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Coronary Artery Disease: HELP
Articles by Stefan K. James
Based on 45 articles published since 2008
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Between 2008 and 2019, S. James wrote the following 45 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Report of an ESC-EAPCI Task Force on the evaluation and use of bioresorbable scaffolds for percutaneous coronary intervention: executive summary. 2018

Byrne, Robert A / Stefanini, Giulio G / Capodanno, Davide / Onuma, Yoshinobu / Baumbach, Andreas / Escaned, Javier / Haude, Michael / James, Stefan / Joner, Michael / Jüni, Peter / Kastrati, Adnan / Oktay, Semih / Wijns, William / Serruys, Patrick W / Windecker, Stephan. ·Deutsches Herzzentrum München, Technische Universität München, Germany. ·EuroIntervention · Pubmed #28948934.

ABSTRACT: A previous Task Force of the European Society of Cardiology (ESC) and European Association of Percutaneous Cardiovascular Interventions (EAPCI) provided a report on recommendations for the non-clinical and clinical evaluation of coronary stents. Following dialogue with the European Commission, the Task Force was asked to prepare an additional report on the class of devices known as bioresorbable scaffolds (BRS). Five BRS have CE-mark approval for use in Europe. Only one device -the Absorb bioresorbable vascular scaffold- has published randomized clinical trial data and this data show inferior outcomes to conventional drug-eluting stents (DES) at 2-3 years. For this reason, at present BRS should not be preferred to conventional DES in clinical practice. The Task Force recommends that new BRS devices should undergo systematic non-clinical testing according to standardized criteria prior to evaluation in clinical studies. A clinical evaluation plan should include data from a medium sized, randomized trial against DES powered for a surrogate end point of clinical efficacy. Manufacturers of successful devices receive CE- mark approval for use and must have an approved plan for a large-scale randomized clinical trial with planned long-term follow-up.

2 Guideline 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. 2013

Anonymous3190768 / Montalescot, Gilles / Sechtem, Udo / Achenbach, Stephan / Andreotti, Felicita / Arden, Chris / Budaj, Andrzej / Bugiardini, Raffaele / Crea, Filippo / Cuisset, Thomas / Di Mario, Carlo / Ferreira, J Rafael / Gersh, Bernard J / Gitt, Anselm K / Hulot, Jean-Sebastien / Marx, Nikolaus / Opie, Lionel H / Pfisterer, Matthias / Prescott, Eva / Ruschitzka, Frank / Sabaté, Manel / Senior, Roxy / Taggart, David Paul / van der Wall, Ernst E / Vrints, Christiaan J M / Anonymous3200768 / Zamorano, Jose Luis / Achenbach, Stephan / Baumgartner, Helmut / Bax, Jeroen J / Bueno, Héctor / Dean, Veronica / Deaton, Christi / Erol, Cetin / Fagard, Robert / Ferrari, Roberto / Hasdai, David / Hoes, Arno W / Kirchhof, Paulus / Knuuti, Juhani / Kolh, Philippe / Lancellotti, Patrizio / Linhart, Ales / Nihoyannopoulos, Petros / Piepoli, Massimo F / Ponikowski, Piotr / Sirnes, Per Anton / Tamargo, Juan Luis / Tendera, Michal / Torbicki, Adam / Wijns, William / Windecker, Stephan / Anonymous3210768 / Knuuti, Juhani / Valgimigli, Marco / Bueno, Héctor / Claeys, Marc J / Donner-Banzhoff, Norbert / Erol, Cetin / Frank, Herbert / Funck-Brentano, Christian / Gaemperli, Oliver / Gonzalez-Juanatey, José R / Hamilos, Michalis / Hasdai, David / Husted, Steen / James, Stefan K / Kervinen, Kari / Kolh, Philippe / Kristensen, Steen Dalby / Lancellotti, Patrizio / Maggioni, Aldo Pietro / Piepoli, Massimo F / Pries, Axel R / Romeo, Francesco / Rydén, Lars / Simoons, Maarten L / Sirnes, Per Anton / Steg, Ph Gabriel / Timmis, Adam / Wijns, William / Windecker, Stephan / Yildirir, Aylin / Zamorano, Jose Luis. ·The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines. ·Eur Heart J · Pubmed #23996286.

ABSTRACT: -- No abstract --

3 Guideline Meeting report ESC forum on drug eluting stents, European Heart House, Nice, 27-28 September 2007. 2009

Daemen, Joost / Simoons, Maarten L / Wijns, William / Bagust, Adrian / Bos, Gert / Bowen, James M / Braunwald, Eugene / Camenzind, Edoardo / Chevaliers, Bernard / DiMario, Carlo / Fajadeto, Jean / Gitt, Anselm / Guagliumi, Giulio / Hillege, Hans L / James, Stefan / Jüni, Peter / Kastrati, Adnan / Kloth, Sabine / Kristensen, Steen D / Krucoff, Mitchell / Legrand, Victor / Pfisterer, Matthias / Rothman, Martin / Serruys, Patrick W / Silber, Sigmund / Steg, Philippe G / Tariah, Ibrahim / Wallentin, Lars / Windecker, Stephan W / Aimonetti, A / Allocco, D / Berenger, M / Boam, A / Calle, J P / Campo, G / Carlier, S / de Schepper, J / Di Bisceglie, G / Dobbels, H / Farb, A / Ghislain, J C / Hellbardt, S / ten Hoedt, R / Isaia, C / de Jong, P / Lekehal, M / LeNarz, L / Mhullain, F Ni / Nagai, H / Patteet, A / Paunovic, D / Potgieter, A / Purdy, I / Raveau-Landon, C / Ternstrom, S / Van Wuytswinkel, J / Waliszewski, M / Anonymous830624. ·Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands. ·EuroIntervention · Pubmed #19284063.

ABSTRACT: -- No abstract --

4 Review Culprit Vessel-Only Versus Multivessel Percutaneous Coronary Intervention in Patients With Cardiogenic Shock Complicating ST-Segment-Elevation Myocardial Infarction: A Collaborative Meta-Analysis. 2017

Kolte, Dhaval / Sardar, Partha / Khera, Sahil / Zeymer, Uwe / Thiele, Holger / Hochadel, Matthias / Radovanovic, Dragana / Erne, Paul / Hambraeus, Kristina / James, Stefan / Claessen, Bimmer E / Henriques, Jose P S / Mylotte, Darren / Garot, Philippe / Aronow, Wilbert S / Owan, Theophilus / Jain, Diwakar / Panza, Julio A / Frishman, William H / Fonarow, Gregg C / Bhatt, Deepak L / Aronow, Herbert D / Abbott, J Dawn. ·From the Department of Medicine, Division of Cardiology, Brown University, Providence, RI (D.K., H.D.A., J.D.A.) · Department of Medicine, Division of Cardiology, University of Utah, Salt Lake City (P.S., T.O.) · Department of Medicine, Division of Cardiology, New York Medical College at Westchester Medical Center, Valhalla (S.K., W.S.A., D.J., J.A.P., W.H.F.) · Department of Cardiology, Institut für Herzinfarktforschung Ludwigshafen, Germany (U.Z., M.H.) · Department of Cardiology, University Heart Center Lübeck, Medical Clinic II, University Hospital Schleswig-Holstein, Germany (H.T.) · German Cardiovascular Research Center (DZHK), Partner Site Hamburg/Kiel/Lübeck, Germany (H.T.) · AMIS Plus Data Center, University of Zurich, Switzerland (D.R., P.E.) · Department of Cardiology, Falun Hospital, Sweden (K.H.) · Department of Medical Sciences, Uppsala University, Sweden (K.H., S.J.) · Department of Cardiology, Academic Medical Center, University of Amsterdam, the Netherlands (B.E.C., J.P.S.H.) · Department of Cardiology, Galway University Hospital, SAOLTA Healthcare Group, National University of Ireland (D.M.) · Department of Cardiology, Ramsay Générale de Santé, Institut Cardiovasculaire Paris Sud, Hopital Privé Jacques Cartier, Massy, France (P.G.) · Department of Medicine, Division of Cardiology, David-Geffen School of Medicine, University of California at Los Angeles (G.C.F.) · and Department of Medicine, Division of Cardiology, Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA (D.L.B.). ·Circ Cardiovasc Interv · Pubmed #29146672.

ABSTRACT: BACKGROUND: The optimal revascularization strategy in patients with multivessel disease presenting with cardiogenic shock complicating ST-segment-elevation myocardial infarction remains unknown. METHODS AND RESULTS: Databases were searched from 1999 to October 2016. Studies comparing immediate/single-stage multivessel percutaneous coronary intervention (MV-PCI) versus culprit vessel-only PCI (CO-PCI) in patients with multivessel disease, ST-segment-elevation myocardial infarction, and cardiogenic shock were included. Primary end point was short-term (in-hospital or 30 days) mortality. Secondary end points included long-term mortality, cardiovascular death, reinfarction, and repeat revascularization. Safety end points were in-hospital stroke, renal failure, and major bleeding. The meta-analysis included 11 nonrandomized studies and 5850 patients (1157 MV-PCI and 4693 CO-PCI). There was no significant difference in short-term mortality with MV-PCI versus CO-PCI (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.81-1.43; CONCLUSIONS: This meta-analysis of nonrandomized studies suggests that in patients with cardiogenic shock complicating ST-segment-elevation myocardial infarction, there may be no significant benefit with single-stage MV-PCI compared with CO-PCI. Given the limitations of observational data, randomized trials are needed to determine the role of MV-PCI in this setting.

5 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 / Anonymous4670899. ·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.

6 Review Bioresorbable Stents in PCI. 2016

Lindholm, Daniel / James, Stefan. ·Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden. daniel.lindholm@ucr.uu.se. · Uppsala Clinical Research Center, Dag Hammarskjölds väg 14B, SE-752 37, Uppsala, Sweden. daniel.lindholm@ucr.uu.se. · Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden. · Uppsala Clinical Research Center, Dag Hammarskjölds väg 14B, SE-752 37, Uppsala, Sweden. ·Curr Cardiol Rep · Pubmed #27312934.

ABSTRACT: The evolution of percutaneous coronary intervention has been considerable. Coronary stents were introduced to avoid vessel recoil and reduce acute and late vessel complications. Later, drug-eluting stents were developed to decrease the neointimal hyperplasia associated with bare metal stents in order to reduce restenosis. However, very late stent thrombosis remains problematic, and the permanent presence of a metal stent could be associated with local inflammation and impaired vascular physiology. Thus, bioresorbable stents have been developed, to prevent recoil initially when this risk is the highest, with subsequent degradation over time, to avoid long-term complications of the presence of stents in the coronary vasculature. Here, we review the current status of bioresorbable stents in percutaneous coronary intervention (PCI), with focus on the platforms that have been studied the most: ABSORB, DESolve, and DREAMS. In terms of clinical outcomes, bioresorbable stents have not yet shown superiority compared with current generation drug-eluting stents, but rather a signal of increased stent thrombosis. Further development and longer-term studies are needed before the routine implementation of bioresorbable stents in clinical practice.

7 Review Report of a European Society of Cardiology-European Association of Percutaneous Cardiovascular Interventions task force on the evaluation of coronary stents in Europe: executive summary. 2015

Byrne, Robert A / Serruys, Patrick W / Baumbach, Andreas / Escaned, Javier / Fajadet, Jean / James, Stefan / Joner, Michael / Oktay, Semih / Jüni, Peter / Kastrati, Adnan / Sianos, George / Stefanini, Giulio G / Wijns, William / Windecker, Stephan. ·Deutsches Herzzentrum München, Technische Universität München, Munich, Germany. · Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands. · Bristol Heart Institute, Bristol, UK. · Interventional Cardiology, Hospital San Carlos, Madrid, Spain. · Interventional Cardiology, Clinique Pasteur, Toulouse, France. · Clinical Research Center, Uppsala University, Uppsala, Sweden. · CVPath Institute, Inc., Gaithersburg, USA. · Cardio Med Device Consultants, Baltimore, USA. · Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland. · AHEPA University Hospital, Thessaloniki, Greece. · Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland. · Cardiovascular Center O.L.V.Z., Aalst, Belgium. · Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland stephan.windecker@insel.ch. ·Eur Heart J · Pubmed #26071600.

ABSTRACT: The evaluation for European Union market approval of coronary stents falls under the Medical Device Directive that was adopted in 1993. Specific requirements for the assessment of coronary stents are laid out in supplementary advisory documents. In response to a call by the European Commission to make recommendations for a revision of the advisory document on the evaluation of coronary stents (Appendix 1 of MEDDEV 2.7.1), the European Society of Cardiology (ESC) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) established a Task Force to develop an expert advisory report. As basis for its report, the ESC-EAPCI Task Force reviewed existing processes, established a comprehensive list of all coronary drug-eluting stents that have received a CE mark to date, and undertook a systematic review of the literature of all published randomized clinical trials evaluating clinical and angiographic outcomes of coronary artery stents between 2002 and 2013. Based on these data, the TF provided recommendations to inform a new regulatory process for coronary stents. The main recommendations of the task force include implementation of a standardized non-clinical assessment of stents and a novel clinical evaluation pathway for market approval. The two-stage clinical evaluation plan includes recommendation for an initial pre-market trial with objective performance criteria (OPC) benchmarking using invasive imaging follow-up leading to conditional CE-mark approval and a subsequent mandatory, large-scale randomized trial with clinical endpoint evaluation leading to unconditional CE-mark. The data analysis from the systematic review of the Task Force may provide a basis for determination of OPC for use in future studies. This paper represents an executive summary of the Task Force's report.

8 Review STEMI guidelines: from formulation to implementation. 2012

Di Mario, Carlo / Syrseloudis, Dimitrios / James, Stefan / Viceconte, Nicola / Wijns, William. ·Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom. ·EuroIntervention · Pubmed #22917781.

ABSTRACT: -- No abstract --

9 Review Why don't we return to bare metal stents? 2008

Hess, Otto M / Karjalainen, Pasi / James, Stefan / Wallentin, Lars / de Winter, Robbert J. ·Swiss Cardiovascular Center, University Hospital, 3010 Bern, Switzerland. otto.hess@insel.ch ·EuroIntervention · Pubmed #19112775.

ABSTRACT: -- No abstract --

10 Clinical Trial The effect of CYP2C19 gene polymorphisms on the pharmacokinetics and pharmacodynamics of prasugrel 5-mg, prasugrel 10-mg and clopidogrel 75-mg in patients with coronary artery disease. 2014

Gurbel, P A / Bergmeijer, T O / Tantry, U S / ten Berg, J M / Angiolillo, D J / James, S / Lindahl, T L / Svensson, P / Jakubowski, J A / Brown, P B / Duvvuru, S / Sundseth, S / Walker, J R / Small, D / Moser, B A / Winters, K J / Erlinge, D. ·Paul A. Gurbel, MD, Sinai Center for Thrombosis Research, Cardiac Catheterization Laboratory, 2401 W. Belvedere Ave, Baltimore, MD 21215, USA, Tel.: +1 410 601 9600, Fax: +1 410 601 9601, E-mail: PGURBEL@LIFEBRIDGEHEALTH.ORG. ·Thromb Haemost · Pubmed #25008027.

ABSTRACT: CYP2C19 genotype has been shown to impact response to clopidogrel 75-mg but not prasugrel 10-mg. Here, we assessed effects of CYP2C19 metaboliser status on pharmacokinetics (PK) and pharmacodynamic (PD) responses to prasugrel 5-mg and 10-mg and clopidogrel 75-mg using data from two PK/PD studies in stable coronary artery disease (CAD) patients (GENERATIONS and FEATHER). Active metabolite concentrations (area under the curve, AUC[0-tlast]), maximum platelet aggregation (MPA) measured by light transmission aggregometry, vasodilator-stimulated phosphoprotein platelet reactivity index, and VerifyNow P2Y12-platelet reaction units (VN-PRU) were analysed by CYP2C19-predicted phenotype (extensive metaboliser [EM; N=154], *2-*8 non-carriers, vs reduced metaboliser [RM; N=41],*2-*8 carriers/*17 non-carriers). AUC(0-tlast) was unaffected by metaboliser status for prasugrel 5-mg and 10-mg (geometric mean EM/RM ratios 1.00, 95% confidence interval [CI]: 0.86,1.17, p>0.99; and 0.97, 95% CI:0.85,1.12, p=0.71, respectively), but was lower among RMs receiving clopidogrel 75-mg (1.37, 95% CI:1.14,1.65, p<0.001). Platelet reactivity was not significantly affected by CYP2C19 metaboliser status for prasugrel 5-mg, or for prasugrel 10-mg by MPA and VN-PRU, but for clopidogrel 75-mg was significantly higher in reduced metabolisers (all measures p<0.01). Prasugrel 10-mg showed greater antiplatelet effects vs clopidogrel 75-mg (all comparisons p<0.001). Prasugrel 5-mg showed greater antiplatelet effects vs clopidogrel 75-mg in RMs (all p<0.001), and comparable effects in EMs (all p≥0.37). In contrast to clopidogrel, prasugrel active metabolite PK was not influenced by CYP2C19 genotype. Antiplatelet effect for prasugrel 10-mg was greater irrespective of metaboliser status and for prasugrel 5-mg was greater for RMs and comparable for EMs as compared to clopidogrel 75-mg.

11 Clinical Trial Prasugrel 5 mg in the very elderly attenuates platelet inhibition but maintains noninferiority to prasugrel 10 mg in nonelderly patients: the GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients. 2013

Erlinge, David / Gurbel, Paul A / James, Stefan / Lindahl, Tomas L / Svensson, Peter / Ten Berg, Jurrien M / Foley, David P / Wagner, Henrik / Brown, Patricia B / Luo, Junxiang / Zhou, Chunmei / Moser, Brian A / Jakubowski, Joseph A / Small, David S / Winters, Kenneth J / Angiolillo, Dominick J. ·Department of Cardiology, Lund University, Lund, Sweden. david.erlinge@med.lu.se ·J Am Coll Cardiol · Pubmed #23747759.

ABSTRACT: OBJECTIVES: This study assessed pharmacodynamic (PD) response to the reduced prasugrel maintenance dose of 5 mg in very elderly (VE) patients (≥75 years of age). BACKGROUND: In the TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction 38) study prasugrel 10 mg reduced ischemic events versus clopidogrel 75 mg, but increased bleeding in VE patients. METHODS: We examined PD and active metabolite pharmacokinetics (PKs) with prasugrel 5 and 10 mg and clopidogrel 75 mg in a 3-period (12 days each) blinded, crossover study in VE (n = 73; mean: 79 ± 3 years of age) or (n = 82) nonelderly (NE) (≥45 to <65 years of age; mean: 56 ± 5 years of age) stable coronary artery disease (CAD) patients receiving background aspirin. Assays included light transmission aggregometry (LTA), VerifyNow P2Y12 (VN-P2Y12), and vasodilator-associated stimulated phosphoprotein (VASP). The primary comparison was noninferiority of maximum platelet aggregation (MPA) comparing the median for prasugrel 5 mg in VE versus the 75th percentile for prasugrel 10 mg in NE, using a pre-specified 1-sided 97.5% confidence interval for the difference <15%. RESULTS: Prasugrel 5 mg in VE met the primary PD noninferiority criterion versus prasugrel 10 mg in NE. For prasugrel 5 mg, MPA was significantly lower (57 ± 14%) than clopidogrel (63 ± 14%; p < 0.001) in VE but higher than prasugrel 10 mg in NE (46 ± 12%; p < 0.001). PD response by LTA, VN-P2Y12, and VASP during all treatments appeared similar between age cohorts. Prasugrel 5 mg resulted in fewer VE poor responders than clopidogrel. Rates of mild bleeding were higher with prasugrel 10 mg but similar for prasugrel 5 mg versus clopidogrel 75 mg. CONCLUSIONS: In aspirin-treated stable CAD patients, prasugrel 5 mg in VE attenuated platelet inhibition while meeting pre-specified noninferiority criterion versus prasugrel 10 mg in NE, with significantly better PD response and fewer poor responders compared to clopidogrel 75 mg in VE. (Comparison of Prasugrel and Clopidogrel in Very Elderly and Non-Elderly Patients With Stable Coronary Artery Disease [GENERATIONS]; NCT01107912).

12 Clinical Trial Randomized comparison of final kissing balloon dilatation versus no final kissing balloon dilatation in patients with coronary bifurcation lesions treated with main vessel stenting: the Nordic-Baltic Bifurcation Study III. 2011

Niemelä, Matti / Kervinen, Kari / Erglis, Andrejs / Holm, Niels R / Maeng, Michael / Christiansen, Evald H / Kumsars, Indulis / Jegere, Sanda / Dombrovskis, Andis / Gunnes, Pål / Stavnes, Sindre / Steigen, Terje K / Trovik, Thor / Eskola, Markku / Vikman, Saila / Romppanen, Hannu / Mäkikallio, Timo / Hansen, Knud N / Thayssen, Per / Aberge, Lars / Jensen, Lisette O / Hervold, Anders / Airaksinen, Juhani / Pietilä, Mikko / Frobert, Ole / Kellerth, Thomas / Ravkilde, Jan / Aarøe, Jens / Jensen, Jan S / Helqvist, Steffen / Sjögren, Iwar / James, Stefan / Miettinen, Heikki / Lassen, Jens F / Thuesen, Leif / Anonymous1020682. ·Division of Cardiology, Department of Internal Medicine, University of Oulu, Finland. matti.niemela@ppshp.fi ·Circulation · Pubmed #21173348.

ABSTRACT: BACKGROUND: It is unknown whether the preferred 1-stent bifurcation stenting approach with stenting of the main vessel (MV) and optional side branch stenting using drug-eluting stents should be finalized by a kissing balloon dilatation (FKBD). Therefore, we compared strategies of MV stenting with and without FKBD. METHODS AND RESULTS: We randomized 477 patients with a bifurcation lesion to FKBD (n=238) or no FKBD (n=239) after MV stenting. The primary end point was major adverse cardiac events: cardiac death, non-procedure-related index lesion myocardial infarction, target lesion revascularization, or stent thrombosis within 6 months. The 6-month major adverse cardiac event rates were 2.1% and 2.5% (P=1.00) in the FKBD and no-FKBD groups, respectively. Procedure and fluoroscopy times were longer and more contrast media was needed in the FKBD group than in the no-FKBD group. Three hundred twenty-six patients had a quantitative coronary assessment. At 8 months, the rate of binary (re)stenosis in the entire bifurcation lesion (MV and side branch) was 11.0% versus 17.3% (P=0.11), in the MV was 3.1% versus 2.5% (P=0.68), and in the side branch was 7.9% versus 15.4% (P=0.039) in the FKBD versus no-FKBD groups, respectively. In patients with true bifurcation lesions, the side branch restenosis rate was 7.6% versus 20.0% (P=0.024) in the FKBD and no-FKBD groups, respectively. CONCLUSIONS: MV stenting strategies with and without FKBD were associated with similar clinical outcomes. FKBD reduced angiographic side branch (re)stenosis, especially in patients with true bifurcation lesions. The simple no-FKBD procedures resulted in reduced use of contrast media and shorter procedure and fluoroscopy times. Long-term data on stent thrombosis are needed. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00914199.

13 Clinical Trial Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo. 2008

Erlinge, David / Varenhorst, Christoph / Braun, Oscar O / James, Stefan / Winters, Kenneth J / Jakubowski, Joseph A / Brandt, John T / Sugidachi, Atsuhiro / Siegbahn, Agneta / Wallentin, Lars. ·Department of Cardiology, Lund University, Lund, Sweden. david.erlinge@med.lu.se ·J Am Coll Cardiol · Pubmed #19055987.

ABSTRACT: OBJECTIVES: We evaluated the prevalence and mechanism of poor responsiveness to clopidogrel and prasugrel in coronary artery disease patients with and without diabetes. BACKGROUND: Low platelet inhibition by clopidogrel is associated with ischemic clinical events. A higher 600-mg loading dose (LD) has been advocated to increase responsiveness to clopidogrel. METHODS: In this study, 110 aspirin-treated patients were randomized to double-blind treatment with clopidogrel 600 mg LD/75 mg maintenance dose (MD) for 28 days or prasugrel 60 mg LD/10 mg MD for 28 days. Pharmacodynamic (PD) response was evaluated by light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation. The PD poor responsiveness was defined with 4 definitions previously associated with worse clinical outcomes. Active metabolites (AM) of clopidogrel and prasugrel were measured. Clopidogrel AM was added ex vivo. RESULTS: The proportion of patients with poor responsiveness was greater in the clopidogrel group for all definitions at all time points from 1 h to 29 days. Poor responders had significantly lower plasma AM levels compared with responders. Patients with diabetes were over-represented in the poor-responder groups and had significantly lower levels of AM. Platelets of both poor responders and diabetic patients responded fully to AM added ex vivo. CONCLUSIONS: Prasugrel treatment results in significantly fewer PD poor responders compared with clopidogrel after a 600-mg clopidogrel LD and during MD. The mechanism of incomplete platelet inhibition in clopidogrel poor-responder groups and in diabetic patients is lower plasma levels of its AM and not differences in platelet P2Y(12) receptor function.

14 Article Stent thrombosis rates the first year and beyond with new- and old-generation drug-eluting stents compared to bare metal stents. 2018

Varenhorst, Christoph / Lindholm, Martin / Sarno, Giovanna / Olivecrona, Göran / Jensen, Ulf / Nilsson, Johan / Carlsson, Jörg / James, Stefan / Lagerqvist, Bo. ·Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. christoph.varenhorst@medsci.uu.se. · Department of Medical Sciences, Cardiology, Uppsala University, Dag Hammarsköldsväg 14B, 75337, Uppsala, Sweden. christoph.varenhorst@medsci.uu.se. · Department of Internal Medicine, Cardiology, Västerås County Hospital, Västerås, Sweden. · Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. · Department of Medical Sciences, Cardiology, Uppsala University, Dag Hammarsköldsväg 14B, 75337, Uppsala, Sweden. · Department of Cardiology, Lund University, Lund, Sweden. · Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden. · Department of Cardiology, Heart Centre, Umeå University, Umeå, Sweden. · Faculty of Health and Life Sciences, Linnaeus University, Kalmar, Sweden. ·Clin Res Cardiol · Pubmed #29667015.

ABSTRACT: OBJECTIVES: Old-generation drug-eluting coronary stents (o-DES) have despite being safe and effective been associated with an increased propensity of late stent thrombosis (ST). We evaluated ST rates in o-DES, new-generation DES (n-DES) and bare metal stents (BMS) the first year (< 1 year) and beyond 1 year (> 1 year). METHODS: We evaluated all implantations with BMS, o-DES (Cordis Cypher, Boston Scientific Taxus Liberté and Medtronic Endeavor) and n-DES in the Swedish coronary angiography and angioplasty registry (SCAAR) between 1 January 2007 and 8 January 2014 (n = 207 291). All cases of ST (n = 2 268) until 31 December 2014 were analyzed. RESULTS: The overall risk of ST was lower in both n-DES and o-DES compared with BMS up to 1 year (n-DES versus BMS: adjusted risk ratio (RR) 0.48 (0.41-0.58) and o-DES versus BMS: 0.56 (0.46-0.67), both p < 0.001). From 1 year after stent implantation and onward, the risk for ST was higher in o-DES compared with BMS [adjusted RR, 1.82 (1.47-2.25], p < 0.001). N-DES were associated with similar low ST rates as BMS from 1 year and onward [adjusted RR 1.21 (0.94-1.56), p = 0.135]. CONCLUSION: New-generation DES were associated with lower ST rates in comparison to BMS during the first-year post-stenting. After 1 year, n-DES and BMS were associated with similar ST rates. TRIAL REGISTRATION: This study was a retrospective observational study and as such did not require clinical trial database registration.

15 Article Treatment Trends, Effectiveness, and Safety of Statins on Lipid Goal Attainment in Chinese Percutaneous Coronary Intervention Patients: a Multicenter, Retrospective Cohort Study. 2017

Chen, Yundai / Li, Dandan / Jing, Jing / Yan, Hongbing / Liu, Jinghua / Shen, Zhujun / James, Stefan / Varenhorst, Christoph. ·Department of Cardiology, The Chinese PLA General Hospital (301 Hospital), Beijing, People's Republic of China. Electronic address: cyundai@vip.163.com. · Department of Cardiology, The Chinese PLA General Hospital (301 Hospital), Beijing, People's Republic of China. · National Center for Cardiovascular Diseases, Cardiovascular Institute and FuWai Hospital, Beijing, People's Republic of China. · Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People's Republic of China. · Department of Cardiology, Peking Union Medical College Hospital, Beijing, People's Republic of China. · Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. ·Clin Ther · Pubmed #28807393.

ABSTRACT: PURPOSE: Limited data exist on the use of statins in Chinese patients with coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI). We therefore conducted this study to observe the usage trend and the effectiveness of statins on LDL-C goal attainment and other lipid parameters among PCI-treated patients. METHODS: This multicenter, retrospective, observational, longitudinal cohort study was conducted in PCI-treated patients with CAD between July 1, 2011, and February 28, 2015. Primary study outcomes included statin treatment pattern after PCI and proportion of patients achieving target (LDL-C) levels 1 month after PCI and initiating statin therapy. FINDINGS: Data were analyzed for 2708 patients (mean age, 59 [10] years; median body mass index, 25.6 [4.0] kg/m IMPLICATIONS: In real-world, PCI-treated Chinese patients, atorvastatin and rosuvastatin were the most prescribed statins. Compared with atorvastatin 20 mg, rosuvastatin 10 mg was associated with greater LDL-C reductions and achievement of LDL-C targets in a higher percentage of patients. This analysis of real-world data shows that both rosuvastatin and atorvastatin were well tolerated and seemed to be suitable drugs for controlling lipid levels and preventing CVD risk in post-PCI Chinese patients with CAD.

16 Article Real-life clinical outcomes with everolimus eluting platinum chromium stent with an abluminal biodegradable polymer in patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). 2017

Sarno, Giovanna / Lagerqvist, Bo / Olivecrona, Göran / Varenhorst, Christoph / Danielewicz, Mikael / Hambraeus, Kristina / Lindholm, Daniel / Råmunddal, Truls / Witt, Nils / James, Stefan. ·Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. · UCR, Uppsala Clinical Research Center, Uppsala, Sweden. · Department of Cardiology, Lund University Hospital, Lund, Sweden. · Department of Cardiology, Karlstad Hospital, Karlstad, Sweden. · Department of Cardiology, Falun Lasarett, Falun, Sweden. · Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden. · Department of Cardiology, Södersjukhuset University Hospital, Stockholm, Sweden. ·Catheter Cardiovasc Interv · Pubmed #28544146.

ABSTRACT: BACKGROUND: No previous studies have evaluated the performance of the Synergy stent in a large real-life population. OBJECTIVES: To describe the initial real-life experience with a novel everolimus eluting platinum chromium stent with abluminal biodegradable polymer (SYNERGY) in unselected patients from a nationwide registry. METHODS: All implanted Synergy stents were compared with other new generation drug eluting stents (n-DES) with >1,000 implantations in Sweden between March 2013 and October 2015. Restenosis, definite stent thrombosis (ST), myocardial infarction (MI) and death rates were assessed using propensity score and Cox regression analyses. RESULTS: A total of 7,886 of Synergy stents and 64,429 other n-DES (BioMatrix, N = 1,953; Orsiro, N = 4,946; Promus Element Plus, N= 2,543; Promus Premier, N= 20,414; Xience Xpedition, N= 7,971, Resolute/Resolute Integrity, N = 19,021; Ultimaster, N = 1,156; Resolute Onyx, N = 6,425) were implanted in 42,357 procedures. Restenosis and stent thrombosis occurred in 642 and 314 cases, respectively, in the overall population at 1 year. The cumulative rate of restenosis (1.1% vs. 1.0%, adjusted HR: 1.24 95% CI: 0.88-1.75; P = 0.21) and ST (0.4% vs. 0.5%, adjusted HR: 0.97; 95% CI: 0.63-1.50; P = 0.17) up to 1 year was low in both the Synergy group and the other n-DES group. Death occurred in 5.2% versus 4.5% (adjusted HR: 1.14; 95% CI: 0.96-1.36; P = 0.11) and MI in 3.2% versus 3.5%, (adjusted HR: 1.11; 95% CI: 0.93-1.33; P = 0.24) up to 1 year. CONCLUSIONS: In a large real-life population the Synergy stent appears to be safe and effective with a low rate of restenosis and ST comparable with other n-DES. © 2017 Wiley Periodicals, Inc.

17 Article Intravascular Ultrasound Guidance Is Associated With Better Outcome in Patients Undergoing Unprotected Left Main Coronary Artery Stenting Compared With Angiography Guidance Alone. 2017

Andell, Pontus / Karlsson, Sofia / Mohammad, Moman A / Götberg, Matthias / James, Stefan / Jensen, Jens / Fröbert, Ole / Angerås, Oskar / Nilsson, Johan / Omerovic, Elmir / Lagerqvist, Bo / Persson, Jonas / Koul, Sasha / Erlinge, David. ·From the Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Sweden (P.A., S.K., M.A.M., M.G., S.K., D.E.) · Department of Medical Sciences, Uppsala University, Sweden (S.J., B.L.) · Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Unit of Medicine, Capio St Görans Sjukhus, Stockholm, Sweden (J.J.) · Department of Cardiology, Faculty of Health, Örebro University, Sweden (O.F.) · Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden (O.A., E.O.) · University and Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden (O.A., E.O.) · Department of Cardiology, Umeå University Hospital, Heart Centre, Sweden (J.N.) · and Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden (J.P.). ·Circ Cardiovasc Interv · Pubmed #28487356.

ABSTRACT: BACKGROUND: Small observational studies have indicated better outcome with intravascular ultrasound (IVUS) guidance when performing unprotected left main coronary artery (LMCA) percutaneous coronary intervention (PCI), but the overall picture remains inconclusive and warrants further investigation. We studied the impact of IVUS guidance on outcome in patients undergoing unprotected LMCA PCI in a Swedish nationwide observational study. METHODS AND RESULTS: Patients who underwent unprotected LMCA PCI between 2005 and 2014 because of stable coronary artery disease or acute coronary syndrome were included from the nationwide SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Of 2468 patients, IVUS guidance was used in 621 (25.2%). The IVUS group was younger (median age, 70 versus 75 years) and had fewer comorbidities but more complex lesions. IVUS was associated with larger stent diameters (median, 4 mm versus 3.5 mm). After adjusting for potential confounders, IVUS was associated with significantly lower occurrence of the primary composite end point of all-cause mortality, restenosis, or definite stent thrombosis (hazard ratio, 0.65; 95% confidence interval, 0.50-0.84) and all-cause mortality alone (hazard ratio, 0.62; 95% confidence interval, 0.47-0.82). In 340 propensity score-matched pairs, IVUS was also associated with significantly lower occurrence of the primary end point (hazard ratio, 0.54; 95% confidence interval, 0.37-0.80). CONCLUSIONS: IVUS was associated with an independent and significant outcome benefit when performing unprotected LMCA PCI. Potential mediators of this benefit include larger and more appropriately sized stents, perhaps translating into lower risk of subsequent stent thrombosis. Although residual confounding cannot be ruled out, our findings indicate a possible hazard when performing unprotected LMCA PCI without IVUS guidance.

18 Article Potent P2Y 2017

Lau, Emily S / Braunwald, Eugene / Murphy, Sabina A / Wiviott, Stephen D / Bonaca, Marc P / Husted, Steen / James, Stefan K / Wallentin, Lars / Clemmensen, Peter / Roe, Matthew T / Ohman, E Magnus / Harrington, Robert A / Mega, Jessica L / Bhatt, Deepak L / Sabatine, Marc S / O'Donoghue, Michelle L. ·Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. · TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. · Department of Cardiology, Århus University Hospital, Århus, Denmark. · Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. · Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, Germany; Department of Medicine, Nykoebing F Hospital, University of Southern Denmark, Odense, Denmark. · Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina. · Department of Medicine, Stanford University, Stanford, California. · Verily Life Sciences, Mountain View, California. · TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: modonoghue@partners.org. ·J Am Coll Cardiol · Pubmed #28335837.

ABSTRACT: BACKGROUND: Sex-specific differences in response to antiplatelet therapies have been described. Whether women and men derive comparable benefit from intensification of antiplatelet therapy remains uncertain. OBJECTIVES: The study investigated the efficacy and safety of the potent P2Y METHODS: A collaborative sex-specific meta-analysis was conducted of phase III or IV randomized trials of potent P2Y RESULTS: Potent P2Y CONCLUSIONS: In randomized trials, the efficacy and safety of the potent P2Y

19 Article Long-Term Outcome of Incomplete Revascularization After Percutaneous Coronary Intervention in SCAAR (Swedish Coronary Angiography and Angioplasty Registry). 2016

Hambraeus, Kristina / Jensevik, Karin / Lagerqvist, Bo / Lindahl, Bertil / Carlsson, Roland / Farzaneh-Far, Ramin / Kellerth, Thomas / Omerovic, Elmir / Stone, Gregg / Varenhorst, Christoph / James, Stefan. ·Department of Cardiology, Falun Hospital, Falun, Sweden; Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden. Electronic address: Kristina.hambraeus@ltdalarna.se. · Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. · Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. · PCI Unit, Department of Cardiology, Central Hospital, Karlstad, Sweden. · Gilead Sciences, Inc., Foster City, California. · Department of Cardiology, University Hospital, Örebro, Sweden. · Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. · New York Presbyterian Hospital, Columbia University Medical Center, and the Cardiovascular Research Foundation, New York, New York. ·JACC Cardiovasc Interv · Pubmed #26847112.

ABSTRACT: OBJECTIVES: The aim of this study was to describe current practice regarding completeness of revascularization in patients with multivessel disease undergoing percutaneous coronary intervention (PCI) and to investigate the association of incomplete revascularization (IR) with death, repeat revascularization, and myocardial infarction (MI) in a large nationwide registry. BACKGROUND: The benefits of multivessel PCI are controversial. METHODS: Between 2006 and 2010 we identified 23,342 patients with multivessel disease in the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) and merged data with official Swedish health data registries. IR was defined as any nontreated significant (60%) stenosis in a coronary artery supplying >10% of the myocardium. RESULTS: Patients with IR (n = 15,165) were older, had more extensive coronary disease, and more often had ST-segment elevation MI at presentation than those with complete revascularization (CR) (n = 8,177). All-cause 1-year mortality, MI, and repeat revascularization were higher in IR than CR: 7.1% versus 3.8%, 10.4% versus 6.0%, and 20.5% versus 8.5%, respectively. Propensity score methodology was used in the adjusted analyses. Adjusted hazard ratio (HR) for the composite of death, MI, or repeat revascularization at 1 year was higher in IR than CR: 2.12 (95% confidence interval [CI]: 1.98 to 2.28; p < 0.0001). Adjusted HR for death and the combination of death/MI were 1.29 (95% CI: 1.12 to 1.49; p = 0.0005) and 1.42 (95% CI: 1.30 to 1.56; p < 0.0001), respectively. CONCLUSIONS: Incomplete revascularization at the time of hospital discharge in patients with multivessel disease undergoing PCI is associated with a high risk of recurrent 1-year adverse cardiac events.

20 Article Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomised, double-blind, placebo-controlled trial. 2016

Weisz, Giora / Généreux, Philippe / Iñiguez, Andres / Zurakowski, Aleksander / Shechter, Michael / Alexander, Karen P / Dressler, Ovidiu / Osmukhina, Anna / James, Stefan / Ohman, E Magnus / Ben-Yehuda, Ori / Farzaneh-Far, Ramin / Stone, Gregg W / Anonymous7500845. ·Shaare Zedek Medical Center, Jerusalem, Israel; New York Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA; Cardiovascular Research Foundation, New York, NY, USA. Electronic address: weiszg@szmc.org.il. · Cardiovascular Research Foundation, New York, NY, USA; Hôpital du Sacré-Coeur de Montreal, Université de Montreal, Montreal, QC, Canada. · Hospital de Meixoeiro, Vigo, Spain. · American Heart of Poland SA, Katowice, Poland. · Chaim Sheba Medical Center, Tel Hashomer, Israel. · Duke Clinical Research Institute and Duke University, Durham, NC, USA. · Cardiovascular Research Foundation, New York, NY, USA. · Gilead Sciences, Foster City, CA, USA. · Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden. · New York Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA; Cardiovascular Research Foundation, New York, NY, USA. ·Lancet · Pubmed #26474810.

ABSTRACT: BACKGROUND: Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events. We aimed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention. METHODS: We performed this multicentre, randomised, parallel-group, double-blind, placebo-controlled, event-driven trial at 245 centres in 15 countries in Europe, Israel, Russia, and the USA. Patients (aged ≥18 years) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention (defined as one or more lesions with ≥50% diameter stenosis in a coronary artery ≥2 mm diameter) were randomly assigned (1:1), via an interactive web-based block randomisation system (block sizes of ten), to receive either twice-daily oral ranolazine 1000 mg or matching placebo. Randomisation was stratified by diabetes history (presence vs absence) and acute coronary syndrome presentation (acute coronary syndrome vs non-acute coronary syndrome). Study investigators, including all research teams, and patients were masked to treatment allocation. The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01442038. FINDINGS: Between Nov 3, 2011, and May 27, 2013, we randomly assigned 2651 patients to receive ranolazine (n=1332) or placebo (n=1319); 2604 (98%) patients comprised the full analysis set. After a median follow-up of 643 days (IQR 575-758), the composite primary endpoint occurred in 345 (26%) patients assigned to ranolazine and 364 (28%) patients assigned to placebo (hazard ratio 0·95, 95% CI 0·82-1·10; p=0·48). Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups. 189 (14%) patients in the ranolazine group and 137 (11%) patients in the placebo group discontinued study drug because of an adverse event (p=0·04). INTERPRETATION: Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention. Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population. FUNDING: Gilead Sciences, Menarini.

21 Article Relationship Between Cancer and Cardiovascular Outcomes Following Percutaneous Coronary Intervention. 2015

Hess, Connie N / Roe, Matthew T / Clare, Robert M / Chiswell, Karen / Kelly, Joseph / Tcheng, James E / Hagstrom, Emil / James, Stefan K / Khouri, Michel G / Hirsch, Bradford R / Kong, David F / Abernethy, Amy P / Krucoff, Mitchell W. ·Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC (C.N.H., M.T.R., J.E.T., M.G.K., D.F.K., M.W.K.) Duke Clinical Research Institute, Durham, NC (C.N.H., M.T.R., R.M.C., K.C., J.E.T., B.R.H., D.F.K., M.W.K.). · Duke Clinical Research Institute, Durham, NC (C.N.H., M.T.R., R.M.C., K.C., J.E.T., B.R.H., D.F.K., M.W.K.). · Center for Learning Healthcare, Duke Clinical Research Institute, Durham, NC (J.K., A.P.A.). · Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Sweden (E.H., S.K.J.). · Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC (C.N.H., M.T.R., J.E.T., M.G.K., D.F.K., M.W.K.). · Duke Clinical Research Institute, Durham, NC (C.N.H., M.T.R., R.M.C., K.C., J.E.T., B.R.H., D.F.K., M.W.K.) Duke Cancer Institute, Durham, NC (B.R.H., A.P.A.). · Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC (A.P.A.) Center for Learning Healthcare, Duke Clinical Research Institute, Durham, NC (J.K., A.P.A.) Duke Cancer Institute, Durham, NC (B.R.H., A.P.A.). ·J Am Heart Assoc · Pubmed #26150477.

ABSTRACT: BACKGROUND: Cardiovascular disease and cancer increasingly coexist, yet relationships between cancer and long-term cardiovascular outcomes post-percutaneous coronary intervention (PCI) are not well studied. METHODS AND RESULTS: We examined stented PCI patients at Duke (1996-2010) using linked data from the Duke Information Systems for Cardiovascular Care and the Duke Tumor Registry (a cancer treatment registry). Our primary outcome was cardiovascular mortality. Secondary outcomes included composite cardiovascular mortality, myocardial infarction, or repeat revascularization and all-cause mortality. We used adjusted cause-specific hazard models to examine outcomes among cancer patients (cancer treatment pre-PCI) versus controls (no cancer treatment pre-PCI). Cardiovascular mortality was explored in a cancer subgroup with recent (within 1 year pre-PCI) cancer and in post-PCI cancer patients using post-PCI cancer as a time-dependent variable. Among 15 008 patients, 3.3% (n=496) were cancer patients. Observed rates of 14-year cardiovascular mortality (31.4% versus 27.7%, P=0.31) and composite cardiovascular death, myocardial infarction, or revascularization (51.1% versus 55.8%, P=0.37) were similar for cancer versus control groups; all-cause mortality rates were higher (79.7% versus 49.3%, P<0.01). Adjusted risk of cardiovascular mortality was similar for cancer patients versus controls (hazard ratio 0.95; 95% CI 0.76 to 1.20) and for patients with versus without recent cancer (hazard ratio 1.46; 95% CI 0.92 to 2.33). Post-PCI cancer, present in 4.3% (n=647) of patients, was associated with cardiovascular mortality (adjusted hazard ratio 1.51; 95% CI 1.11 to 2.03). CONCLUSIONS: Cancer history was present in a minority of PCI patients but was not associated with worse long-term cardiovascular outcomes. Further investigation into PCI outcomes in this population is warranted.

22 Article Quantitative assessment of myocardial perfusion in the detection of significant coronary artery disease: cutoff values and diagnostic accuracy of quantitative [(15)O]H2O PET imaging. 2014

Danad, Ibrahim / Uusitalo, Valtteri / Kero, Tanja / Saraste, Antti / Raijmakers, Pieter G / Lammertsma, Adriaan A / Heymans, Martijn W / Kajander, Sami A / Pietilä, Mikko / James, Stefan / Sörensen, Jens / Knaapen, Paul / Knuuti, Juhani. ·Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands. · Turku University Hospital and University of Turku, Turku, Finland. · Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Institute of Medical Sciences, Uppsala University, Uppsala, Sweden. · Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, the Netherlands. · Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands. · Department of Cardiology, Institute of Medical Sciences, Uppsala University, Uppsala, Sweden. · Turku University Hospital and University of Turku, Turku, Finland. Electronic address: juhani.knuuti@utu.fi. ·J Am Coll Cardiol · Pubmed #25277618.

ABSTRACT: BACKGROUND: Recent studies have demonstrated improved diagnostic accuracy for detecting coronary artery disease (CAD) when myocardial blood flow (MBF) is quantified in absolute terms, but there are no uniformly accepted cutoff values for hemodynamically significant CAD. OBJECTIVES: The goal of this study was to determine cutoff values for absolute MBF and to evaluate the diagnostic accuracy of quantitative [(15)O]H2O positron emission tomography (PET). METHODS: A total of 330 patients underwent both quantitative [(15)O]H2O PET imaging and invasive coronary angiography in conjunction with fractional flow reserve measurements. A stenosis >90% and/or fractional flow reserve ≤0.80 was considered obstructive; a stenosis <30% and/or fractional flow reserve >0.80 was nonobstructive. RESULTS: Hemodynamically significant CAD was diagnosed in 116 (41%) of 281 patients who fulfilled study criteria for CAD. Resting perfusion was 1.00 ± 0.25 and 0.92 ± 0.23 ml/min/g in regions supplied by nonstenotic and significantly stenosed vessels, respectively (p < 0.001). During stress, perfusion increased to 3.26 ± 1.04 ml/min/g and 1.73 ± 0.67 ml/min/g, respectively (p < 0.001). The optimal cutoff values were 2.3 and 2.5 for hyperemic MBF and myocardial flow reserve, respectively. For MBF, these cutoff values showed a sensitivity, specificity, and accuracy for detecting significant CAD of 89%, 84%, and 86%, respectively, at a per-patient level and 87%, 85%, and 85% at a per-vessel level. The corresponding myocardial flow reserve values were 86%, 72%, and 78% (per patient) and 80%, 82%, and 81% (per vessel). Age and sex significantly affected diagnostic accuracy of quantitative PET. CONCLUSIONS: Quantitative MBF measurements with the use of [(15)O]H2O PET provided high diagnostic performance, but both sex and age should be taken into account.

23 Article The influence of body size on the pharmacodynamic and pharmacokinetic response to clopidogrel and prasugrel: a retrospective analysis of the FEATHER study. 2014

Jakubowski, Joseph A / Angiolillo, Dominick J / Zhou, Chunmei / Small, David S / Moser, Brian A / Ten Berg, Jurrien M / Brown, Patricia B / James, Stefan / Winters, Kenneth J / Erlinge, David. ·Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: joseph@lilly.com. · Cardiovascular Research Center at University of Florida College of Medicine Jacksonville, FL, USA. · Eli Lilly and Company, Indianapolis, IN, USA. · St. Antonius Hospital, Nieuwegein, The Netherlands. · Uppsala Clinical Research Center, Uppsala, Sweden. · Lund University, Lund, Sweden. ·Thromb Res · Pubmed #25022828.

ABSTRACT: INTRODUCTION: Patients treated with clopidogrel who have higher body size exhibit greater platelet reactivity than patients with lower body size. In a retrospective analysis of the FEATHER trial, we examined the relationship between platelet response to thienopyridines clopidogrel 75 mg (Clop-75), prasugrel 5mg (Pras-5), and prasugrel 10mg (Pras-10) using 3 body size indices: body weight (BW), body mass index (BMI), and body surface area (BSA). Relationships were assessed as continuous variables and as 4 incremental body size groups. MATERIALS AND METHODS: Aspirin-treated patients with stable coronary artery disease (N=72) and a BW range of 45-134 kg received Clop-75, Pras-5, and Pras-10 in a 3-period, blinded, cross-over study. Platelet assays included maximum platelet aggregation (MPA) to 20μM ADP by light transmission aggregometry, VerifyNow-P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation platelet reactivity index (PRI). Exposure to active metabolites (AMs) was also assessed. RESULTS: Body size was a determinant of AM exposure and residual platelet reactivity regardless of type and dose of thienopyridine. BW and BSA demonstrated marginally stronger correlations with platelet reactivity; VASP-PRI demonstrated a stronger correlation with the body size than the other tests. Correlation coefficients ranged from a high of 0.64 (BW vs. PRI on Pras-5) to a low of 0.34 (BMI vs. MPA on Pras-10), but all were statistically significant (p<0.01). CONCLUSIONS: Using a comprehensive selection of body size indices, AM exposures, platelet function tests, and thienopyridine doses, we demonstrated a consistent inverse relationship between body size and response to clopidogrel and prasugrel.

24 Article Clopidogrel metaboliser status based on point-of-care CYP2C19 genetic testing in patients with coronary artery disease. 2014

Erlinge, David / James, Stefan / Duvvuru, Suman / Jakubowski, Joseph A / Wagner, Henrik / Varenhorst, Christoph / Tantry, Udaya S / Brown, Patricia B / Small, David / Moser, Brian A / Sundseth, Scott S / Walker, Joseph R / Winters, Kenneth J / Gurbel, Paul A. ·David Erlinge, Dept. of Cardiology, Lund University, Skane University Hospital, Lund; 221 85 Lund, Sweden, Tel: +46 46172597, Fax: +46 46157857, E-mail: david.erlinge@med.lu.se. ·Thromb Haemost · Pubmed #24402637.

ABSTRACT: We compared results obtained with the Nanosphere Verigene® System, a novel point-of-care (POC) genetic test capable of analysing 11 CYP2C19 variants within 3 hours, to an established, validated genotyping method (Affymetrix™ DMET+; reference assay) for identifying extensive and reduced metabolisers of clopidogrel. Based on genotyping, patients (N=82) with stable coronary artery disease on clopidogrel 75 mg daily were defined as extensive metabolisers (*1/*1, *1/*17, *17/*17), reduced metabolisers (*1/*2, *1/*8, *2/*2, *2/*3), or of indeterminate metaboliser status (*2/*17). Pharmacokinetic exposure to clopidogrel's active metabolite and pharmacodynamic measures with P2Y12 reaction units (PRU) (VerifyNow®P2Y12 assay) and VASP PRI (PRI) were also assessed. There was a 99.9% overall concordance of marker-level data between the Nanosphere Verigene and DMET+ systems in identifying the CYP2C19 variants and 100% agreement in classifying the patients as extensive (n=59) or reduced metabolisers (n=15). Extensive metabolisers had significantly higher active metabolite exposure than reduced metabolisers (LS means 12.6 ng*h/ml vs 7.7 ng*h/ml; p<0.001). Extensive metabolisers also had lower PRU (LS means 158 vs 212; p=0.003) and VASP PRI (LS means 48% vs 63%, p=0.01) compared to reduced metabolisers. Rates of high on-treatment platelet reactivity were higher in reduced metabolisers compared to extensive metabolisers (VASP PRI ≥ 50%: 79% vs 47%; PRU >235: 33% vs 16%). The Nanosphere Verigene CBS system identified 11 CYP2C19 alleles in less than 3 hours with a high degree of accuracy when compared to a conventional method, and was further validated against pharmacokinetic and pharmacodynamic phenotypes.

25 Article Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study. 2014

Storey, Robert F / James, Stefan K / Siegbahn, Agneta / Varenhorst, Christoph / Held, Claes / Ycas, Joseph / Husted, Steen E / Cannon, Christopher P / Becker, Richard C / Steg, Ph Gabriel / Åsenblad, Nils / Wallentin, Lars. ·Department of Cardiovascular Science, University of Sheffield , Sheffield , UK . ·Platelets · Pubmed #24127651.

ABSTRACT: In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.

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