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Coronary Artery Disease: HELP
Articles by Ewout W. Steyerberg
Based on 29 articles published since 2010
(Why 29 articles?)
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Between 2010 and 2020, Ewout Steyerberg wrote the following 29 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. 2017

Costa, Francesco / van Klaveren, David / James, Stefan / Heg, Dik / Räber, Lorenz / Feres, Fausto / Pilgrim, Thomas / Hong, Myeong-Ki / Kim, Hyo-Soo / Colombo, Antonio / Steg, Philippe Gabriel / Zanchin, Thomas / Palmerini, Tullio / Wallentin, Lars / Bhatt, Deepak L / Stone, Gregg W / Windecker, Stephan / Steyerberg, Ewout W / Valgimigli, Marco / Anonymous3640899. ·Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland; Erasmus University Medical Center, Rotterdam, Netherlands; Department of Clinical and Experimental Medicine, Policlinic "G Martino", University of Messina, Messina, Italy. · Erasmus University Medical Center, Rotterdam, Netherlands; Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA. · Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. · Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. · Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland. · Istituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil. · Severance Cardiovascular Hospital, Yonsei University College of Medicine and Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. · Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. · EMO-GVM Centro Cuore Columbus, Milan, Italy; Interventional Cardiology Department, San Raffaele Scientific Institute, Milan, Italy. · Department of Cardiology, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat Hospital, Paris, France. · Dipartimento Cardio-Toraco-Vascolare, University of Bologna, Bologna, Italy. · Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA, USA. · Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, USA. · Erasmus University Medical Center, Rotterdam, Netherlands. · Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland; Erasmus University Medical Center, Rotterdam, Netherlands. Electronic address: marco.valgimigli@insel.ch. ·Lancet · Pubmed #28290994.

ABSTRACT: BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y METHODS: A total of 14 963 patients treated with DAPT after coronary stenting-largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation-were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12-24 months) or short (3-6 months) treatment in relation to baseline bleeding risk. FINDINGS: The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61-0·85) in the derivation cohort, and 0·70 (0·65-0·74) in the PLATO trial validation cohort and 0·66 (0·61-0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (p INTERPRETATION: The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration. FUNDING: None.

2 Review Systematic review of guidelines on imaging of asymptomatic coronary artery disease. 2011

Ferket, Bart S / Genders, Tessa S S / Colkesen, Ersen B / Visser, Jacob J / Spronk, Sandra / Steyerberg, Ewout W / Hunink, M G Myriam. ·Department of Radiology, Erasmus University Medical Center, Dr. Molewaterplein 40, Rotterdam, the Netherlands. ·J Am Coll Cardiol · Pubmed #21474039.

ABSTRACT: OBJECTIVES: The purpose of this study was to critically appraise guidelines on imaging of asymptomatic coronary artery disease (CAD). BACKGROUND: Various imaging tests exist to detect CAD in asymptomatic persons. Because randomized controlled trials are lacking, guidelines that address the use of CAD imaging tests may disagree. METHODS: Guidelines in English published between January 1, 2003, and February 26, 2010, were retrieved using MEDLINE, Cumulative Index to Nursing and Allied Health Literature, the National Guideline Clearinghouse, the National Library for Health, the Canadian Medication Association Infobase, and the Guidelines International Network International Guideline Library. Guidelines developed by national and international medical societies from Western countries, containing recommendations on imaging of asymptomatic CAD were included. Rigor of development was scored by 2 independent reviewers using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. One reviewer performed full extraction of recommendations, which was checked by a second reviewer. RESULTS: Of 2,415 titles identified, 14 guidelines met our inclusion criteria. Eleven of 14 guidelines reported relationship with industry. The AGREE scores varied across guidelines from 21% to 93%. Two guidelines considered cost effectiveness. Eight guidelines recommended against or found insufficient evidence for testing of asymptomatic CAD. The other 6 guidelines recommended imaging patients at intermediate or high CAD risk based on the Framingham risk score, and 5 considered computed tomography calcium scoring useful for this purpose. CONCLUSIONS: Guidelines on risk assessment by imaging of asymptomatic CAD contain conflicting recommendations. More research, including randomized controlled trials, evaluating the impact of imaging on clinical outcomes and costs is needed.

3 Clinical Trial Predictive Performance of SYNTAX Score II in Patients With Left Main and Multivessel Coronary Artery Disease-analysis of CREDO-Kyoto registry. 2014

Campos, Carlos M / van Klaveren, David / Iqbal, Javaid / Onuma, Yoshinobu / Zhang, Yao-Jun / Garcia-Garcia, Hector M / Morel, Marie-Angele / Farooq, Vasim / Shiomi, Hiroki / Furukawa, Yutaka / Nakagawa, Yoshihisa / Kadota, Kazushige / Lemos, Pedro A / Kimura, Takeshi / Steyerberg, Ewout W / Serruys, Patrick W. ·Department of Interventional Cardiology, Erasmus Medical Centre-University Medical Centre Rotterdam. ·Circ J · Pubmed #24998278.

ABSTRACT: BACKGROUND: SYNTAX score II (SSII) provides individualized estimates of 4-year mortality after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in order to facilitate decision-making between these revascularization methods. The purpose of the present study was to assess SSII in a real-world multicenter registry with distinct regional and epidemiological characteristics. METHODS AND RESULTS: Long-term mortality was analyzed in 3,896 patients undergoing PCI (n=2,190) or CABG (n=1,796) from the Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) PCI/CABG registry cohort-2. SSII discriminated well in both CABG and PCI patient groups (concordance index [c-index], 0.70; 95% CI: 0.68-0.72; and 0.75, 95% CI: 0.72-0.78) surpassing anatomical SYNTAX score (SS; c-index, 0.50; 95% CI: 0.47-0.53; and 0.59, 95% CI: 0.57-0.61). SSII had the best discriminative ability to separate low-, medium- and high-risk tertiles, and calibration plots showed good predictive performance for CABG and PCI groups. Use of anatomical SS as a reference improved the overall reclassification provided by SSII, with a net reclassification index of 0.5 (P<0.01). CONCLUSIONS: SSII has robust prognostic accuracy, both in CABG and in PCI patient groups and, compared with the anatomical SS alone, was more accurate in stratifying patients for late mortality in a real-world complex coronary artery disease Eastern population.

4 Article An ordinal prediction model of the diagnosis of non-obstructive coronary artery and multi-vessel disease in the CARDIIGAN cohort. 2018

Edlinger, Michael / Dörler, Jakob / Ulmer, Hanno / Wanitschek, Maria / Steyerberg, Ewout W / Alber, Hannes F / Van Calster, Ben. ·Department of Medical Statistics, Informatics, and Health Economics, Medical University Innsbruck, Austria. · University Clinic of Internal Medicine III - Cardiology and Angiology, Medical University Innsbruck, Austria. · Department of Public Health, Erasmus University Medical Centre, Rotterdam, The Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Centre, The Netherlands. · Department of Cardiology and Karl Landsteiner Institute for Interdisciplinary Science, Rehabilitation Centre Münster in Tyrol, Austria; Department of Internal Medicine and Cardiology, Klinikum Klagenfurt, Austria. · Department of Biomedical Data Sciences, Leiden University Medical Centre, The Netherlands; Department of Development and Regeneration, KU, Leuven, Belgium. Electronic address: ben.vancalster@kuleuven.be. ·Int J Cardiol · Pubmed #29853277.

ABSTRACT: -- No abstract --

5 Article The proposed 'concordance-statistic for benefit' provided a useful metric when modeling heterogeneous treatment effects. 2018

van Klaveren, David / Steyerberg, Ewout W / Serruys, Patrick W / Kent, David M. ·Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, 800 Washington St, Boston, MA 02111, USA; Department of Medical Statistics, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands. Electronic address: d.van_klaveren@lumc.nl. · Department of Medical Statistics, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands; Department of Public Health, Erasmus University Medical Center, 's-Gravendijkwal 230, Rotterdam 3015 CE, The Netherlands. · National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LR, United Kingdom. · Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, 800 Washington St, Boston, MA 02111, USA. ·J Clin Epidemiol · Pubmed #29132832.

ABSTRACT: OBJECTIVES: Clinical prediction models that support treatment decisions are usually evaluated for their ability to predict the risk of an outcome rather than treatment benefit-the difference between outcome risk with vs. without therapy. We aimed to define performance metrics for a model's ability to predict treatment benefit. STUDY DESIGN AND SETTING: We analyzed data of the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial and of three recombinant tissue plasminogen activator trials. We assessed alternative prediction models with a conventional risk concordance-statistic (c-statistic) and a novel c-statistic for benefit. We defined observed treatment benefit by the outcomes in pairs of patients matched on predicted benefit but discordant for treatment assignment. The 'c-for-benefit' represents the probability that from two randomly chosen matched patient pairs with unequal observed benefit, the pair with greater observed benefit also has a higher predicted benefit. RESULTS: Compared to a model without treatment interactions, the SYNTAX score II had improved ability to discriminate treatment benefit (c-for-benefit 0.590 vs. 0.552), despite having similar risk discrimination (c-statistic 0.725 vs. 0.719). However, for the simplified stroke-thrombolytic predictive instrument (TPI) vs. the original stroke-TPI, the c-for-benefit (0.584 vs. 0.578) was similar. CONCLUSION: The proposed methodology has the potential to measure a model's ability to predict treatment benefit not captured with conventional performance metrics.

6 Article The External Validity of Prediction Models for the Diagnosis of Obstructive Coronary Artery Disease in Patients With Stable Chest Pain: Insights From the PROMISE Trial. 2018

Genders, Tessa S S / Coles, Adrian / Hoffmann, Udo / Patel, Manesh R / Mark, Daniel B / Lee, Kerry L / Steyerberg, Ewout W / Hunink, M G Myriam / Douglas, Pamela S / Anonymous1370910. ·Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. · Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands. · Department of Epidemiology and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts. · Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. Electronic address: pamela.douglas@duke.edu. ·JACC Cardiovasc Imaging · Pubmed #28624401.

ABSTRACT: OBJECTIVES: This study sought to externally validate prediction models for the presence of obstructive coronary artery disease (CAD). BACKGROUND: A better assessment of the probability of CAD may improve the identification of patients who benefit from noninvasive testing. METHODS: Stable chest pain patients from the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial with computed tomography angiography (CTA) or invasive coronary angiography (ICA) were included. The authors assumed that patients with CTA showing 0% stenosis and a coronary artery calcium (CAC) score of 0 were free of obstructive CAD (≥50% stenosis) on ICA, and they multiply imputed missing ICA results based on clinical variables and CTA results. Predicted CAD probabilities were calculated using published coefficients for 3 models: basic model (age, sex, chest pain type), clinical model (basic model + diabetes, hypertension, dyslipidemia, and smoking), and clinical + CAC score model. The authors assessed discrimination and calibration, and compared published effects with observed predictor effects. RESULTS: In 3,468 patients (1,805 women; mean 60 years of age; 779 [23%] with obstructive CAD on CTA), the models demonstrated moderate-good discrimination, with C-statistics of 0.69 (95% confidence interval [CI]: 0.67 to 0.72), 0.72 (95% CI: 0.69 to 0.74), and 0.86 (95% CI: 0.85 to 0.88) for the basic, clinical, and clinical + CAC score models, respectively. Calibration was satisfactory although typical chest pain and diabetes were less predictive and CAC score was more predictive than was suggested by the models. Among the 31% of patients for whom the clinical model predicted a low (≤10%) probability of CAD, actual prevalence was 7%; among the 48% for whom the clinical + CAC score model predicted a low probability the observed prevalence was 2%. In 2 sensitivity analyses excluding imputed data, similar results were obtained using CTA as the outcome, whereas in those who underwent ICA the models significantly underestimated CAD probability. CONCLUSIONS: Existing clinical prediction models can identify patients with a low probability of obstructive CAD. Obstructive CAD on ICA was imputed for 61% of patients; hence, further validation is necessary.

7 Article Geographical Difference of the Interaction of Sex With Treatment Strategy in Patients With Multivessel Disease and Left Main Disease: A Meta-Analysis From SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and BEST (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) Randomized Controlled Trials. 2017

Sotomi, Yohei / Onuma, Yoshinobu / Cavalcante, Rafael / Ahn, Jung-Min / Lee, Cheol Whan / van Klaveren, David / de Winter, Robbert J / Wykrzykowska, Joanna J / Farooq, Vasim / Morice, Marie-Claude / Steyerberg, Ewout W / Park, Seung-Jung / Serruys, Patrick W. ·From the Academic Medical Center, University of Amsterdam, the Netherlands (Y.S., R.J.d.W., J.J.W.) · ThoraxCenter, Erasmus Medical Center, Rotterdam, the Netherlands (Y.O., R.C.) · Heart Institute, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea (J.-M.A., C.W.L., S.-J.P.) · Department of Public Health, Erasmus Medical Centre, Rotterdam, the Netherlands (D.v.K., E.W.S.) · Institute of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of Manchester and Manchester Heart Centre, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Trust, United Kingdom (V.F.) · Institut Cardiovasculaire Paris Sud, Générale de Santé, Hôpital Privé Jacques Cartier, Massy, France (M.-C.M.) · and International Centre for Circulatory Health, NHLI, Imperial College London, United Kingdom (P.W.S.). ·Circ Cardiovasc Interv · Pubmed #28495897.

ABSTRACT: BACKGROUND: The impact of sex on clinical outcomes of percutaneous coronary intervention and coronary artery bypass graft for patients with multivessel coronary disease and unprotected left main disease could be dissimilar between Western and Asian populations. METHODS AND RESULTS: To assess clinical outcomes after percutaneous coronary intervention or coronary artery bypass graft in women and men with multivessel coronary disease and unprotected left main disease, a pooled analysis (n=3280) was performed using the patient-level data from 3 large randomized trials: SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and BEST (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) trials. The primary end point was all-cause death. Of 3280 patients, 794 patients (24.2%) were women. The median follow-up period was 1806 days (1611-1837 days). In women, a high heterogeneity of the treatment effect among the 3 trials was found for all-cause death ( CONCLUSIONS: The present meta-analysis suggested the presence of the heterogeneous sex-treatment interaction across Asian and Western trials. Considering the ongoing globalization of our medical practice, the heterogeneity of the sex-treatment interaction needs to be well recognized and taken into account during the decision making of the treatment strategy. CLINICAL TRIAL REGISTRATIONS: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00114972, NCT00997828, NCT00422968.

8 Article External validation and extension of a diagnostic model for obstructive coronary artery disease: a cross-sectional predictive evaluation in 4888 patients of the Austrian Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort. 2017

Edlinger, Michael / Wanitschek, Maria / Dörler, Jakob / Ulmer, Hanno / Alber, Hannes F / Steyerberg, Ewout W. ·Department of Medical Statistics, Informatics, and Health Economics, Medical University Innsbruck, Innsbruck, Austria. · University Clinic of Internal Medicine III-Cardiology and Angiology, Medical University Innsbruck, Innsbruck, Austria. · Department of Cardiology, Karl Landsteiner Institute for Interdisciplinary Science, Rehabilitation Centre Münster in Tyrol, Münster, Austria. · Department of Public Health, Erasmus University Medical Centre, Rotterdam, The Netherlands. ·BMJ Open · Pubmed #28389492.

ABSTRACT: OBJECTIVE: To externally validate and extend a recently proposed prediction model to diagnose obstructive coronary artery disease (CAD), with the ultimate aim to better select patients for coronary angiography. DESIGN: Analysis of individual baseline data of a prospective cardiology cohort. SETTING: Single-centre secondary and tertiary cardiology clinic. PARTICIPANTS: 4888 patients with suspected CAD, without known previous CAD or other heart diseases, who underwent an elective coronary angiography between 2004 and 2008 as part of the prospective Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort. Relevant data were recorded as in routine clinical practice. MAIN OUTCOME MEASURES: The probability of obstructive CAD, defined as a stenosis of minimally 50% diameter in at least one of the main coronary arteries, estimated with the predictors age, sex, type of chest pain, diabetes status, hypertension, dyslipidaemia, smoking status and laboratory data. Missing predictor data were multiply imputed. Performance of the suggested models was evaluated according to discrimination (area under the receiver operating characteristic curve, depicted by the c statistic) and calibration. Logistic regression modelling was applied for model updating. RESULTS: Among the 4888 participants (38% women and 62% men), 2127 (44%) had an obstructive CAD. The previously proposed model had a c statistic of 0.69 (95% CI 0.67 to 0.70), which was lower than the expected c statistic while correcting for case mix (c=0.80). Regarding calibration, there was overprediction of risk for high-risk patients. All logistic regression coefficients were smaller than expected, especially for the predictor 'chest pain'. Extension of the model with high-density lipoprotein and low-density lipoprotein cholesterol, fibrinogen, and C reactive protein led to better discrimination (c=0.72, 95% CI 0.71 to 0.74, p<0.001 for improvement). CONCLUSIONS: The proposed prediction model has a moderate performance to diagnose obstructive CAD in an unselected patient group with suspected CAD referred for elective CA. A small, but significant improvement was attained by including easily available and measurable cardiovascular risk factors.

9 Article Individual Long-Term Mortality Prediction Following Either Coronary Stenting or Bypass Surgery in Patients With Multivessel and/or Unprotected Left Main Disease: An External Validation of the SYNTAX Score II Model in the 1,480 Patients of the BEST and PRECOMBAT Randomized Controlled Trials. 2016

Sotomi, Yohei / Cavalcante, Rafael / van Klaveren, David / Ahn, Jung-Min / Lee, Cheol Whan / de Winter, Robbert J / Wykrzykowska, Joanna J / Onuma, Yoshinobu / Steyerberg, Ewout W / Park, Seung-Jung / Serruys, Patrick W. ·Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. · ThoraxCenter, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands. · Heart Institute, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. · International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address: patrick.w.j.c.serruys@gmail.com. ·JACC Cardiovasc Interv · Pubmed #27491605.

ABSTRACT: OBJECTIVES: The study sought to validate the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score II mortality prediction model after percutaneous coronary intervention (PCI) or coronary artery bypass grafting in a large pooled population of patients with multivessel coronary disease (MVD) and/or unprotected left main disease (UPLMD) enrolled in the PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease) and BEST (Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) randomized controlled trials. BACKGROUND: For patients with MVD and/or UPLMD, the choice of the best revascularization strategy remains challenging. METHODS: Pooled individual patient-level data from PRECOMBAT and BEST were used to assess calibration and discrimination of the SYNTAX score II prediction model for all-cause mortality after PCI and coronary artery bypass grafting at 4-year follow-up. The study population comprised 1,480 patients (600 with UPLMD, 880 with MVD). RESULTS: The overall incidence of all-cause mortality was 6.1% after a median follow-up period of 4.9 years. Validation plots showed good model calibration overall and across treatment groups but tended to overestimate all-cause mortality in the highest risk quintiles of patients in the whole population and the PCI arm. The SYNTAX score II showed moderate discrimination ability for the whole population (C index = 0.685) but better for patients receiving PCI than CABG (C index = 0.718 vs. 0.662 in patients with UPLMD, C index = 0.700 vs. 0.661 in those with MVD). Observed all-cause mortality was higher when the treatment received was at variance with that recommended by the model and similar when it was concordant. CONCLUSIONS: The SYNTAX score II has good calibration but only moderate discrimination ability for long-term mortality prediction in this randomized population. This score provides an important tool to help guide the heart team's decision-making process regarding the selection of the best revascularization strategy for patients with MVD and/or UPLMD. (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease, NCT00422968; Bypass Surgery Versus Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease, NCT00997828).

10 Article Comparing the cost-effectiveness of four novel risk markers for screening asymptomatic individuals to prevent cardiovascular disease (CVD) in the US population. 2016

van Kempen, Bob J H / Ferket, Bart S / Steyerberg, Ewout W / Max, Wendy / Myriam Hunink, M G / Fleischmann, Kirsten E. ·Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; Department of Radiology, Erasmus MC, Rotterdam, The Netherlands. · Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, USA. · Department of Public Health, Erasmus MC, Rotterdam, The Netherlands. · Institute for Health & Aging and Department of Social and Behavioral Sciences, University of California, San Francisco, CA, USA. · Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; Department of Radiology, Erasmus MC, Rotterdam, The Netherlands; Department of Health Policy and Management, Harvard School of Public Health, Boston, MA, USA. Electronic address: m.hunink@erasmusmc.nl. · Department of Medicine, The University of California, San Francisco, CA, USA. ·Int J Cardiol · Pubmed #26547049.

ABSTRACT: BACKGROUND: High sensitivity CRP (hsCRP), coronary artery calcification on CT (CT calcium), carotid artery intima media thickness on ultrasound (cIMT) and ankle-brachial index (ABI) improve prediction of cardiovascular disease (CVD) risk, but the benefit of screening with these novel risk markers in the U.S. population is unclear. METHODS AND RESULTS: A microsimulation model evaluating lifelong cost-effectiveness for individuals aged 40-85 at intermediate risk of CVD, using 2003-2004 NHANES-III (N=3736), Framingham Heart Study, U.S. Vital Statistics, meta-analyses of independent predictive effects of the four novel risk markers and treatment effects was constructed. Using both an intention-to-treat (assumes adherence <100% and incorporates disutility from taking daily medications) and an as-treated (100% adherence and no disutility) analysis, quality adjusted life years (QALYs), lifetime costs (2014 US $), and incremental cost-effectiveness ratios (ICER in $/QALY gained) of screening with hsCRP, CT coronary calcium, cIMT and ABI were established compared with current practice, full adherence to current guidelines, and ubiquitous statin therapy. In the intention-to-treat analysis in men, screening with CT calcium was cost effective ($32,900/QALY) compared with current practice. In women, screening with hsCRP was cost effective ($32,467/QALY). In the as-treated analysis, statin therapy was both more effective and less costly than all other strategies for both men and women. CONCLUSIONS: When a substantial disutility from taking daily medication is assumed, screening men with CT coronary calcium is likely to be cost-effective whereas screening with hsCRP has value in women. The individual perceived disutility for taking daily medication should play a key role in the decision.

11 Article Cost-effectiveness of percutaneous coronary intervention versus bypass surgery from a Dutch perspective. 2015

Osnabrugge, Ruben L / Magnuson, Elizabeth A / Serruys, Patrick W / Campos, Carlos M / Wang, Kaijun / van Klaveren, David / Farooq, Vasim / Abdallah, Mouin S / Li, Haiyan / Vilain, Katherine A / Steyerberg, Ewout W / Morice, Marie-Claude / Dawkins, Keith D / Mohr, Friedrich W / Kappetein, A Pieter / Cohen, David J / Anonymous3300848. ·Department of Cardiovascular Research, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri, USA Department of Cardio-Thoracic Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands. · Department of Cardiovascular Research, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri, USA. · Department of Cardiology, Erasmus University Medical Centre, Rotterdam, The Netherlands. · Department of Cardiology, Erasmus University Medical Centre, Rotterdam, The Netherlands Heart Institute (InCor), University of São Paulo Medical School, Sao Paulo, Brazil. · Department of Public Health, Erasmus University Medical Centre, Rotterdam, The Netherlands. · Department of Interventional Cardiology, Institut Jacques Cartier, Massy, France. · Boston Scientific Corporation, Natick, Massachusetts, USA. · Department of Cardiac Surgery, Herzzentrum Universität Leipzig, Leipzig, Germany. · Department of Cardio-Thoracic Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands. ·Heart · Pubmed #26552756.

ABSTRACT: AIMS: Recent cost-effectiveness analyses of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) have been limited by a short time horizon or were restricted to the US healthcare perspective. We, therefore, used individual patient-level data from the SYNTAX trial to evaluate the cost-effectiveness of PCI versus CABG from a European (Dutch) perspective. METHODS AND RESULTS: Between 2005 and 2007, 1800 patients with three-vessel or left main coronary artery disease were randomised to either CABG (n=897) or PCI with drug-eluting stents (DES; n=903). Costs were estimated for all patients based on observed healthcare resource usage over 5 years of follow-up. Health state utilities were evaluated with the EuroQOL questionnaire. A patient-level microsimulation model based on Dutch life-tables was used to extrapolate the 5-year in-trial data to a lifetime horizon. Although initial procedural costs were lower for CABG, total initial hospitalisation costs per patient were higher (€17 506 vs €14 037, p<0.001). PCI was more costly during the next 5 years of follow-up, due to more frequent hospitalisations, repeat revascularisation procedures and higher medication costs. Nevertheless, total 5-year costs remained €2465/patient higher with CABG. When the in-trial results were extrapolated to a lifetime horizon, CABG was projected to be economically attractive relative to DES-PCI, with gains in both life expectancy and quality-adjusted life expectancy. The incremental cost-effectiveness ratio (ICER) (€5390/quality-adjusted life year (QALY) gained) was favourable and remained <€80 000/QALY in >90% of the bootstrap replicates. Outcomes were similar when incorporating the prognostic impact of non-fatal myocardial infarction and stroke, as well as across a broad range of assumptions regarding the effect of CABG on post-trial survival and costs. However, DES-PCI was economically dominant compared with CABG in patients with a SYNTAX Score ≤22 or in those with left main disease. In patients for whom the SYNTAX Score II favoured PCI based on lower predicted 4-year mortality, PCI was also economically dominant, whereas in those patients for whom the SYNTAX Score II favoured surgery, CABG was highly economically attractive (ICER range, €2967 to €3737/QALY gained). CONCLUSIONS: For the broad population with three-vessel or left main disease who are candidates for either CABG or PCI, we found that CABG is a clinically and economically attractive revascularisation strategy compared with DES-PCI from a Dutch healthcare perspective. The cost-effectiveness of CABG versus PCI differed according to several anatomic factors, however. The newly developed SYNTAX Score II provides enhanced prognostic discrimination in this population, and may be a useful tool to guide resource allocation as well. TRIAL REGISTRATION NUMBER: Clinical trial unique identifier: NCT00114972 (http://www.clinical-trials.gov).

12 Article Optimal medical therapy improves clinical outcomes in patients undergoing revascularization with percutaneous coronary intervention or coronary artery bypass grafting: insights from the Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) trial at the 5-year follow-up. 2015

Iqbal, Javaid / Zhang, Yao-Jun / Holmes, David R / Morice, Marie-Claude / Mack, Michael J / Kappetein, Arie Pieter / Feldman, Ted / Stahle, Elizabeth / Escaned, Javier / Banning, Adrian P / Gunn, Julian P / Colombo, Antonio / Steyerberg, Ewout W / Mohr, Friedrich W / Serruys, Patrick W. ·From the Thoraxcenter (J.I., Y.-J.Z., A.P.K., P.W.S.) and Department of Public Health (E.W.S.), Erasmus Medical Centre, Rotterdam, The Netherlands · University of Sheffield, UK (J.I., J.P.G.) · Mayo Clinic, Rochester, MN (D.R.H.) · ICPS, Hopital privé Jacques Cartier, Générale de Santé Massy, France (M.-C.M.) · The Heart Hospital, Dallas, TX (M.J.M.) · Evanston Hospital, IL (T.F.) · University Hospital Uppsala, Sweden (E.S.) · Hospital Clínico San Carlos, Madrid, Spain (J.E.) · Oxford University Hospitals, UK (A.P.B.) · San Raffaele Scientific Institute, Milan, Italy (A.C.) · Herzzentrum Universität Leipzig, Germany (F.W.M.) · and International Centre for Circulatory Health, Imperial College London, UK (P.W.S.). ·Circulation · Pubmed #25847979.

ABSTRACT: BACKGROUND: There is a paucity of data on the use of optimal medical therapy (OMT) in patients with complex coronary artery disease undergoing revascularization with percutaneous coronary intervention or coronary artery bypass grafting (CABG) and its long-term prognostic significance. METHODS AND RESULTS: The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial is a multicenter, randomized, clinical trial of patients (n=1800) with complex coronary disease randomized to revascularization with percutaneous coronary intervention or CABG. Detailed drug history was collected for all patients at discharge and at the 1-month, 6-month, 1-year, 3-year, and 5-year follow-ups. OMT was defined as the combination of at least 1 antiplatelet drug, statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Five-year clinical outcomes were stratified by OMT and non-OMT. OMT was underused in patients treated with coronary revascularization, especially CABG. OMT was an independent predictor of survival. OMT was associated with a significant reduction in mortality (hazard ratio, 0.64; 95% confidence interval, 0.48-0.85; P=0.002) and composite end point of death/myocardial infarction/stroke (hazard ratio, 0.73; 95% confidence interval, 0.58-0.92; P=0.007) at the 5-year follow-up. The treatment effect with OMT (36% relative reduction in mortality over 5 years) was greater than the treatment effect of revascularization strategy (26% relative reduction in mortality with CABG versus percutaneous coronary intervention over 5 years). On stratified analysis, all the components of OMT were important for reducing adverse outcomes regardless of revascularization strategy. CONCLUSIONS: The use of OMT remains low in patients with complex coronary disease requiring coronary intervention with percutaneous coronary intervention and even lower in patients treated with CABG. Lack of OMT is associated with adverse clinical outcomes. Targeted strategies to improve OMT use in postrevascularization patients are warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00114972.

13 Article Validity of SYNTAX score II for risk stratification of percutaneous coronary interventions: A patient-level pooled analysis of 5,433 patients enrolled in contemporary coronary stent trials. 2015

Campos, Carlos M / Garcia-Garcia, Hector M / van Klaveren, David / Ishibashi, Yuki / Cho, Yun-Kyeong / Valgimigli, Marco / Räber, Lorenz / Jonker, Hans / Onuma, Yoshinobu / Farooq, Vasim / Garg, Scot / Windecker, Stephan / Morel, Marie-Angele / Steyerberg, Ewout W / Serruys, Patrick W. ·Department of Interventional Cardiology, Erasmus University Medical Centre, Thoraxcenter, Rotterdam, The Netherlands; Department of Interventional Cardiology Heart Institute (InCor), University of São Paulo Medical School, Sao Paulo, Brazil. · Department of Interventional Cardiology, Erasmus University Medical Centre, Thoraxcenter, Rotterdam, The Netherlands; Cardialysis, Rotterdam, The Netherlands. Electronic address: h.garciagarcia@erasmusmc.nl. · Department of Public Health, Erasmus MC - University Medical Centre Rotterdam, Rotterdam, The Netherlands. · Department of Interventional Cardiology, Erasmus University Medical Centre, Thoraxcenter, Rotterdam, The Netherlands. · Department of Cardiology, Bern University Hospital, Bern, Switzerland. · Cardialysis, Rotterdam, The Netherlands. · Department of Cardiology, East Lancashire Hospitals NHS Trust, Blackburn, United Kingdom. · Department of Interventional Cardiology, Erasmus University Medical Centre, Thoraxcenter, Rotterdam, The Netherlands; International Centre for Circulatory Health, NHLI, Imperial College London, London, United Kingdom. ·Int J Cardiol · Pubmed #25828327.

ABSTRACT: OBJECTIVES: To assess the clinical profile and long-term mortality in SYNTAX score II based strata of patients who received percutaneous coronary interventions (PCI) in contemporary randomized trials. BACKGROUND: The SYNTAX score II was developed in the randomized, all-comers' SYNTAX trial population and is composed by 2 anatomical and 6 clinical variables. The interaction of these variables with the treatment provides individual long-term mortality predictions if a patient undergoes coronary artery bypass grafting (CABG) or PCI. METHODS: Patient-level (n=5433) data from 7 contemporary coronary drug-eluting stent (DES) trials were pooled. The mortality for CABG or PCI was estimated for every patient. The difference in mortality estimates for these two revascularization strategies was used to divide the patients into three groups of theoretical treatment recommendations: PCI, CABG or PCI/CABG (the latter means equipoise between CABG and PCI for long term mortality). RESULTS: The three groups had marked differences in their baseline characteristics. According to the predicted risk differences, 5115 patients could be treated either by PCI or CABG, 271 should be treated only by PCI and, rarely, CABG (n=47) was recommended. At 3-year follow-up, according to the SYNTAX score II recommendations, patients recommended for CABG had higher mortality compared to the PCI and PCI/CABG groups (17.4%; 6.1% and 5.3%, respectively; P<0.01). CONCLUSIONS: The SYNTAX score II demonstrated capability to help in stratifying PCI procedures.

14 Article Estimates of absolute treatment benefit for individual patients required careful modeling of statistical interactions. 2015

van Klaveren, David / Vergouwe, Yvonne / Farooq, Vasim / Serruys, Patrick W / Steyerberg, Ewout W. ·Department of Public Health, Erasmus MC: University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. Electronic address: d.vanklaveren.1@erasmusmc.nl. · Department of Public Health, Erasmus MC: University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. · Department of Interventional Cardiology, Thoraxcenter, Erasmus MC: University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands; Manchester Heart Centre, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Trust, Oxford Road, Manchester M13 9WL, United Kingdom. · Department of Interventional Cardiology, Thoraxcenter, Erasmus MC: University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. ·J Clin Epidemiol · Pubmed #25814403.

ABSTRACT: OBJECTIVES: We aimed to compare modeling approaches to estimate the individual survival benefit of treatment with either coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI) for patients with complex coronary artery disease. STUDY DESIGN AND SETTING: We estimated survival with Cox regression models that included the treatment variable (CABG/PCI) interacting with either an internally developed overall prognostic index (PI) or with individual prognostic factors. We analyzed data of patients who were randomized in the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery trial (1,800 patients, 178 deaths). RESULTS: A negligible interaction with the PI (P = 0.51) led to 4-year survival estimates in favor of CABG for all patients. In contrast, individual interactions indicated substantial relative treatment effect heterogeneity (overall interaction P = 0.004), and estimates of 4-year survival were numerically in favor of CABG for 1,275 of 1,800 patients (71%; 519 with 95% confidence). To test the more complex model with individual interactions, we first used penalized regression, resulting in smaller but largely consistent individual estimates of the survival difference between CABG and PCI. Second, strong treatment interactions were confirmed at external validation in 2,891 patients from a multinational registry. CONCLUSION: Modeling strategies that omit interactions may result in misleading estimates of absolute treatment benefit for individual patients with the potential hazard of suboptimal decision making.

15 Article Smoking is associated with adverse clinical outcomes in patients undergoing revascularization with PCI or CABG: the SYNTAX trial at 5-year follow-up. 2015

Zhang, Yao-Jun / Iqbal, Javaid / van Klaveren, David / Campos, Carlos M / Holmes, David R / Kappetein, Arie Pieter / Morice, Marie-Claude / Banning, Adrian P / Grech, Ever D / Bourantas, Christos V / Onuma, Yoshinobu / Garcia-Garcia, Hector M / Mack, Michael J / Colombo, Antonio / Mohr, Friedrich W / Steyerberg, Ewout W / Serruys, Patrick W. ·Thoraxcenter, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. · Sheffield Teaching Hospitals and the University of Sheffield, Sheffield, United Kingdom. · Department of Public Health, Erasmus Medical Centre, Rotterdam, the Netherlands. · Thoraxcenter, Erasmus Medical Centre, Rotterdam, the Netherlands. · Mayo Clinic, Rochester, Minnesota. · Institut Jacques Cartier, Massy, France. · Oxford University Hospitals, Oxford, United Kingdom. · The Heart Hospital, Plano, Texas. · San Raffaele Scientific Institute, Milan, Italy. · Herzzentrum Universität Leipzig, Leipzig, Germany. · Thoraxcenter, Erasmus Medical Centre, Rotterdam, the Netherlands; International Centre for Circulatory Health, Imperial College London, London, United Kingdom. Electronic address: patrick.w.j.c.serruys@gmail.com. ·J Am Coll Cardiol · Pubmed #25790882.

ABSTRACT: BACKGROUND: Cigarette smoking is a well-known risk factor for development of coronary artery disease (CAD). However, some studies have suggested a "smoker's paradox," meaning neutral or favorable outcomes in smokers who have developed CAD, especially myocardial infarction (MI). OBJECTIVES: The study aimed to examine the association of smoking status with clinical outcomes in the randomized controlled SYNTAX (SYNergy Between PCI With TAXUS and Cardiac Surgery) trial at 5-year follow-up. METHODS: Detailed smoking history was collected at baseline, 6-month, 1-year, 3-year, and 5-year follow-up. The composite endpoints included death/MI/stroke (primary endpoint) plus major adverse cardiac and cerebrovascular events (MACCE) (combination of death/MI/stroke and target lesion revascularization) according to patient smoking status. The comparison of 5-year clinical outcomes between the groups according to smoking status was performed with Cox regression using smoking status at baseline or smoking as a time-dependent covariate. RESULTS: A sizeable proportion (n = 322, 17.9%) of patients had changing smoking status during 5-year follow-up. One in 5 patients with complex CAD was smoking at baseline. However, 60% stopped after revascularization while others continued to smoke. Smokers had worse clinical outcomes due to a higher incidence of recurrent MI in both revascularization arms. Smoking was an independent predictor of the composite endpoint of death/MI/stroke (hazard ratio [HR]: 1.8; 95% confidence interval [CI]: 1.3 to 2.5; p = 0.001) and MACCE (HR: 1.4; 95% CI: 1.1 to 1.7; p = 0.02). CONCLUSIONS: Smoking is associated with poor clinical outcomes after revascularization in patients with complex CAD. This places further emphasis on efforts at smoking cessation to improve revascularization benefits. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972).

16 Article Long-term forecasting and comparison of mortality in the Evaluation of the Xience Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial: prospective validation of the SYNTAX Score II. 2015

Campos, Carlos M / van Klaveren, David / Farooq, Vasim / Simonton, Charles A / Kappetein, Arie-Pieter / Sabik, Joseph F / Steyerberg, Ewout W / Stone, Gregg W / Serruys, Patrick W / Anonymous4230817. ·Erasmus University Medical Center, s-Gravendijkwal 230, Rotterdam 3015, The Netherlands Heart Institute (InCor), University of São Paulo Medical School, Sao Paulo, Brazil. · Erasmus University Medical Center, s-Gravendijkwal 230, Rotterdam 3015, The Netherlands. · Manchester Heart Centre, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Trust, Manchester, UK. · Abbott Vascular, Santa Clara, CA, USA. · Department of Cardiothoracic Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, USA. · Columbia University Medical Center, New York, NY, USA Cardiovascular Research Foundation, New York, NY, USA. · Erasmus University Medical Center, s-Gravendijkwal 230, Rotterdam 3015, The Netherlands International Centre for Circulatory Health, NHLI, Imperial College London, London, UK patrick.w.j.c.serruys@gmail.com. ·Eur Heart J · Pubmed #25583761.

ABSTRACT: AIMS: To prospectively validate the SYNTAX Score II and forecast the outcomes of the randomized Evaluation of the Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) Trial. METHODS AND RESULTS: Evaluation of the Xience Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization is a prospective, randomized multicenter trial designed to establish the efficacy and safety of percutaneous coronary intervention (PCI) with the everolimus-eluting stent compared with coronary artery bypass graft (CABG) surgery in subjects with unprotected left-main coronary artery (ULMCA) disease and low-intermediate anatomical SYNTAX scores (<33). After completion of patient recruitment in EXCEL, the SYNTAX Score II was prospectively applied to predict 4-year mortality in the CABG and PCI arms. The 95% prediction intervals (PIs) for mortality were computed using simulation with bootstrap resampling (10 000 times). For the entire study cohort, the 4-year predicted mortalities were 8.5 and 10.5% in the PCI and CABG arms, respectively [odds ratios (OR) 0.79; 95% PI 0.43-1.50). In subjects with low (≤22) anatomical SYNTAX scores, the predicted OR was 0.69 (95% PI 0.34-1.45); in intermediate anatomical SYNTAX scores (23-32), the predicted OR was 0.93 (95% PI 0.53-1.62). Based on 4-year mortality predictions in EXCEL, clinical characteristics shifted long-term mortality predictions either in favour of PCI (older age, male gender and COPD) or CABG (younger age, lower creatinine clearance, female gender, reduced left ventricular ejection fraction). CONCLUSION: The SYNTAX Score II indicates at least an equipoise for long-term mortality between CABG and PCI in subjects with ULMCA disease up to an intermediate anatomical complexity. Both anatomical and clinical characteristics had a clear impact on long-term mortality predictions and decision making between CABG and PCI.

17 Article Sex differences in lifetime risk and first manifestation of cardiovascular disease: prospective population based cohort study. 2014

Leening, Maarten J G / Ferket, Bart S / Steyerberg, Ewout W / Kavousi, Maryam / Deckers, Jaap W / Nieboer, Daan / Heeringa, Jan / Portegies, Marileen L P / Hofman, Albert / Ikram, M Arfan / Hunink, M G Myriam / Franco, Oscar H / Stricker, Bruno H / Witteman, Jacqueline C M / Roos-Hesselink, Jolien W. ·Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Department of Cardiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Department of Epidemiology, Harvard School of Public Health, Boston, MA, US. · Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Department of Radiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Institute of Healthcare Delivery Science, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, US. · Department of Public Health, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands. · Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands. · Department of Cardiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands. · Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Department of Neurology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands. · Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Department of Epidemiology, Harvard School of Public Health, Boston, MA, US. · Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Department of Radiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Department of Neurology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands. · Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Department of Radiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Department of Health Policy and Management, Harvard School of Public Health, Boston, MA, US. · Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands Inspectorate for Health Care, The Hague, Netherlands b.stricker@erasmusmc.nl. ·BMJ · Pubmed #25403476.

ABSTRACT: OBJECTIVE: To evaluate differences in first manifestations of cardiovascular disease between men and women in a competing risks framework. DESIGN: Prospective population based cohort study. SETTING: People living in the community in Rotterdam, the Netherlands. PARTICIPANTS: 8419 participants (60.9% women) aged ≥ 55 and free from cardiovascular disease at baseline. MAIN OUTCOME MEASURES: First diagnosis of coronary heart disease (myocardial infarction, revascularisation, and coronary death), cerebrovascular disease (stroke, transient ischaemic attack, and carotid revascularisation), heart failure, or other cardiovascular death; or death from non-cardiovascular causes. Data were used to calculate lifetime risks of cardiovascular disease and its first incident manifestations adjusted for competing non-cardiovascular death. RESULTS: During follow-up of up to 20.1 years, 2888 participants developed cardiovascular disease (826 coronary heart disease, 1198 cerebrovascular disease, 762 heart failure, and 102 other cardiovascular death). At age 55, overall lifetime risks of cardiovascular disease were 67.1% (95% confidence interval 64.7% to 69.5%) for men and 66.4% (64.2% to 68.7%) for women. Lifetime risks of first incident manifestations of cardiovascular disease in men were 27.2% (24.1% to 30.3%) for coronary heart disease, 22.8% (20.4% to 25.1%) for cerebrovascular disease, 14.9% (13.3% to 16.6%) for heart failure, and 2.3% (1.6% to 2.9%) for other deaths from cardiovascular disease. For women the figures were 16.9% (13.5% to 20.4%), 29.8% (27.7% to 31.9%), 17.5% (15.9% to 19.2%), and 2.1% (1.6% to 2.7%), respectively. Differences in the number of events that developed over the lifespan in women compared with men (per 1000) were -7 for any cardiovascular disease, -102 for coronary heart disease, 70 for cerebrovascular disease, 26 for heart failure, and -1 for other cardiovascular death; all outcomes manifested at a higher age in women. Patterns were similar when analyses were restricted to hard atherosclerotic cardiovascular disease outcomes, but absolute risk differences between men and women were attenuated for both coronary heart disease and stroke. CONCLUSIONS: At age 55, though men and women have similar lifetime risks of cardiovascular disease, there are considerable differences in the first manifestation. Men are more likely to develop coronary heart disease as a first event, while women are more likely to have cerebrovascular disease or heart failure as their first event, although these manifestations appear most often at older ages.

18 Article Prognostic value of site SYNTAX score and rationale for combining anatomic and clinical factors in decision making: insights from the SYNTAX trial. 2014

Zhang, Yao-Jun / Iqbal, Javaid / Campos, Carlos M / Klaveren, David V / Bourantas, Christos V / Dawkins, Keith D / Banning, Adrian P / Escaned, Javier / de Vries, Ton / Morel, Marie-Angèle / Farooq, Vasim / Onuma, Yoshinobu / Garcia-Garcia, Hector M / Stone, Gregg W / Steyerberg, Ewout W / Mohr, Friedrich W / Serruys, Patrick W. ·Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; Nanjing First Hospital, Nanjing Medical University, Nanjing, China. · Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands. · Boston Scientific Corporation, Natick, Massachusetts. · Oxford University Hospitals, Oxford, United Kingdom. · Clinico San Carlos University Hospital, Madrid, Spain. · Cardialysis BV, Rotterdam, the Netherlands. · Columbia University Medical Center/New York-Presbyterian Hospital, Cardiovascular Research Foundation, New York, New York. · Herzzentrum Universität Leipzig, Leipzig, Germany. · Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; Imperial College London, London, United Kingdom. Electronic address: patrick.w.j.c.serruys@gmail.com. ·J Am Coll Cardiol · Pubmed #25082573.

ABSTRACT: BACKGROUND: The results of SYNTAX trial have been reported based on "corelab" calculated SS (cSS). It has been shown that reproducibility of SS is better among the core laboratory technicians than interventional cardiologists. Thus, the prognostic value and clinical implication of the "site" SYNTAX SS (sSS) remain unknown. OBJECTIVES: The study sought to evaluate the prognostic value and clinical implication of the sSS after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery in the randomized SYNTAX trial. METHODS: The sSS was calculated by the site investigators before randomization in the SYNTAX trial. New tertiles based on the sSS were defined with low (0 to 19), intermediate (20 to 27), and high (≥28) scores. The clinical endpoints were compared between PCI and CABG by Kaplan-Meier estimates, log-rank comparison, and Cox regression analyses using the new tertiles. The sSS-based SS II was calculated and its predictive performance was evaluated. RESULTS: The mean difference in cSS and sSS is 3.8 ± 11.2, with a mean absolute difference of 8.9 ± 7.8. In the overall cohort, using sSS there was a higher incidence of major adverse cardiac and cerebrovascular events (MACCE) at 5-year follow-up in the PCI group for low (31.9% vs. 24.5%; p = 0.054), intermediate (39.5% vs. 29.5%; p = 0.019), and high (43.0% vs. 31.4%; p = 0.003) tertiles, compared with the CABG group. Similarly, in the 3-vessel disease subgroup, 5-year MACCE rates were higher in PCI group in all tertiles. Conversely, in the left main subgroup, MACCE rates were similar for PCI and CABG groups in all tertiles. The sSS-based SS II (c-index: 0.736) had predictive performance similar to the cSS-based SS II (c-index: 0.744), with net reclassification index of -0.0062 (p = 0.79). CONCLUSIONS: Appropriate training and unbiased assessment are needed when using SS in clinical decision making. sSS and tertiles based on sSS showed poor discrimination among low, intermediate, and high-risk groups. However, combining clinical factors with sSS retained the predictive performance of SS II. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972).

19 Article Predicting 3-year mortality after percutaneous coronary intervention: updated logistic clinical SYNTAX score based on patient-level data from 7 contemporary stent trials. 2014

Iqbal, Javaid / Vergouwe, Yvonne / Bourantas, Christos V / van Klaveren, David / Zhang, Yao-Jun / Campos, Carlos M / García-García, Hector M / Morel, Marie-Angele / Valgimigli, Marco / Windecker, Stephan / Steyerberg, Ewout W / Serruys, Patrick W. ·Department of Interventional Cardiology, Thoraxcenter, Rotterdam, the Netherlands; Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom. · Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Interventional Cardiology, Thoraxcenter, Rotterdam, the Netherlands. · Cardialysis, Rotterdam, the Netherlands. · Cardiology Department, Bern University Hospital, Bern, Switzerland. · Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom. · Department of Interventional Cardiology, Thoraxcenter, Rotterdam, the Netherlands; Department of Cardiology, Imperial College London, London, United Kingdom. Electronic address: patrick.w.j.c.serruys@gmail.com. ·JACC Cardiovasc Interv · Pubmed #24852801.

ABSTRACT: OBJECTIVES: This study aimed to update the Logistic Clinical SYNTAX score to predict 3-year survival after percutaneous coronary intervention (PCI) and compare the performance with the SYNTAX score alone. BACKGROUND: The SYNTAX score is a well-established angiographic tool to predict long-term outcomes after PCI. The Logistic Clinical SYNTAX score, developed by combining clinical variables with the anatomic SYNTAX score, has been shown to perform better than the SYNTAX score alone in predicting 1-year outcomes after PCI. However, the ability of this score to predict long-term survival is unknown. METHODS: Patient-level data (N = 6,304, 399 deaths within 3 years) from 7 contemporary PCI trials were analyzed. We revised the overall risk and the predictor effects in the core model (SYNTAX score, age, creatinine clearance, and left ventricular ejection fraction) using Cox regression analysis to predict mortality at 3 years. We also updated the extended model by combining the core model with additional independent predictors of 3-year mortality (i.e., diabetes mellitus, peripheral vascular disease, and body mass index). RESULTS: The revised Logistic Clinical SYNTAX models showed better discriminative ability than the anatomic SYNTAX score for the prediction of 3-year mortality after PCI (c-index: SYNTAX score, 0.61; core model, 0.71; and extended model, 0.73 in a cross-validation procedure). The extended model in particular performed better in differentiating low- and intermediate-risk groups. CONCLUSIONS: Risk scores combining clinical characteristics with the anatomic SYNTAX score substantially better predict 3-year mortality than the SYNTAX score alone and should be used for long-term risk stratification of patients undergoing PCI.

20 Article Tools & Techniques: Analysis of clustered data in interventional cardiology: current practice and methodological advice. 2013

Lingsma, Hester / Nauta, Sjoerd / van Leeuwen, Nikki / Borsboom, Gerard / Bruining, Nico / Steyerberg, Ewout. ·Department of Public Health, Erasmus MC, Rotterdam, The Netherlands. h.lingsma@erasmusmc.nl ·EuroIntervention · Pubmed #23685305.

ABSTRACT: -- No abstract --

21 Article Development and validation of a cardiovascular risk assessment model in patients with established coronary artery disease. 2013

Battes, Linda / Barendse, Rogier / Steyerberg, Ewout W / Simoons, Maarten L / Deckers, Jaap W / Nieboer, Daan / Bertrand, Michel / Ferrari, Roberto / Remme, Willem J / Fox, Kim / Takkenberg, Johanna J M / Boersma, Eric / Kardys, Isabella. ·Clinical Epidemiology Unit, Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands. ·Am J Cardiol · Pubmed #23558041.

ABSTRACT: Appropriate risk stratification of patients with established, stable coronary artery disease could contribute to the prevention of recurrent cardiovascular events. The purpose of the present study was to develop and validate risk prediction models for various cardiovascular end points in the EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) database, consisting of 12,218 patients with established coronary artery disease, with a median follow-up of 4.1 years. Cox proportional hazards models were used for model development. The end points examined were cardiovascular mortality, noncardiovascular mortality, nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, resuscitated cardiac arrest, and combinations of these end points. The performance measures included Nagelkerke's R², time-dependent area under the receiver operating characteristic curves, and calibration plots. Backward selection resulted in a prediction model for cardiovascular mortality (464 events) containing age, current smoking, diabetes mellitus, total cholesterol, body mass index, previous myocardial infarction, history of congestive heart failure, peripheral vessel disease, previous revascularization, and previous stroke. The model performance was adequate for this end point, with a Nagelkerke R² of 12%, and an area under the receiver operating characteristic curve of 0.73. However, the performance of models constructed for nonfatal and combined end points was considerably worse, with an area under the receiver operating characteristic curve of about 0.6. In conclusion, in patients with established coronary artery disease, the risk of cardiovascular mortality during longer term follow-up can be adequately predicted using the clinical characteristics available at baseline. However, the prediction of nonfatal outcomes, both separately and combined with fatal outcomes, poses major challenges for clinicians and model developers.

22 Article Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients: development and validation of SYNTAX score II. 2013

Farooq, Vasim / van Klaveren, David / Steyerberg, Ewout W / Meliga, Emanuele / Vergouwe, Yvonne / Chieffo, Alaide / Kappetein, Arie Pieter / Colombo, Antonio / Holmes, David R / Mack, Michael / Feldman, Ted / Morice, Marie-Claude / Ståhle, Elisabeth / Onuma, Yoshinobu / Morel, Marie-angèle / Garcia-Garcia, Hector M / van Es, Gerrit Anne / Dawkins, Keith D / Mohr, Friedrich W / Serruys, Patrick W. ·Thoraxcenter, Erasmus University Medical Center, Rotterdam, Netherlands. ·Lancet · Pubmed #23439103.

ABSTRACT: BACKGROUND: The anatomical SYNTAX score is advocated in European and US guidelines as an instrument to help clinicians decide the optimum revascularisation method in patients with complex coronary artery disease. The absence of an individualised approach and of clinical variables to guide decision making between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are limitations of the SYNTAX score. SYNTAX score II aimed to overcome these limitations. METHODS: SYNTAX score II was developed by applying a Cox proportional hazards model to results of the randomised all comers SYNTAX trial (n=1800). Baseline features with strong associations to 4-year mortality in either the CABG or the PCI settings (interactions), or in both (predictive accuracy), were added to the anatomical SYNTAX score. Comparisons of 4-year mortality predictions between CABG and PCI were made for each patient. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. External validation was done in the multinational all comers DELTA registry (n=2891), a heterogeneous population that included patients with three-vessel disease (26%) or complex coronary artery disease (anatomical SYNTAX score ≥33, 30%) who underwent CABG or PCI. The SYNTAX trial is registered with ClinicalTrials.gov, number NCT00114972. FINDINGS: SYNTAX score II contained eight predictors: anatomical SYNTAX score, age, creatinine clearance, left ventricular ejection fraction (LVEF), presence of unprotected left main coronary artery (ULMCA) disease, peripheral vascular disease, female sex, and chronic obstructive pulmonary disease (COPD). SYNTAX score II significantly predicted a difference in 4-year mortality between patients undergoing CABG and those undergoing PCI (p(interaction) 0·0037). To achieve similar 4-year mortality after CABG or PCI, younger patients, women, and patients with reduced LVEF required lower anatomical SYNTAX scores, whereas older patients, patients with ULMCA disease, and those with COPD, required higher anatomical SYNTAX scores. Presence of diabetes was not important for decision making between CABG and PCI (p(interaction) 0·67). SYNTAX score II discriminated well in all patients who underwent CABG or PCI, with concordance indices for internal (SYNTAX trial) validation of 0·725 and for external (DELTA registry) validation of 0·716, which were substantially higher than for the anatomical SYNTAX score alone (concordance indices of 0·567 and 0·612, respectively). A nomogram was constructed that allowed for an accurate individualised prediction of 4-year mortality in patients proposing to undergo CABG or PCI. INTERPRETATION: Long-term (4-year) mortality in patients with complex coronary artery disease can be well predicted by a combination of anatomical and clinical factors in SYNTAX score II. SYNTAX score II can better guide decision making between CABG and PCI than the original anatomical SYNTAX score. FUNDING: Boston Scientific Corporation.

23 Article Microsimulation for clinical decision-making in individual patients with established coronary artery disease: a concept. 2013

Battes, Linda / Kardys, Isabella / Barendse, Rogier / Steyerberg, Ewout W / Amiri, Masoud / Eijkemans, Marinus J C / Deckers, Jaap W / Postmus, Douwe / Takkenberg, Johanna J M / Redekop, Ken / Boersma, Eric. ·Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands. l.battes@erasmusmc.nl ·Circ J · Pubmed #23196719.

ABSTRACT: BACKGROUND: In cardiovascular disease, numerous evidence-based prognostic models have been created, usually based on regression analyses of isolated patient datasets. They tend to focus on one outcome event, based on just one baseline evaluation of the patient, and fail to take the disease process in its dynamic nature into account. We present so-called microsimulation as an attractive alternative for clinical decision-making in individual patients. We aim to further familiarize clinicians with the concept of microsimulation and to inform them about the modeling process. METHODS AND RESULTS: We describe the modeling process, advantages and disadvantages of microsimulation. We illustrate the concept using a hypothetical 60-year-old patient, with several cardiac risk factors, who is hospitalized for myocardial infarction. By using microsimulation, we calculate this patient's probability of death. In our example, this particular patient's estimated life expectancy turns out to be 8.9 years. While calculating this life expectancy, we were able to account for multiple outcome events and changing patient characteristics. CONCLUSIONS: Microsimulation takes into account the dynamic nature of coronary artery disease by estimating most likely outcomes regarding a broad range of clinical events. Moreover, microsimulation can be used to evaluate treatment effects by estimating the event-free life expectancy with and without treatment. Hence, microsimulation has several advantages compared to modeling techniques such as regression. 

24 Article Incidence and multivariable correlates of long-term mortality in patients treated with surgical or percutaneous revascularization in the synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) trial. 2012

Farooq, Vasim / Serruys, Patrick W / Bourantas, Christos / Vranckx, Pascal / Diletti, Roberto / Garcia Garcia, Hector M / Holmes, David R / Kappetein, Arie-Pieter / Mack, Michael / Feldman, Ted / Morice, Marie Claude / Colombo, Antonio / Morel, Marie-angèle / de Vries, Ton / van Es, Gerrit Anne / Steyerberg, Ewout W / Dawkins, Keith D / Mohr, Friedrich W / James, Stefan / Ståhle, Elisabeth. ·Department of Interventional Cardiology, Erasmus University Medical Centre, Thoraxcenter, s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. ·Eur Heart J · Pubmed #23103663.

ABSTRACT: AIMS: The aim of this investigation was to determine the incidence and multivariable correlates of long-term (4-year) mortality in patients treated with surgical or percutaneous revascularization in the synergy between percutaneous coronary intervention (PCI) with TAXUS Express and Cardiac Surgery (SYNTAX) trial. METHODS AND RESULTS: A total of 1800 patients were randomized to undergo coronary artery bypass graft (CABG) surgery (n = 897) or PCI (n = 903). Prospectively collected baseline and peri- and post-procedural data were used to determine independent correlates of 4-year all-cause death in the CABG and the PCI arms (Cox proportional hazards model). Four-year mortality rates in the CABG and the PCI arms were 9.0% [74 deaths (12 in-hospital)] and 11.8% [104 deaths (16 in-hospital)], respectively (log-rank P-value = 0.063). Censored data comprised 78 patients (8.7%) in the CABG arm, and 24 patients (2.7%) in the PCI arm (log-rank P-value < 0.001). Within the CABG arm, the strongest independent correlates of 4-year mortality were lack of discharge aspirin [hazard ratio (HR) 3.56; 95% CI: 2.04, 6.21; P < 0.001], peripheral vascular disease (PVD) (HR: 2.65; 95% CI: 1.49, 4.72; P = 0.001), chronic obstructive pulmonary disease, age, and serum creatinine. Within the PCI arm, the strongest independent correlate of 4-year mortality was lack of post-procedural anti-platelet therapy (HR: 152.16; 95% CI: 53.57, 432.22; P < 0.001), with 10 reported early (within 45 days) in-hospital deaths secondary to multifactorial causes precluding administration of anti-platelet therapy. Other independent correlates of mortality in the PCI arm included amiodarone therapy on discharge, pre-procedural poor left ventricular ejection fraction, a 'history of gastrointestinal bleeding or peptic ulcer disease', PVD (HR: 2.13; 95% CI: 1.26, 3.60; P = 0.005), age, female gender (HR: 1.60; 95% CI: 1.01, 2.56; P = 0.048), and the SYNTAX score (Per increase in 10 points: HR: 1.25; 95% CI: 1.06, 1.47; P = 0.007). CONCLUSION: Independent correlates of 4-year mortality in the SYNTAX trial were multifactorial. Lack of discharge aspirin and lack of post-procedural anti-platelet therapy were the strongest independent correlates of mortality in the CABG and the PCI arms, respectively. Peripheral vascular disease is a common independent correlate of 4-year mortality and may be a marker of the severity of baseline coronary disease and risk of future native coronary disease (and extra-cardiac disease) progression.

25 Article Coronary calcification and the risk of heart failure in the elderly: the Rotterdam Study. 2012

Leening, Maarten J G / Elias-Smale, Suzette E / Kavousi, Maryam / Felix, Janine F / Deckers, Jaap W / Vliegenthart, Rozemarijn / Oudkerk, Matthijs / Hofman, Albert / Steyerberg, Ewout W / Stricker, Bruno H Ch / Witteman, Jacqueline C M. ·Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. ·JACC Cardiovasc Imaging · Pubmed #22974798.

ABSTRACT: OBJECTIVES: The purpose of this study was to determine the association of coronary artery calcification (CAC) with incident heart failure in the elderly and examine its independence of overt coronary heart disease (CHD). BACKGROUND: Heart failure is often observed as a first manifestation of coronary atherosclerosis rather than a sequela of overt CHD. Although numerous studies have shown that CAC, an established measure of coronary atherosclerosis, is a strong predictor of CHD, the association between CAC and future heart failure has not been studied prospectively. METHODS: In the Rotterdam Study, a population-based cohort, 1,897 asymptomatic participants (mean age, 69.9 years; 58% women) underwent CAC scoring and were followed for the occurrence of heart failure and CHD. RESULTS: During a median follow-up of 6.8 years, there were 78 cases of heart failure and 76 cases of nonfatal CHD. After adjustment for cardiovascular risk factors, increasing CAC scores were associated with heart failure (p for trend = 0.001), with a hazard ratio of 4.1 (95% confidence interval [CI]: 1.7 to 10.1) for CAC scores >400 compared with CAC scores of 0 to 10. After censoring participants for incident nonfatal CHD, increasing extent of CAC remained associated with heart failure (p for trend = 0.046), with a hazard ratio of 2.9 (95% CI: 1.1 to 7.4) for CAC scores >400. Moreover, adding CAC to cardiovascular risk factors resulted in an optimism-corrected increase in the c-statistic by 0.030 (95% CI: 0.001 to 0.050) to 0.734 (95% CI: 0.698 to 0.770) and substantially improved the risk classification of subjects (continuous net reclassification index = 34.0%). CONCLUSIONS: CAC has a clear association with the risk of heart failure, independent of overt CHD. Because heart failure is highly prevalent in the elderly, it might be worthwhile to include heart failure as an outcome in future risk assessment programs incorporating CAC.

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