High bleeding risk patients with acute coronary syndromes treated with contemporary drug-eluting stents and Clopidogrel or Ticagrelor: Insights from CHANGE DAPT.

BACKGROUND: The prospective observational CHANGE DAPT study compared clopidogrel versus ticagrelor-based dual antiplatelet (DAPT) regimens in consecutive patients with acute coronary syndrome (ACS), treated with percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES). During the ticagrelor period (TP, May 2014-August 2015) there were more major bleedings than during the clopidogrel period (CP, December 2012-April 2014). METHODS AND RESULTS: To evaluate whether the excess of major bleedings during TP may be limited to high bleeding risk (HBR) patients, we performed an explorative analysis of all 2062 CHANGE DAPT participants, of whom 547(26.5%) were classified as HBR (CP, n = 245; TP, n = 302). In HBR and non-HBR patients, we assessed the impact of CP versus TP on propensity score-adjusted rates of major bleeding and a pre-defined ischemic endpoint (composite of cardiac death, myocardial infarction, or stroke) at 1-year follow-up. Among HBR patients, the rate of major bleeding was significantly higher during TP (1.7% vs. 5.0%; HRadjusted 3.70 [95% CI 1.18-11.67], p = 0.03), while there was no significant difference in the ischemic endpoint (6.6% vs. 8.0%, HRadjusted 1.23 [95% CI 0.63-2.42], p = 0.54). In non-HBR patients, the rates of major bleeding (1.1% vs. 1.7%; HRadjusted 2.13 [95% CI 0.84-5.43], p = 0.11) and the ischemic endpoint (2.8% vs. 3.4%, HRadjusted 1.38 [95% CI 0.74-2.57], p = 0.32) were similar between both periods. CONCLUSIONS: Among consecutive ACS patients, the increased risk of major bleeding during ticagrelor-based DAPT was limited to HBR patients. In both HBR and non-HBR patients, ticagrelor-based DAPT did not reduce ischemic outcomes following treatment with contemporary DES implantation.

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.

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.

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.

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.

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.

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.

Clinical Events and Patient-Reported Chest Pain in All-Comers Treated With Resolute Integrity and Promus Element Stents: 2-Year Follow-Up of the DUTCH PEERS (DUrable Polymer-Based STent CHallenge of Promus ElemEnt Versus ReSolute Integrity) Randomized Trial (TWENTE II).

OBJECTIVES: This study assessed clinical events and patient-reported chest pain 2 years after treatment of all-comers with Resolute Integrity zotarolimus-eluting stents (Medtronic Vascular, Santa Rosa, California) and Promus Element everolimus-eluting stents (Boston Scientific, Natick, Massachusetts). BACKGROUND: For both drug-eluting stents (DES), no all-comer outcome data from >12 months of follow-up have been published. Although there is increasing interest in patient-reported chest pain following stenting, data with novel DES are scarce. METHODS: The DUTCH PEERS multicenter trial (TWENTE II) (DUrable Polymer-Based STent CHallenge of Promus ElemEnt Versus ReSolute Integrity) Randomized Trial [TWENTE II]) randomized 1,811 all-comer patients to treatment with 1 type of DES. Monitoring and event adjudication were performed by independent contract research organizations. RESULTS: The 2-year follow-up of 1,810 patients (99.9%) was available. The primary composite endpoint target vessel failure occurred in 8.6% and 7.8% of patients treated with zotarolimus- and everolimus-eluting stents, respectively (p = 0.55). Rates of components of target vessel failure were: cardiac death (2.4% vs. 1.9%, p = 0.42); target vessel-related myocardial infarction (2.4% vs. 1.8%, p = 0.33); clinically-indicated target vessel revascularization (4.6% vs. 4.9%, p = 0.83). At 1- and 2-year follow-up, >80% of patients were free from chest pain (no between-stent difference). In addition, >87% of patients were either free from chest pain or experienced pain only at maximal physical exertion, but not during normal daily activities. Patients with chest pain after 12 months at no more than moderate physical effort had a higher risk of target vessel revascularization during the following year (hazard ratio: 1.89 [95% confidence interval: 1.05 to 3.39], p = 0.03). CONCLUSIONS: During the second year of follow-up, the incidence of adverse clinical endpoints remained similar and low for both DES. The vast majority of patients were free from chest pain.

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.

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.

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.

Clinical outcome following second-generation drug-eluting stent use for off-label versus on-label indications: insights from the two-year outcome of the TWENTE trial.

AIMS: Drug-eluting stents (DES) were first used on-label - in simple patients with low clinical risk and easily accessible lesions. Currently, DES are increasingly used off-label - in complex patients undergoing percutaneous coronary interventions (PCI) with historically higher event risk. Therefore, our aim was to investigate whether patients with off-label indications for DES use had similar outcomes compared to patients who were treated for on-label indications only. We analysed two-year follow-up data of 1,387 TWENTE trial patients, treated with second-generation everolimus-eluting XIENCE V or zotarolimus-eluting Resolute stents, and compared off-label vs. on-label DES use with regard to the following clinical endpoints: cardiac death, myocardial infarction (MI), periprocedural MI (≤48 hrs), and target vessel revascularisation (TVR). Patients with off-label DES use (n=1,033; 74.5%) had more diabetes (22.9% vs. 17.5%; p=0.032), previous MI (35.9% vs. 22.3%; p<0.001), type B2/C lesions (84.7% vs. 62.7%; p<0.001), and acute coronary syndromes (57.8% vs. 33.3%; p<0.001). Nevertheless, cardiac death and TVR rates were similar to those of patients with on-label DES use (p>0.8). Following off-label DES use, there was a higher incidence of PMI (5.0% vs. 1.4%; p=0.003), of which only 1.1% reached creatine kinase levels >5x the upper limit of normal (ULN). Despite differences in risk profile, patients with off-label DES use did not differ from patients with on-label DES use in clinical endpoints other than periprocedural MI. These largely positive findings underline the favourable safety profile of second-generation DES.

Clinical outcome following stringent discontinuation of dual antiplatelet therapy after 12 months in real-world patients treated with second-generation zotarolimus-eluting resolute and everolimus-eluting Xience V stents: 2-year follow-up of the randomized TWENTE trial.

OBJECTIVES: The aim of this study was to assess the safety and efficacy of the implantation of Resolute zotarolimus-eluting stents (ZES) (Medtronic Inc., Santa Rosa, California) and Xience V everolimus-eluting stents (EES) (Abbott Vascular, Santa Clara, California) following strict discontinuation of dual antiplatelet therapy (DAPT) after 12 months. BACKGROUND: Only limited long-term follow-up data are available from head-to-head comparisons of second-generation drug-eluting stents. METHODS: The randomized TWENTE (The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twente) trial is an investigator-initiated study performed in a population with many complex patients and lesions and only limited exclusion criteria. Patients were randomly assigned 1:1 to ZES (n = 697) or EES (n = 694). RESULTS: Two-year follow-up information was available on all patients. The rate of continuation of DAPT beyond 12 months was very low (5.4%). The primary endpoint of target vessel failure, a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization, did not differ between ZES and EES (10.8% vs. 11.6, p = 0.65), despite fewer target lesion revascularizations in patients with EES (2.6% vs. 4.9%, p = 0.03). The patient-oriented composite endpoint was similar (16.4% vs. 17.1%, p = 0.75). Two-year rates of definite or probable stent thrombosis were 1.2% and 1.4%, respectively (p = 0.63). Very late definite or probable stent thrombosis occurred only in 2 patients in each study arm (0.3% vs. 0.3%, p = 1.00). CONCLUSIONS: After 2 years of follow-up and stringent discontinuation of DAPT beyond 12 months, Resolute ZES and Xience V EES showed similar results in terms of safety and efficacy for treating patients with a majority of complex lesions and off-label indications for drug-eluting stents. (The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twente [TWENTE]; NCT01066650).

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.

Comparison of frequency of periprocedural myocardial infarction in patients with and without diabetes mellitus to those with previously unknown but elevated glycated hemoglobin levels (from the TWENTE Trial).

In patients without a history of diabetes mellitus, increased levels of glycated hemoglobin (HbA1c) are associated with higher cardiovascular risk. The relation between undetected diabetes and clinical outcome after percutaneous coronary intervention is unknown. To investigate whether these patients may have an increased risk of periprocedural myocardial infarction (PMI), the most frequent adverse event after percutaneous coronary intervention, we assessed patients of the TWENTE trial (a randomized, controlled, second-generation drug-eluting stent trial) in whom HbA1c data were available. Patients were classified as known diabetics or patients without a history of diabetes who were subdivided into undetected diabetics (HbA1c ≥6.5%) and nondiabetics (HbA1c <6.5%). Systematic measurement of cardiac biomarkers and electrocardiographic assessment were performed. One-year clinical outcome was also compared. Of 626 patients, 44 (7%) were undetected diabetics, 181 (29%) were known diabetics, and 401 (64%) were nondiabetics. In undetected diabetics the PMI rate was higher than in nondiabetics (13.6% vs 3.7%, p = 0.01) and known diabetics (13.6% vs 6.1%, p = 0.11). Multivariate analysis adjusting for covariates confirmed a significantly higher PMI risk in undetected diabetics compared to nondiabetics (odds ratio 6.13, 95% confidence interval 2.07 to 18.13, p = 0.001) and known diabetics (odds ratio 3.73, 95% confidence interval 1.17 to 11.89, p = 0.03). After 1 year, target vessel MI rate was significantly higher in undetected diabetics (p = 0.02) than in nondiabetics, which was related mainly to differences in PMI. Target vessel failure was numerically larger in unknown diabetics than in nondiabetics, but this difference did not reach statistical significance (13.6% vs 8.0%, p = 0.25). In conclusion, undetected diabetics were shown to have an increased risk of PMI.

A randomized controlled trial in second-generation zotarolimus-eluting Resolute stents versus everolimus-eluting Xience V stents in real-world patients: the TWENTE trial.

OBJECTIVES: The aim of this study was to compare the safety and efficacy of Resolute zotarolimus-eluting stents (ZES) (Medtronic Cardiovascular, Santa Rosa, California) with Xience V everolimus-eluting stents (EES) (Abbott Vascular Devices, Santa Clara, California) at 1-year follow-up. BACKGROUND: Only 1 randomized trial previously compared these stents. METHODS: This investigator-initiated, patient-blinded, randomized noninferiority study had limited exclusion criteria (acute ST-segment elevation myocardial infarctions not eligible). Patients (n = 1,391; 81.4% of eligible population) were randomly assigned to ZES (n = 697) or EES (n = 694). Liberal use of stent post-dilation was encouraged. Cardiac biomarkers were systematically assessed. The primary endpoint was target vessel failure (TVF), a composite of cardiac death, myocardial infarction not clearly attributable to non-target vessels, and clinically indicated target-vessel revascularization. An external independent research organization performed clinical event adjudication (100% follow-up data available). Analysis was by intention-to-treat. RESULTS: Acute coronary syndromes were present in 52% and "off-label" feature in 77% of patients. Of the lesions, 70% were type B2/C; the post-dilation rate was very high (82%). In ZES and EES, TVF occurred in 8.2% and 8.1%, respectively (absolute risk-difference 0.1%; 95% confidence interval: -2.8% to 3.0%, p(noninferiority) = 0.001). There was no significant between-group difference in TVF components. The definite-or-probable stent thrombosis rates were relatively low and similar for ZES and EES (0.9% and 1.2%, respectively, p = 0.59). Definite stent thrombosis rates were also low (0.58% and 0%, respectively, p = 0.12). In EES, probable stent thrombosis beyond day 8 was observed only in patients not adhering to dual antiplatelet therapy. CONCLUSIONS: Resolute ZES were noninferior to Xience V EES in treating "real-world" patients with a vast majority of complex lesions and "off-label" indications for drug-eluting stents, which were implanted with liberal use of post-dilation. (The Real-World Endeavor Resolute Versus XIENCE V Drug-Eluting SteNt Study: Head-to-head Comparison of Clinical Outcome After Implantation of Second Generation Drug-eluting Stents in a Real World Scenario; NCT01066650).