % (p = 0.06), mostly driven by (periprocedural) MI ≤48 h from PCI. All-cause mortality and cardiac death rates were 8.7 versus 3.5 % (p = 0.06) and 3.5 versus 1.2 % (p = 0.22), respectively. The 3-year major adverse cardiac event rate for patients with TBL versus non-TBL was 20.0 versus 11.7 % (p = 0.05). At 1-, 2-, and 3-year follow-up, 6.5, 13.0, and 11.0 % of patients reported chest pain at less than or equal moderate physical effort, respectively, without any between-group difference. Patients treated with second-generation DES for TBL had somewhat higher adverse event rates than patients with non-TBL, but dissimilarities did not reach statistical significance. Up to 3-year follow-up, the vast majority of patients of both groups remained free from chest pain.

Bifurcation treatment with novel, highly flexible drug-eluting coronary stents in all-comers: 2-year outcome in patients of the DUTCH PEERS trial.

BACKGROUND: Percutaneous coronary intervention (PCI) in bifurcated lesions with second-generation drug-eluting stents (DES) was associated with increased myocardial infarction (MI) rates. Flexible stent designs that accommodate well to vessel tapering may be of benefit in challenging anatomies such as bifurcated target lesions, but so far data are scarce. METHODS: We analyzed the 2-year follow-up data of the DUTCH PEERS (TWENTE II) trial, which randomized 1811 all-comer patients to PCI with newer generation resolute integrity zotarolimus-eluting (Medtronic) or promus element everolimus-eluting stents (Boston Scientific). In bifurcated lesions, provisional stenting was generally performed. Target vessel failure is a composite endpoint, consisting of cardiac death, target vessel MI, or target vessel revascularization. RESULTS: Patients with at least one bifurcated lesion (n = 465, 25.7 %) versus patients with non-bifurcated target lesions only (n = 1346, 74.3 %) showed similar rates of clinical endpoints including target vessel failure (9.2 versus 7.9 %, p = 0.36) and definite stent thrombosis (0.4 versus 1.0 %, p = 0.38). Target vessel MI was more common in patients with bifurcated lesions (3.4 versus 1.6 %, p = 0.02); but after multivariate analysis with propensity score adjustment, bifurcation treatment was found not to be an independent predictor of target vessel MI (HR 1.40, 95 % CI 0.71-2.76; p = 0.34). Among patients with bifurcated lesions, DES type and side-branch size did not affect outcome, but periprocedural MI occurred more often after two-stent approaches (9.0 versus 2.1 %; p = 0.002). CONCLUSION: All-comer patients treated for bifurcated and non-bifurcated target lesions showed similar and low rates of clinical endpoints, suggesting that the DES used are efficacious and safe for treating bifurcated target lesions.

Patient preference regarding assessment of clinical follow-up after percutaneous coronary intervention: the PAPAYA study.

AIMS: To keep patients in long-term clinical follow-up programmes after percutaneous coronary intervention (PCI), knowledge of the patient-preferred mode for follow-up assessment is crucial. We systematically assessed patient preference, and explored potential relationships with age and gender. METHODS AND RESULTS: In the prospective, observational PAPAYA study (ClinicalTrials.gov: NCT02189070), 2,566 patients, treated by PCI between June 2008 and May 2012, were invited to participate in a postal survey on the patient-preferred mode (postal questionnaire, telephone or e-mail consultation) and frequency of follow-up assessment. A total of 1,797 (70.0%) patients responded. The vast majority preferred completing postal questionnaires (1,248 [69.9%]) as compared to telephone (240 [13.4%]) or e-mail-based approaches (227 [12.7%]) (p<0.001). With increasing age, there was a gradual decline in preference for e-mail (p<0.001); the youngest patients (≤60 years) preferred e-mail-based follow-up more often than the oldest (21.1% vs. 3.1%). Nevertheless, 79.9% of the youngest preferred to be approached in ways other than by e-mail. Women more often preferred approaches other than e-mail (94.1% vs. 87.3%, p<0.001). CONCLUSIONS: Patients showed a distinct preference for completing postal questionnaires rather than being approached by telephone or e-mail. Younger patients accepted e-mail-based follow-up more often, but the majority of the youngest patients still preferred approaches other than by e-mail.