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1. C5 Variant rs10985126 is Associated with Mortality in Patients with Symptomatic Coronary Artery Disease

Author

Henes JK, Groga-Bada P, Schaeffeler E, Winter S, Hack L, Zdanyte M, Mueller K, Droppa M, Stimpfle F, Gawaz M, Langer H, Schwab M, Geisler T, and Rath D

Subjects
coronary artery disease, snps, complement c5, prognostic factors, Therapeutics. Pharmacology, RM1-950
Abstract

Jessica Kristin Henes,1,* Patrick Groga-Bada,1,* Elke Schaeffeler,2,3 Stefan Winter,2,3 Luis Hack,1 Monika Zdanyte,1 Karin Mueller,1 Michal Droppa,1 Fabian Stimpfle,1 Meinrad Gawaz,1 Harald Langer,4 Matthias Schwab,2,3,5,6 Tobias Geisler,1 Dominik Rath1 1Department of Cardiology, University Hospital Tuebingen, Tuebingen, Germany; 2Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; 3University of Tuebingen, Tuebingen, Germany; 4Department of Cardiology, Angiology and Intensive Care, University Hospital Luebeck, Luebeck, Germany; 5Department of Clinical Pharmacology, University Hospital Tuebingen, Tuebingen, Germany; 6Department of Pharmacy and Biochemistry, University of Tuebingen, Tuebingen, Germany*These authors contributed equally to this workCorrespondence: Tobias GeislerMedizinische Klinik III, Department Cardiology and Cardiovascular Research, Otfried-Müller-Strasse 10, Tübingen, 72076 Tel +49 7071/29-8 36 88Fax +49 7071/29-57 49Email tobias.geisler@med.uni-tuebingen.deBackground: Complement component 5a (C5a) is a highly potent anaphylatoxin with a variety of pro-inflammatory effects. C5a contributes to progression of atherosclerosis and inhibition of the receptor (C5aR) might offer a therapeutic strategy in this regard. Single nucleotide polymorphisms (SNPs) of the C5 gene may modify protein expression levels and therefore function of C5a and C5aR. This study aimed to examine associations between clinically relevant C5a SNPs and the prognosis of patients with symptomatic coronary artery disease (CAD). Furthermore, we sought to investigate the influence of C5 SNPs on C5aR platelet surface expression and circulating C5a levels.Methods: C5 variants (rs25681, rs17611, rs17216529, rs12237774, rs41258306, and rs10985126) were analyzed in a consecutive cohort of 833 patients suffering from symptomatic coronary artery disease (CAD). Circulating C5a levels were determined in 116 patients whereas C5aR platelet surface expression was measured in 473 CAD patients. Endpoints included all-cause mortality, myocardial infarction (MI), and ischemic stroke (IS). Homozygous carriers (HC) of the minor allele (rs10985126) showed significantly higher all-cause mortality than major allele carriers. While we could not find significant associations between rs10985126 allele frequency and C5aR platelet surfazl ce expression, significantly elevated levels of circulating C5a were found in HC of the minor allele of the respective genotype. rs17216529 allele frequency correlated with the composite combined endpoint and bleeding events. However, since the number of HC of the minor allele of this genotype was low, we cannot draw a robust conclusion about the observed associations.Conclusion: In this study, we provide evidence for the prognostic relevance of rs10985126 in CAD patients. C5 rs10985126 may serve as a prognostic biomarker for risk stratification in high-risk CAD patients and consequently promote tailored therapies.Keywords: coronary artery disease, SNPs, complement C5, prognostic factors

Published
2021

4. Immunological evaluation of the new stable ultrasound contrast agent LK565: a phase one clinical trial

Author

Wild P, Sack U, Lehmann I, Polata S, Okorokow S, Maerz HK, Funke B, Geisler T, and Zotz RJ

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Ultrasound contrast agents (UCAs) allow the enhancement of vascular definition, thereby providing more diagnostic information. LK565 is a new second-generation UCA based on synthetic polymers of aspartic acid which is eliminated from the blood stream via phagocytosis. LK565 forms very stable air-filled microspheres and is capable of repeated passage through the pulmonary capillary bed after peripheral intravenous injection. This characteristic allows examination of the cardiac function or extracardiac vessel abnormalities up to 15 minutes. Methods A phase one clinical study was conducted on 15 healthy volunteers to identify the development of an undesirable immune response. Phagocytosis capacity, TNF-α secretion, and MHC class II upregulation of monocytes was monitored, as well as microsphere specific antibody development (IgM, IgG). Furthermore, the kinetics of the activation surface markers CD69, CD25, CD71, and CD11b on leukocytes were analyzed. Results Due to LK565-metabolism the administration of the UCA led to saturation of phagocytes which was reversible after 24 hrs. Compared to positive controls neither significant TNF-α elevation, neither MHC class II and activation surface markers upregulation, nor specific antibody development was detectable. Conclusion The administration of LK565 provides a comfortable duration of signal enhancement, esp. in echocardiography, without causing a major activation cascade or triggering an adaptive immune response. To minimize the risk of undesirable adverse events such as anaphylactoid reactions, immunological studies should be included in clinical trials for new UCAs. The use of LK565 as another new ultrasound contrast agent should be encouraged as a safe means to provide additional diagnostic information.

Published
2004
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8. Solid-state diffusion in amorphous zirconolite

Author

Yang, C., Zarkadoula, E., Dove, M. T., Todorov, I. T., Geisler, T., Brazhkin, V. V., and Trachenko, K.

Subjects
Condensed Matter - Materials Science
Abstract

We discuss how structural disorder and amorphization affects solid-state diffusion, and consider zirconolite as a currently important case study. By performing extensive molecular dynamics simulations, we disentangle the effects of amorphization and density, and show that a profound increase of solid-state diffusion takes place as a result of amorphization. Importantly, this can take place at the same density as in the crystal, representing an interesting general insight regarding solid-state diffusion. We find that decreasing the density in the amorphous system increases pre-factors of diffusion constants, but not decreasing the activation energy. We also find that atomic species in zirconolite are affected differently by amorphization and density change. Our microscopic insights are relevant for understanding how solid-state diffusion changes due to disorder and for building predictive models of operation of materials to be used to encapsulate nuclear waste.

Published
2015
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10. Apixaban for TreatmenT of embolIC stroke of Undetermined Source - ATTICUS randomized trial - explorative analysis of AF burden in the ATTICUS cohort

Author

Geisler, T, primary, Keller, T, additional, Martus, P, additional, Poli, K, additional, Kraft, A, additional, Hoffmann, F, additional, Hobohm, C, additional, Niehaus, L, additional, Baezner, H J, additional, Wachter, R, additional, Schreieck, J, additional, Gawaz, M, additional, Ziemann, U, additional, and Poli, S, additional

Published
2023
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11. Management of dyslipidaemia in patients with coronary heart disease: Results from the ESC-EORP EUROASPIRE V survey in 27 countries

Author

De Backer, G., Jankowski, P., Kotseva, K., Mirrakhimov, E., Reiner, Z., Rydén, L., Tokgözoğlu, L., Wood, D., De Bacquer, D., Abreu, A., Aguiar, C., Badariene, J., Bruthans, J., Castro Conde, A., Cifkova, R., Crowley, J., Davletov, K., Bacquer, D. De, De Smedt, D., De Sutter, J., Deckers, J.W., Dilic, M., Dolzhenko, M., Druais, H., Dzerve, V., Erglis, A., Fras, Z., Gaita, D., Gotcheva, N., Grobbee, D.E., Gyberg, V., Hasan Ali, H., Heuschmann, P., Hoes, A.W., Lalic, N., Lehto, S., Lovic, D., Maggioni, A.P., Mancas, S., Marques-Vidal, P., Mellbin, L., Miličić, D., Oganov, R., Pogosova, N., Reiner, Ž., Stagmo, M., Störk, S., Sundvall, J., Tsioufis, K., Vulic, D., Wood, D.A., Jennings, C., Adamska, A., Adamska, S., Tuomilehto, J., Schnell, O., Fiorucci, E., Glemot, M., Larras, F., Missiamenou, V., Maggioni, A., Taylor, C., Ferreira, T., Lemaitre, K., Raman, L., DeSmedt, D., Willems, A.M., De Pauw, M., Vervaet, P., Bollen, J., Dekimpe, E., Mommen, N., Van Genechten, G., Dendale, P., Bouvier, C.A., Chenu, P., Huyberechts, D., Persu, A., Begic, A., Durak Nalbantic, A., Dzubur, A., Hadzibegic, N., Iglica, A., Kapidjic, S., Osmanagic Bico, A., Resic, N., Sabanovic Bajramovic, N., Zvizdic, F., Kovacevic-Preradovic, T., Popovic-Pejicic, S., Djekic, D., Gnjatic, T., Knezevic, T., Kos, Lj, Stanetic, B., Topic, G., Georgiev, Borislav, Terziev, A., Vladimirov, G., Angelov, A., Kanazirev, B., Nikolaeva, S., Tonkova, D., Vetkova, M., Milicic, D., Bosnic, A., Dubravcic, M., Glavina, M., Mance, M., Pavasovic, S., Samardzic, J., Batinic, T., Crljenko, K., Delic-Brkljacic, D., Dula, K., Golubic, K., Klobucar, I., Kordic, K., Kos, N., Nedic, M., Olujic, D., Sedinic, V., Blazevic, T., Pasalic, A., Percic, M., Sikic, J., Cífková, R., Hašplová, K., Šulc, P., Wohlfahrt, P., Mayer, O., Jr., Cvíčela, M., Filipovský, J., Gelžinský, J., Hronová, M., Hasan-Ali, H., Bakery, S., Mosad, E., Hamed, H.B., Ibrahim, A., Elsharef, M.A., Kholef, E.F., Shehata, A., Youssef, M., Elhefny, E., Farid, H., Moustafa, T.M., Sobieh, M.S., Kabil, H., Abdelmordy, A., Kiljander, E., Kiljander, P., Koukkunen, H., Mustonen, J., Cremer, C., Frantz, S., Haupt, A., Hofmann, U., Ludwig, K., Melnyk, H., Noutsias, M., Karmann, W., Prondzinsky, R., Herdeg, C., Hövelborn, T., Daaboul, A., Geisler, T., Keller, T., Sauerbrunn, D., Walz-Ayed, M., Ertl, G., Leyh, R., Ehlert, T., Klocke, B., Krapp, J., Ludwig, T., Käs, J., Starke, C., Ungethüm, K., Wagner, M., Wiedmann, S., Tolis, P., Vogiatzi, G., Sanidas, E., Tsakalis, K., Kanakakis, J., Koutsoukis, A., Vasileiadis, K., Zarifis, J., Karvounis, C., Gibson, I., Houlihan, A., Kelly, C., O'Donnell, M., Bennati, M., Cosmi, F., Mariottoni, B., Morganti, M., Cherubini, A., Di Lenarda, A., Radini, D., Ramani, F., Francese, M.G., Gulizia, M.M., Pericone, D., Aigerim, K., Zholdin, B., Amirov, B., Assembekov, B., Chernokurova, E., Ibragimova, F., Kodasbayev, A., Markova, A., Asanbaev, A., Toktomamatov, U., Tursunbaev, M., Zakirov, U., Abilova, S., Arapova, R., Bektasheva, E., Esenbekova, J., Neronova, K., Baigaziev, K., Baitova, G., Zheenbekov, T., Andrejeva, T., Bajare, I., Kucika, G., Labuce, A., Putane, L., Stabulniece, M., Klavins, E., Sime, I., Gedvilaite, L., Pečiuraite, D., Sileikienė, V., Skiauteryte, E., Solovjova, S., Sidabraite, R., Briedis, K., Ceponiene, I., Jurenas, M., Kersulis, J., Martinkute, G., Vaitiekiene, A., Vasiljevaite, K., Veisaite, R., Plisienė, J., Šiurkaitė, V., Vaičiulis, Ž., Czarnecka, D., Kozieł, P., Podolec, P., Nessler, J., Gomuła, P., Mirek-Bryniarska, E., Bogacki, P., Wiśniewski, A., Pająk, A., Wolfshaut-Wolak, R., Bućko, J., Kamiński, K., Łapińska, M., Paniczko, M., Raczkowski, A., Sawicka, E., Stachurska, Z., Szpakowicz, M., Musiał, W., Dobrzycki, S., Bychowski, J., Kosior, D.A., Krzykwa, A., Setny, M., Rak, A., Gąsior, Z., Haberka, M., Szostak-Janiak, K., Finik, M., Liszka, J., Botelho, A., Cachulo, M., Sousa, J., Pais, A., Durazzo, A., Matos, D., Gouveia, R., Rodrigues, G., Strong, C., Guerreiro, R., Aguiar, J., Cruz, M., Daniel, P., Morais, L., Moreira, R., Rosa, S., Rodrigues, I., Selas, M., Apostu, A., Cosor, O., Gaita, L., Giurgiu, L., Hudrea, C., Maximov, D., Moldovan, B., Mosteoru, S., Pleava, R., Ionescu, M., Parepa, I., Arutyunov, A., Ausheva, A., Isakova, S., Karpova, A., Salbieva, A., Sokolova, O., Vasilevsky, A., Pozdnyakov, Y., Antropova, O., Borisova, L., Osipova, I., Aleksic, M., Crnokrak, B., Djokic, J., Hinic, S., Vukasin, T., Zdravkovic, M., Lalic, N.M., Jotic, A., Lalic, K., Lukic, L., Milicic, T., Macesic, M., Stanarcic Gajovic, J., Stoiljkovic, M., Djordjevic, D., Kostic, S., Tasic, I., Vukovic, A., Jug, B., Juhant, A., Krt, A., Kugonjič, U., Chipayo Gonzales, D., Gómez Barrado, J.J., Kounka, Z., Marcos Gómez, G., Mogollón Jiménez, M.V., Ortiz Cortés, C., Perez Espejo, P., Porras Ramos, Y., Colman, R., Delgado, J., Otero, E., Pérez, A., Fernández-Olmo, M.R., Torres-LLergo, J., Vasco, C., Barreñada, E., Botas, J., Campuzano, R., González, Y., Rodrigo, M., de Pablo, C., Velasco, E., Hernández, S., Lozano, C., González, P., Castro, A., Dalmau, R., Hernández, D., Irazusta, F.J., Vélez, A., Vindel, C., Gómez-Doblas, J.J., García Ruíz, V., Gómez, L., Gómez García, M, Jiménez-Navarro, M., Molina Ramos, A., Marzal, D., Martínez, G., Lavado, R., Vidal, A., Boström-Nilsson, V., Kjellström, B., Shahim, B., Smetana, S., Hansen, O., Stensgaard-Nake, E., Klijn, A.J., Mangus, T.J.P., Peters, R.J.G., Scholte op Reimer, W., Snaterse, M., Aydoğdu, S., Ç Erol, Otürk, S., Tulunay Kaya, C., Ahmetoğlu, Y., Ergene, O., Akdeniz, B., Çırgamış, D., Akkoyun H Kültürsay, S., Kayıkçıoğlu, M., Çatakoğlu, A.B., Çengel, A., Koçak, A.A., Ağırbaşlı, M.A., Açıksarı, G., Çekin, M.E., Kaya, E.B., Koçyiğit, D., Öngen, Z., Özmen, E., Sansoy, V., Kaya, A., Oktay, V., Temizhan, A., Ünal, S., İ Yakut, Kalkan, A.K., Bozkurt, E., Kasapkara, H.A., Faradzh, C., Hrubyak, L., Konoplianyk, L., Kozhuharyova, N., Lobach, L., Nesukai, V., Nudchenko, O., Simagina, T., Yakovenko, L., Azarenko, V., Potabashny, V., Bazylevych, A., Bazylevych, M., Kaminska, K., Panchenko, L., Shershnyova, O., Ovrakh, T., Serik, S., Kolesnik, T., Kosova, H., Hoye P Atkin, A., Fellowes, D., Lindsay, S., Atkinson, C., Kranilla, C., Vinod, M., Beerachee, Y., Bennett, C., Broome, M., Bwalya, A., Caygill, Lindsay, Dinning, L., Gillespie, A., Goodfellow, R., Guy, J., Idress, T., Mills, C., Morgan, C., Oustance, N., Singh, N., Yare, M., Jagoda, J.M., Bowyer, H., Christenssen, V., Groves, A., Jan, A., Riaz, A., Gill, M., Sewell, T.A., Gorog, D., Baker, M., De Sousa, P., Mazenenga, T., Porter, J., Haines, F., Peachey, T., Taaffe, J., Wells, K., Ripley, D.P., Forward, H., McKie, H., Pick, S.L., Thomas, H.E., Batin, P.D., Exley, D., Rank, T., Wright, J., Kardos, A., Sutherland, S.-B., Wren, L., Leeson, P., Barker, D., Moreby, B., Sawyer, J., Stirrup, J., Brunton, M., Brodison, A., Craig, J., Peters, S., Kaprielian, R., Bucaj, A., Mahay, K., Oblak, M., Gale, C., Pye, M., McGill, Y., Redfearn, H., Fearnley, M., De Backer, Guy, Jankowski, Piotr, Kotseva, Kornelia, Mirrakhimov, Erkin, Reiner, Željko, Rydén, Lars, Tokgözoğlu, Lale, Wood, David, and De Bacquer, Dirk

Published
2019
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12. Pharmacological targeting of ACKR3/CXCR7 enhances anticoagulant acylcarnitine levels in platelets and modulates thrombotic response to lipids

Author

Thomas, S, additional, Dittrich, K, additional, Fu, X, additional, Cebo, M, additional, Lackner, M, additional, Bouzabia, B, additional, Geisler, T, additional, Nürnberg, B, additional, Beer-Hammer, S, additional, Schäffeler, E, additional, Hofmann, U, additional, Schwab, M, additional, Haag, M, additional, Lämmerhofer, M, additional, and Chatterjee, M, additional

Published
2023
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15. Secondary prevention in diabetic and nondiabetic coronary heart disease patients: Insights from the German subset of the hospital arm of the EUROASPIRE IV and V surveys

Author

Ungethüm, K., primary, Wiedmann, S., additional, Wagner, M., additional, Leyh, R., additional, Ertl, G., additional, Frantz, S., additional, Geisler, T., additional, Karmann, W., additional, Prondzinsky, R., additional, Herdeg, C., additional, Noutsias, M., additional, Ludwig, T., additional, Käs, J., additional, Klocke, B., additional, Krapp, J., additional, Wood, D., additional, Kotseva, K., additional, Störk, S., additional, and Heuschmann, P. U., additional

Published
2022
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32. Studiendesign – Gesundheitsökonomische Evaluation einer Interventionsstudie zur Delirreduktion (TRADE)

Author

Pahmeier, K, additional, Denkinger, M, additional, Seufferlein, T, additional, Klaus, J, additional, Bauer, J, additional, Katus, H, additional, Bahrmann, A, additional, Geisler, T, additional, Muche, R, additional, Müller, M, additional, Suhr, R, additional, Frankenhauser-Mannuß, J, additional, Flagmeier, AL, additional, Dallmeier, D, additional, Leinert, C, additional, Wasem, J, additional, Biermann-Stallwitz, J, additional, and Neumann, A, additional

Published
2021
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33. Prevention of stroke in patients with chronic coronary syndromes or peripheral arterial disease

Author

Parker, W. A. E., Gorog, D. A., Geisler, T., Vilahur, G., Sibbing, D., Rocca, Bianca, Storey, R. F., Rocca B. (ORCID:0000-0001-8304-6423), Parker, W. A. E., Gorog, D. A., Geisler, T., Vilahur, G., Sibbing, D., Rocca, Bianca, Storey, R. F., and Rocca B. (ORCID:0000-0001-8304-6423)

Abstract

Stroke is a common and devastating condition caused by atherothrombosis, thromboembolism, or haemorrhage. Patients with chronic coronary syndromes (CCS) or peripheral artery disease (PAD) are at increased risk of stroke because of shared pathophysiological mechanisms and risk-factor profiles. A range of pharmacological and non-pharmacological strategies can help to reduce stroke risk in these groups. Antithrombotic therapy reduces the risk of major adverse cardiovascular events, including ischaemic stroke, but increases the incidence of haemorrhagic stroke. Nevertheless, the net clinical benefits mean antithrombotic therapy is recommended in those with CCS or symptomatic PAD. Whilst single antiplatelet therapy is recommended as chronic treatment, dual antiplatelet therapy should be considered for those with CCS with prior myocardial infarction at high ischaemic but low bleeding risk. Similarly, dual antithrombotic therapy with aspirin and very-low-dose rivaroxaban is an alternative in CCS, as well as in symptomatic PAD. Full-dose anticoagulation should always be considered in those with CCS/PAD and atrial fibrillation. Unless ischaemic risk is particularly high, antiplatelet therapy should not generally be added to full-dose anticoagulation. Optimization of blood pressure, low-density lipoprotein levels, glycaemic control, and lifestyle characteristics may also reduce stroke risk. Overall, a multifaceted approach is essential to best prevent stroke in patients with CCS/PAD.

Published
2021

35. Biomarkers of coagulation and fibrinolysis in acute myocardial infarction: a joint position paper of the Association for Acute Cardio Vascular Care and the European Society of Cardiology Working Group on Thrombosis

Author

Krychtiuk, KA, Speidl, WS, Giannitsis, E, Gigante, B, Gorog, DA, Jaffe, AS, Mair, J, Mockel, M, Mueller, C, Storey, RF, Vilahur, G, Wojta, J, Huber, K, Halvorsen, S, Geisler, T, Morais, J, Lindahl, B, and Thygesen, K

Subjects
AMI, Myocardial infarction, Fibrinolysis, Thrombosis, cardiovascular diseases, Biomarkers
Abstract

The formation of a thrombus in an epicardial artery may result in an acute myocardial infarction (AMI). Despite major advances in acute treatment using network approaches to allocate patients to timely reperfusion and optimal antithrombotic treatment, patients remain at high risk for thrombotic complications. Ongoing activation of the coagulation system as well as thrombin-mediated platelet activation may both play a crucial role in this context. Whether measurement of circulating biomarkers of coagulation and fibrinolysis could be useful for risk stratification in secondary prevention is currently not fully understood. In addition, measurement of such biomarkers could be helpful to identify thrombus formation as the leading mechanism for AMI. The introduction of biomarkers of myocardial injury such as high-sensitivity cardiac troponins made rule-out of AMI even more precise. However, elevated markers of myocardial injury cannot provide proof of a type 1 AMI, let alone thrombus formation. The combined measurement of markers of myocardial injury with biomarkers reflecting ongoing thrombus formation might be helpful for the fast and correct diagnosis of an atherothrombotic type 1 AMI. This position paper gives an overview of the current knowledge and possible role of biomarkers of coagulation and fibrinolysis for the diagnosis of AMI, risk stratification, and individualized treatment strategies in patients with AMI.

Published
2021

38. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

Author

Lincoff, A. Michael, Nicholls, Stephen J., Riesmeyer, Jeffrey S., Barter, Philip J., Brewer, H. Bryan, Fox, Keith A. A., Gibson, C. Michael, Granger, Christopher, Menon, Venu, Montalescot, Gilles, Rader, Daniel, Tall, Alan R., McErlean, Ellen, Wolski, Kathy, Ruotolo, Giacomo, Vangerow, Burkhard, Weerakkody, Govinda, Goodman, Shaun G., Conde, Diego, McGuire, Darren K., Nicolau, Jose C., Leiva-Pons, Jose L., Pesant, Yves, Li, Weimin, Kandath, David, Kouz, Simon, Tahirkheli, Naeem, Mason, Denise, Nissen, Steven E. Del Valle M, Finnell JB, Standley J, Poi K, Croaning J, Tong YC, Guerra JL, Guasparini G, Hubert C, Ardissino D, Betteridge J, Borghi C, Bruckert E, Chiang CE, Cinteza M, Dalby AJ, Erlinge D, Fernandez-Ortiz A, Ge J, Gottlieb S, Goudev A, Gratsiansky N, Huber K, Ilavská A, Jeong MH, Jukema JW, Katus H, Keltai M, Krum H, Nielsen H, Ogawa H, Ongen Z, Parkhomenko A, Raugaliene R, Renkin J, Rynkiewicz A, Steinhubl S, White H, Widimsky P, Zhu J, Armstrong P, Ridker P, Mahaffey K, Steg G, Wittes J, Bhargava A, Chenier M, Coleman C, Cremer P, Jellis C, Lahoud R, Lappe J, Min D, Monteleone P, Newton D, Stegman B, Senn T, Katzan I, Sharma J, Uchino K, Vora N, Brown K, Fabec D, Piper P, Preston S, Colombo T, Pagel-Langenickel I, Penev P, Maixing A, Crowley K, Sarkar S, Torosyan N, Castano L, Tran D, Dena V, Blain L, Keenan G, Slade K, Quinlan E, Edwards R, Ren H, Glenny J, Maffei L, Albisu Di Gennaro J, Caccavo A, Prado A, Colombo H, Luquez H, Lobo Marquez L, Hammett C, Blombery P, Colquhoun D, Amerena J, Howes L, Cooke D, Simpson R, Horowitz J, Sullivan D, Proietto J, Yeo W, Hirschl M, Hanusch U, Drexel H, Brodmann M, Wollaert B, De Wolf L, Delforge M, Vanwelden J, Peeters A, Siqueira Bodart J, Montenegro R, Franken M, Eliaschewitz F, Parvanova Z, Raev D, Mincheva V, Kichukov K, Stoyanov M, Apostolova E, Tzekova M, Dimov B, Lazov P, Devedzhiev T, Dion D, Poirier P, Lavoie JP, Lonn E, Shukla D, Chehayeb R, Nault P, Gaudet D, Tardif JC, Beaudry Y, Bakbak A, Wong B, St-Maurice F, Labonte R, Polasek P, Sweet M, Bhargava R, Nawaz S, Pandey S, Tishler S, Peterson S, O’Keefe D, Genest J, Syan R, Leiter L, Li H, Ma W, Ma C, Xu D, Li X, Hala T, Machova V, Smejkalova O, Vodnansky P, Reichert P, Velimsky T, Matuska J, Machkova M, Jerabek O, Kuchar J, Rasmussen T, Lindgren L, Alexandersen P, Bang L, Brønnum-Schou J, Valter I, Soots M, Lanno R, Rosenthal S, Cottin Y, Elbaz M, Lafitte S, Silvain J, Coste P, Rangé G, Gosse P, Morel O, Berrouschot J, Bourhaial H, Toursarkissian N, Appel KF, Rieker W, Stellbrink C, Münzel T, Geisler T, Kadel C, Giannitsis E, Trenk D, vom Dahl J, Dorsel T, Singer O, Schäufele T, Natour M, Ozaki R, Lau E, Chan K, Yeung V, Yu C, Lakatos F, Zólyomi S, Vangel S, Merkely B, Szakal I, Sipos A, Laszloczky A, Kis E, Szocs A, Szántai G, Faludi P, Kancz S, Oroszlan T, Hamoud S, Francis A, Chorin E, Leibowitz D, Kracoff O, Weisz G, Schiff E, Bitzur R, Hussein O, Di Lorenzo L, Visona A, Mos L, De Luca G, Salvioni A, Rubba P, Imberti D, Bucci M, Saku K, Sueyoshi A, Ohshima K, Kazatani Y, Shimizu M, Fujii K, Higa N, Kawamitsu K, Shimomura H, Hoshizaki H, Tashiro H, Baden M, Ueda O, Tanabe J, Momiyama Y, Hosokawa S, Takahashi N, Kimura K, Fujinaga H, Masutani M, Kuramochi T, Higashikata T, Ichikawa S, Yamagishi M, Sakota S, Sakuragi S, Suzuki M, Taguchi S, Nakamura T, Ozaki Y, Tsujita K, Yasuda S, Ando K, Fujimoto K, Tanabe K, Fukunaga M, Kavaliauskiene R, Motiejuniene L, Slapikas R, Jarasuniene D, De los Rios Ibarra M, Alcocer Gamba M, Nevarez Ruiz L, Fajardo-Campos P, Llamas Esperon G, Violante Ortiz R, Stobschinski de Alba C, Guizar Sanchez C, Guerra Lopez A, Montano E, Miracle S, Fanghanel G, Lenderink T, Troquay R, Van Leendert R, van Eck J, Hamer B, Ronner E, Karalis I, Lok D, Magro M, Westendorp I, Stroes E, De Melker E, Verhave G, Plomp J, Bronzwaer P, Wiersma J, Kooy A, Herrman JP, Imholz B, de Groot M, Devlin G, Elliott J, Benatar J, Harding S, Hart H, Young C, Mirek-Bryniarska E, Gniot J, Broncel M, Kozina M, Kus W, Sciborski R, Lesnik J, Kawka-Urbanek T, Krzyzanowski M, Okopien B, Wierzbicka K, Dyczek A, Ochean V, Copaci I, Matei C, Pruna C, Constantinescu M, Minescu B, Stamate C, Boldueva S, Markov V, Alexeeva N, Chizhov P, Supryadkina T, Petrochenkova N, Zrazhevsky K, Barbarash O, Gurevich V, Hranai M, Gergel V, Dzupina A, Uhliar R, Vinanska D, Fazekas F, Bugan W, Saaiman J, Nortje H, Theron H, Bernhardi D, Ramlachan P, Van-Zyl L, Basson M, Venter T, Kim D, Han S, Park G, Hwang K, Rhee M, Cho B, Jeong J, Hong B, Chang K, Garcia Puig J, Fuentes Jiménez F, Nieto Iglesias LJ, Pintó Sala X, Gamez JM, Sánchez Álvarez J, Hernandez García JM, Olsson A, Mooe T, Tengmark BO, Lindholm CJ, Hansen O, Tyden P, Moccetti T, Binder R, Ueng K, Lai W, Shyu K, Hsieh I, Sheu W, Chen J, Altunkeser B, Erkan A, Karpenko O, Kaydashev I, Yagensky A, Kovalenko V, Brunskill J, Barr C, Cecil J, Cahill T, A Gorog D, Bakhai A, Coulson W, Gorog D, Loftus I, Haddad T, Hotchkiss D, Isserman S, Janik M, Weinstein D, Wilson S, Butman S, Hearne S, Khan F, Nadar V, Zelman R, Benton R, Flores E, Kahn B, Soni A, Asbill B, Singal D, Dy J, Foucauld J, Crenshaw B, Rogers W, Aslam A, Lieber I, Shah P, Durr S, Spencer R, Mahal S, Cheng S, Abadier R, Gilmore R, Staniloae C, Miller G, Seals A, Jetty P, Mathis C, Henry S, Murray A, Felten W, Navas J, Gudipati R, Singh N, West S, Sabatino K, Crater T, Amin J, Dosh K, Earl J, Z Jafar M, Gelernt M, Kutner M, Salazar J, Krantzler J, El-Ahdab F, Lader E, Zakhary B, Miller S, Madder R, Khan T, Khan M, Collis W, Evans J, Prodafikas J, Panchal V, Cohen K, Weiss R, Dietrich D, Vogel C, Mascarenhas V, Seaworth J, Teklinski A, Davalos J, Dehning M, Herzog W, Snyder H, Talano J, Donahoe S, Hunter J, Sandoval J, Batchelor W, Brautigam D, Moriarty K, Siachos A, Kereiakes D, Traboulssi M, Arif I, Kosinski E, Quadrel M, DeHart D, Miller M, Poock J, Loh I, van Cleeff M, Georgeson S, Suryanarayana P, Cohn J, Schmedtje J, Lamas G, DeSantis J, Stahl L, Prashad R, Schuchard T, Schramm E, Rao V, Deen C, Soufer J, Gurbel P, Vazquez-Tanus J, Srivastava S, Ballantyne C, Lotun K, Younis L, Gupta D, Yeoman G, Zebrack J, Knutson T, Whitaker J, Appel M, Koren M, Muneer B, Fairlamb J, Aviles R, Kozlowski L, Rees A, Stephens M, Mays M, Downey H, Almassi H, Peichert D, Rocco M, French W, Bhatia P, Hoch J, Peart B, Carmichael P, Acheatel R, Vo A, Kirtane A, Bhagwat R, Gilchrist I, Labroo A, Pollock S, Bacon J, Karunaratne H, Moursi M, Doshi A, Sethi P, Treasure C, Marple R, Goodwin T, Zayas-Torres C, Loussararian A, Korn D, Paster R, Albirini A, Moretto T, Guarnieri T, White L, Kramer J, Shortal B, Maynard K, Raikhel M, Rohatgi A, Melucci M, Masri B, Krichmar P, Morris F, Canto J, Wali A, Comerota A, Ellison W, Degregorio M, Chandrika Parameswaran A, Goldscher D, George W, Mulkay A, Maynard R, Ziada K, Strain J, Hermiller J, Ennis B, Desai V, Al-Joundi B, Azocar J, Claudio J, Perez Vargas E, Loy J, Albert M, Chandler G, Maislos F, Graf R, Rama P, Studeny M, Gimple L, Pytlewski G, Simon H, Islam A, Dillon W, Shah S, Geohas C., Lincoff, Am, Nicholls, Sj, Riesmeyer, J, Barter, Pj, Brewer, Hb, Fox, Kaa, Gibson, Cm, Granger, C, Menon, V, Montalescot, G, Rader, D, Tall, Ar, Mcerlean, E, Wolski, K, Ruotolo, G, Vangerow, B, Weerakkody, G, Goodman, Sg, Conde, D, Mcguire, Dk, Nicolau, Jc, Leiva-Pons, Jl, Pesant, Y, Li, W, Kandath, D, Kouz, S, Tahirkheli, N, Mason, D, Nissen, Se, Del Valle, M, Finnell, Jb, Standley, J, Poi, K, Croaning, J, Tong, Yc, Guerra, Jl, Guasparini, G, Hubert, C, Ardissino, D, Betteridge, J, Borghi, C, Bruckert, E, Chiang, Ce, Cinteza, M, Dalby, Aj, Erlinge, D, Fernandez-Ortiz, A, Ge, J, Gottlieb, S, Goudev, A, Gratsiansky, N, Huber, K, Ilavská, A, Jeong, Mh, Jukema, Jw, Katus, H, Keltai, M, Krum, H, Nielsen, H, Ogawa, H, Ongen, Z, Parkhomenko, A, Raugaliene, R, Renkin, J, Rynkiewicz, A, Steinhubl, S, White, H, Widimsky, P, Zhu, J, Armstrong, P, Ridker, P, Mahaffey, K, Steg, G, Wittes, J, Bhargava, A, Chenier, M, Coleman, C, Cremer, P, Jellis, C, Lahoud, R, Lappe, J, Min, D, Monteleone, P, Newton, D, Stegman, B, Senn, T, Katzan, I, Sharma, J, Uchino, K, Vora, N, Brown, K, Fabec, D, Piper, P, Preston, S, Colombo, T, Pagel-Langenickel, I, Penev, P, Maixing, A, Crowley, K, Sarkar, S, Torosyan, N, Castano, L, Tran, D, Dena, V, Blain, L, Keenan, G, Slade, K, Quinlan, E, Edwards, R, Ren, H, Glenny, J, Maffei, L, Albisu Di Gennaro, J, Caccavo, A, Prado, A, Colombo, H, Luquez, H, Lobo Marquez, L, Hammett, C, Blombery, P, Colquhoun, D, Amerena, J, Howes, L, Cooke, D, Simpson, R, Horowitz, J, Sullivan, D, Proietto, J, Yeo, W, Hirschl, M, Hanusch, U, Drexel, H, Brodmann, M, Wollaert, B, De Wolf, L, Delforge, M, Vanwelden, J, Peeters, A, Siqueira Bodart, J, Montenegro, R, Franken, M, Eliaschewitz, F, Parvanova, Z, Raev, D, Mincheva, V, Kichukov, K, Stoyanov, M, Apostolova, E, Tzekova, M, Dimov, B, Lazov, P, Devedzhiev, T, Dion, D, Poirier, P, Lavoie, Jp, Lonn, E, Shukla, D, Chehayeb, R, Nault, P, Gaudet, D, Tardif, Jc, Beaudry, Y, Bakbak, A, Wong, B, St-Maurice, F, Labonte, R, Polasek, P, Sweet, M, Bhargava, R, Nawaz, S, Pandey, S, Tishler, S, Peterson, S, O’Keefe, D, Genest, J, Syan, R, Leiter, L, Li, H, Ma, W, Ma, C, Xu, D, Li, X, Hala, T, Machova, V, Smejkalova, O, Vodnansky, P, Reichert, P, Velimsky, T, Matuska, J, Machkova, M, Jerabek, O, Kuchar, J, Rasmussen, T, Lindgren, L, Alexandersen, P, Bang, L, Brønnum-Schou, J, Valter, I, Soots, M, Lanno, R, Rosenthal, S, Cottin, Y, Elbaz, M, Lafitte, S, Silvain, J, Coste, P, Rangé, G, Gosse, P, Morel, O, Berrouschot, J, Bourhaial, H, Toursarkissian, N, Appel, Kf, Rieker, W, Stellbrink, C, Münzel, T, Geisler, T, Kadel, C, Giannitsis, E, Trenk, D, vom Dahl, J, Dorsel, T, Singer, O, Schäufele, T, Natour, M, Ozaki, R, Lau, E, Chan, K, Yeung, V, Yu, C, Lakatos, F, Zólyomi, S, Vangel, S, Merkely, B, Szakal, I, Sipos, A, Laszloczky, A, Kis, E, Szocs, A, Szántai, G, Faludi, P, Kancz, S, Oroszlan, T, Hamoud, S, Francis, A, Chorin, E, Leibowitz, D, Kracoff, O, Weisz, G, Schiff, E, Bitzur, R, Hussein, O, Di Lorenzo, L, Visona, A, Mos, L, De Luca, G, Salvioni, A, Rubba, P, Imberti, D, Bucci, M, Saku, K, Sueyoshi, A, Ohshima, K, Kazatani, Y, Shimizu, M, Fujii, K, Higa, N, Kawamitsu, K, Shimomura, H, Hoshizaki, H, Tashiro, H, Baden, M, Ueda, O, Tanabe, J, Momiyama, Y, Hosokawa, S, Takahashi, N, Kimura, K, Fujinaga, H, Masutani, M, Kuramochi, T, Higashikata, T, Ichikawa, S, Yamagishi, M, Sakota, S, Sakuragi, S, Suzuki, M, Taguchi, S, Nakamura, T, Ozaki, Y, Tsujita, K, Yasuda, S, Ando, K, Fujimoto, K, Tanabe, K, Fukunaga, M, Kavaliauskiene, R, Motiejuniene, L, Slapikas, R, Jarasuniene, D, De los Rios Ibarra, M, Alcocer Gamba, M, Nevarez Ruiz, L, Fajardo-Campos, P, Llamas Esperon, G, Violante Ortiz, R, Stobschinski de Alba, C, Guizar Sanchez, C, Guerra Lopez, A, Montano, E, Miracle, S, Fanghanel, G, Lenderink, T, Troquay, R, Van Leendert, R, van Eck, J, Hamer, B, Ronner, E, Karalis, I, Lok, D, Magro, M, Westendorp, I, Stroes, E, De Melker, E, Verhave, G, Plomp, J, Bronzwaer, P, Wiersma, J, Kooy, A, Herrman, Jp, Imholz, B, de Groot, M, Devlin, G, Elliott, J, Benatar, J, Harding, S, Hart, H, C, Young, Mirek-Bryniarska, E, Gniot, J, Broncel, M, Kozina, M, Kus, W, Sciborski, R, Lesnik, J, Kawka-Urbanek, T, Krzyzanowski, M, Okopien, B, Wierzbicka, K, Dyczek, A, Ochean, V, Copaci, I, Matei, C, Pruna, C, Constantinescu, M, Minescu, B, Stamate, C, Boldueva, S, Markov, V, Alexeeva, N, Chizhov, P, Supryadkina, T, Petrochenkova, N, Zrazhevsky, K, Barbarash, O, Gurevich, V, Hranai, M, Gergel, V, Dzupina, A, Uhliar, R, Vinanska, D, Fazekas, F, Bugan, W, Saaiman, J, Nortje, H, Theron, H, Bernhardi, D, Ramlachan, P, Van-Zyl, L, Basson, M, Venter, T, Kim, D, Han, S, Park, G, Hwang, K, Rhee, M, Cho, B, Jeong, J, Hong, B, Chang, K, Garcia Puig, J, Fuentes Jiménez, F, Nieto Iglesias LJ, Pintó Sala, X, Gamez, Jm, Sánchez Álvarez, J, Hernandez García JM, Olsson, A, Mooe, T, Tengmark, Bo, Lindholm, Cj, Hansen, O, Tyden, P, Moccetti, T, Binder, R, Ueng, K, Lai, W, Shyu, K, Hsieh, I, Sheu, W, Chen, J, Altunkeser, B, Erkan, A, Karpenko, O, Kaydashev, I, Yagensky, A, Kovalenko, V, Brunskill, J, Barr, C, Cecil, J, Cahill, T, A Gorog D, Bakhai, A, Coulson, W, Gorog, D, Loftus, I, Haddad, T, Hotchkiss, D, Isserman, S, Janik, M, Weinstein, D, Wilson, S, Butman, S, Hearne, S, Khan, F, Nadar, V, Zelman, R, R, Benton, E, Flore, Kahn, B, Soni, A, Asbill, B, Singal, D, Dy, J, Foucauld, J, Crenshaw, B, Rogers, W, Aslam, A, Lieber, I, Shah, P, Durr, S, Spencer, R, Mahal, S, Cheng, S, Abadier, R, Gilmore, R, Staniloae, C, Miller, G, Seals, A, Jetty, P, Mathis, C, Henry, S, Murray, A, Felten, W, Navas, J, Gudipati, R, Singh, N, West, S, Sabatino, K, Crater, T, Amin, J, Dosh, K, Earl, J, Z Jafar M, Gelernt, M, Kutner, M, J, Salazar, Krantzler, J, El-Ahdab, F, Lader, E, Zakhary, B, Miller, S, Madder, R, Khan, T, Khan, M, Collis, W, Evans, J, Prodafikas, J, Panchal, V, Cohen, K, Weiss, R, Dietrich, D, Vogel, C, Mascarenhas, V, Seaworth, J, Teklinski, A, Davalos, J, Dehning, M, Herzog, W, Snyder, H, Talano, J, Donahoe, S, Hunter, J, Sandoval, J, Batchelor, W, Brautigam, D, Moriarty, K, Siachos, A, Kereiakes, D, Traboulssi, M, Arif, I, Kosinski, E, Quadrel, M, Dehart, D, Miller, M, Poock, J, Loh, I, van Cleeff, M, Georgeson, S, Suryanarayana, P, Cohn, J, Schmedtje, J, Lamas, G, Desantis, J, Stahl, L, Prashad, R, Schuchard, T, Schramm, E, Rao, V, Deen, C, Soufer, J, Gurbel, P, Vazquez-Tanus, J, Srivastava, S, Ballantyne, C, Lotun, K, Younis, L, Gupta, D, Yeoman, G, Zebrack, J, Knutson, T, Whitaker, J, Appel, M, Koren, M, Muneer, B, Fairlamb, J, Aviles, R, Kozlowski, L, Rees, A, Stephens, M, Mays, M, Downey, H, Almassi, H, Peichert, D, Rocco, M, French, W, Bhatia, P, Hoch, J, Peart, B, Carmichael, P, Acheatel, R, Vo, A, Kirtane, A, Bhagwat, R, Gilchrist, I, Labroo, A, Pollock, S, Bacon, J, Karunaratne, H, Moursi, M, Doshi, A, Sethi, P, Treasure, C, Marple, R, Goodwin, T, Zayas-Torres, C, Loussararian, A, Korn, D, Paster, R, Albirini, A, Moretto, T, Guarnieri, T, White, L, Kramer, J, Shortal, B, Maynard, K, Raikhel, M, Rohatgi, A, Melucci, M, Masri, B, Krichmar, P, Morris, F, Canto, J, Wali, A, Comerota, A, Ellison, W, Degregorio, M, Chandrika Parameswaran, A, Goldscher, D, George, W, Mulkay, A, Maynard, R, Ziada, K, Strain, J, Hermiller, J, Ennis, B, Desai, V, Al-Joundi, B, Azocar, J, Claudio, J, Perez Vargas, E, Loy, J, Albert, M, Chandler, G, Maislos, F, Graf, R, Rama, P, Studeny, M, Gimple, L, Pytlewski, G, Simon, H, Islam, A, Dillon, W, Shah, S, Geohas, C., Lincoff, A. Michael, Nicholls, Stephen J., Riesmeyer, Jeffrey S., Barter, Philip J., Brewer, H. Bryan, Fox, Keith A. A., Gibson, C. Michael, Granger, Christopher, Menon, Venu, Montalescot, Gille, Rader, Daniel, Tall, Alan R., Mcerlean, Ellen, Wolski, Kathy, Ruotolo, Giacomo, Vangerow, Burkhard, Weerakkody, Govinda, Goodman, Shaun G., Conde, Diego, Mcguire, Darren K., Nicolau, Jose C., Leiva-Pons, Jose L., Pesant, Yve, Li, Weimin, Kandath, David, Kouz, Simon, Tahirkheli, Naeem, Mason, Denise, Nissen, Steven E., Del Valle M, Young, C, Nieto Iglesias, Lj, Hernandez García, Jm, A Gorog, D, Benton, R, Flores, E, Z Jafar, M, and Salazar, J

Subjects
Male, 0301 basic medicine, Cardiovascular Outcome, Cholesterol Ester Transfer Protein, Myocardial Ischemia, 030204 cardiovascular system & hematology, Coronary artery disease, cholesteryl ester transfer protein inhibitor, Benzodiazepines, chemistry.chemical_compound, 0302 clinical medicine, Cardiovascular Disease, Anticholesteremic Agent, Intracranial Arteriosclerosi, Treatment Failure, Evacetrapib, Peripheral Vascular Diseases, Benzodiazepine, biology, Medicine (all), Anticholesteremic Agents, Diabetes Mellitu, General Medicine, Middle Aged, Intracranial Arteriosclerosis, High-Risk Vascular Disease, Editorial, Cardiovascular Diseases, Cardiology, Female, lipids (amino acids, peptides, and proteins), Human, Risk, medicine.medical_specialty, Acute coronary syndrome, 03 medical and health sciences, Double-Blind Method, Internal medicine, Diabetes mellitus, Cholesterylester transfer protein, Diabetes Mellitus, Journal Article, medicine, Humans, Aged, Cholesterol, Vascular disease, business.industry, Cholesterol, HDL, Biomarker, Cholesterol, LDL, medicine.disease, Cholesterol Ester Transfer Proteins, Surgery, 030104 developmental biology, Peripheral Vascular Disease, chemistry, biology.protein, business, Biomarkers, Lipoprotein
Abstract

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).

Published
2017

42. Studiendesign – Gesundheitsökonomische Evaluation einer Intervention zur Delirreduktion (TRADE)

Author

Pahmeier, K, Denkinger, M, Seufferlein, T, Klaus, J, Bauer, J, Katus, H, Bahrmann, A, Geisler, T, Muche, R, Müller, M, Suhr, R, Frankenhauser-Mannuß, J, Flagmeier, AL, Dallmeier, D, Leinert, C, Wasem, J, and Neumann, A

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund und Stand (inter)nationaler Forschung: Eine Umgebungsveränderung kann bei geriatrischen Patienten mit einer Verschlechterung der kognitiven Funktion assoziiert sein. Dies konnte bereits für mehrere Raumwechsel innerhalb einer Institution gezeigt werden. Eine schwierige (Re-)Orientierung[zum vollständigen Text gelangen Sie über die oben angegebene URL], 19. Deutscher Kongress für Versorgungsforschung (DKVF)

Published
2020
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43. Genomewide Association Study of Platelet Reactivity and Cardiovascular Response in Patients Treated With Clopidogrel: A Study by the International Clopidogrel Pharmacogenomics Consortium

Author

Verma, S.S. Bergmeijer, T.O. Gong, L. Reny, J.-L. Lewis, J.P. Mitchell, B.D. Alexopoulos, D. Aradi, D. Altman, R.B. Bliden, K. Bradford, Y. Campo, G. Chang, K. Cleator, J.H. Déry, J.-P. Dridi, N.P. Fernandez-Cadenas, I. Fontana, P. Gawaz, M. Geisler, T. Gensini, G.F. Giusti, B. Gurbel, P.A. Hochholzer, W. Holmvang, L. Kim, E.-Y. Kim, H.-S. Marcucci, R. Montaner, J. Backman, J.D. Pakyz, R.E. Roden, D.M. Schaeffeler, E. Schwab, M. Shin, J.G. Siller-Matula, J.M. ten Berg, J.M. Trenk, D. Valgimigli, M. Wallace, J. Wen, M.-S. Kubo, M. Lee, M.T.M. Whaley, R. Winter, S. Klein, T.E. Shuldiner, A.R. Ritchie, M.D. for the ICPC Investigators

Subjects
cardiovascular diseases
Abstract

Antiplatelet response to clopidogrel shows wide variation, and poor response is correlated with adverse clinical outcomes. CYP2C19 loss-of-function alleles play an important role in this response, but account for only a small proportion of variability in response to clopidogrel. An aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify other genetic determinants of clopidogrel pharmacodynamics and clinical response. A genomewide association study (GWAS) was performed using DNA from 2,750 European ancestry individuals, using adenosine diphosphate-induced platelet reactivity and major cardiovascular and cerebrovascular events as outcome parameters. GWAS for platelet reactivity revealed a strong signal for CYP2C19*2 (P value = 1.67e−33). After correction for CYP2C19*2 no other single-nucleotide polymorphism reached genomewide significance. GWAS for a combined clinical end point of cardiovascular death, myocardial infarction, or stroke (5.0% event rate), or a combined end point of cardiovascular death or myocardial infarction (4.7% event rate) showed no significant results, although in coronary artery disease, percutaneous coronary intervention, and acute coronary syndrome subgroups, mutations in SCOS5P1, CDC42BPA, and CTRAC1 showed genomewide significance (lowest P values: 1.07e−09, 4.53e−08, and 2.60e−10, respectively). CYP2C19*2 is the strongest genetic determinant of on-clopidogrel platelet reactivity. We identified three novel associations in clinical outcome subgroups, suggestive for each of these outcomes. © 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

Published
2020

44. Studie TRADE (TRAnsport und DElir von älteren Menschen) - Entwicklung einer komplexen Intervention zur Delirprävention und -reduktion bei Ortswechsel von älteren Menschen im Akutkrankenhaus

Author

Denninger, NE, Dallmeier, D, Carmine, M, Bahrmann, A, Benzinger, P, Braisch, U, Eggert, S, Geisler, T, Klaus, J, Neumann, A, Denkinger, M, Müller, M, Denninger, NE, Dallmeier, D, Carmine, M, Bahrmann, A, Benzinger, P, Braisch, U, Eggert, S, Geisler, T, Klaus, J, Neumann, A, Denkinger, M, and Müller, M

Published
2020

45. Usefulness of the updated logistic clinical SYNTAX score after percutaneous coronary intervention in patients with prior coronary artery bypass graft surgery: Insights from the GLOBAL LEADERS trial

Author

Hara, H. (Hironori), Kogame, N. (Norihiro), Takahashi, K. (Kuniaki), Modolo, R. (Rodrigo), Chichareon, P. (Ply), Tomaniak, M. (Mariusz), Ono, M. (Masafumi), Kawashima, H. (Hideyuki), Gao, C. (Chao), Wang, R. (Rutao), Valkov, V.D. (Veselin D.), vom Dahl, J. (Jürgen), Steinwender, C. (Clemens), Geisler, T. (Tobias), Lemos Neto, P.A. (Pedro Alves), Macaya Miguel, C. (Carlos), Garg, S.A. (Scot), Jüni, P. (Peter), Hamm, C. (Christian), Steg, P.G. (Philippe Gabriel), Valgimigli, M. (Marco), Vranckx, P. (Pascal), Windecker, S.W. (Stephan), Farooq, V. (Vasim), Onuma, Y. (Yoshinobu), Serruys, P.W.J.C. (Patrick), Hara, H. (Hironori), Kogame, N. (Norihiro), Takahashi, K. (Kuniaki), Modolo, R. (Rodrigo), Chichareon, P. (Ply), Tomaniak, M. (Mariusz), Ono, M. (Masafumi), Kawashima, H. (Hideyuki), Gao, C. (Chao), Wang, R. (Rutao), Valkov, V.D. (Veselin D.), vom Dahl, J. (Jürgen), Steinwender, C. (Clemens), Geisler, T. (Tobias), Lemos Neto, P.A. (Pedro Alves), Macaya Miguel, C. (Carlos), Garg, S.A. (Scot), Jüni, P. (Peter), Hamm, C. (Christian), Steg, P.G. (Philippe Gabriel), Valgimigli, M. (Marco), Vranckx, P. (Pascal), Windecker, S.W. (Stephan), Farooq, V. (Vasim), Onuma, Y. (Yoshinobu), and Serruys, P.W.J.C. (Patrick)

Abstract

Objectives: We aimed to investigate the prognostic utility of the anatomical CABG SYNTAX and logistic clinical SYNTAX scores for mortality after percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass grafts (CABG). Background: The anatomical SYNTAX score evaluated the anatomical complexity of coronary artery disease and helped predict the prognosis of patients undergoing PCI. The anatomical CABG SYNTAX score was derived from the anatomical SYNTAX score in patients with prior CABG, whilst the logistic clinical SYNTAX score was developed by incorporating clinical factors into the anatomical SYNTAX score. Methods: We calculated the anatomical CABG SYNTAX score and logistic clinical SYNTAX score in 205 patients in the GLOBAL LEADERS trial. The predictive abilities of these scores for 2-year all-cause mortality were evaluated. Results: Using the median scores as categorical thresholds between low and high score groups, the logistic clinical SYNTAX score was able to discriminate the risk of 2-year mortality, unlike the anatomical CABG SYNTAX score. The logistic clinical SYNTAX was significantly better at predicting 2-year mortality, compared to the anatomical CABG SYNTAX score, as evidenced by AUC values in receiver-operating characteristic curve analysis (0.806 vs. 0.582, p <.001) and integrated discrimination improvement (0.121, p <.001). Conclusions: The logistic clinical SYNTAX score was superior to the anatomical CABG SYNTAX score in predicting 2-year mortality.

Published
2020
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46. Fluoridation of a lizard bone embedded in Dominican amber suggests open-system behavior

Author

Jonas Barthel, H., Fougerouse, Denis, Geisler, T., Rust, J., Jonas Barthel, H., Fougerouse, Denis, Geisler, T., and Rust, J.

Abstract

Vertebrate fossils embedded in amber represent a particularly valuable paleobiological record as amber is supposed to be a barrier to the environment, precluding significant alteration of the animals’ body over geological time. The mode and processes of amber preservation are still under debate, and it is questionable to what extent original material may be preserved. Due to their high value, vertebrates in amber have never been examined with analytical methods, which means that the composition of bone tissue in amber is unknown. Here, we report our results of a study on a left forelimb from a fossil Anolis sp. indet. (Squamata) that was fully embedded in Miocene Dominican amber. Our results show a transformation of the bioapatite to fluorapatite associated with a severe alteration of the collagen phase and the formation of an unidentified carbonate. These findings argue for a poor survival potential of macromolecules in Dominican amber fossils.

Published
2020

47. Usefulness of the updated logistic clinical SYNTAX score after percutaneous coronary intervention in patients with prior coronary artery bypass graft surgery: Insights from the GLOBAL LEADERS trial

Author

Hara, H, Kogame, N, Takahashi, K, Modolo, R, Chichareon, P, Tomaniak, Mariusz, Ono, M, Kawashima, H, Gao, C, Wang, R, Valkov, VD, Dahl, J, Steinwender, C, Geisler, T, Lemos Neto, PA, Macaya Miguel, C, Garg, S, Jüni, P, Hamm, C, Steg, PG, Valgimigli, M, Vranckx, P, Windecker, S, Farooq, V, Onuma, Y, Serruys, PWJC, Hara, H, Kogame, N, Takahashi, K, Modolo, R, Chichareon, P, Tomaniak, Mariusz, Ono, M, Kawashima, H, Gao, C, Wang, R, Valkov, VD, Dahl, J, Steinwender, C, Geisler, T, Lemos Neto, PA, Macaya Miguel, C, Garg, S, Jüni, P, Hamm, C, Steg, PG, Valgimigli, M, Vranckx, P, Windecker, S, Farooq, V, Onuma, Y, and Serruys, PWJC

Published
2020

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