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5. Ticagrelor for Secondary Prevention of Atherothrombotic Events in Patients With Multivessel Coronary Disease

Author

Bansilal, Sameer, Bonaca, Marc P., Cornel, Jan H., Storey, Robert F., Bhatt, Deepak L., Steg, Ph. Gabriel, Im, Kyungah, Murphy, Sabina A., Angiolillo, Dominick J., Kiss, Robert G., Parkhomenko, Alexander N., Lopez-Sendon, Jose, Isaza, Daniel, Goudev, Assen, Kontny, Frederic, Held, Peter, Jensen, Eva C., Braunwald, Eugene, Sabatine, Marc S., and Oude Ophuis, A.J.

Published
2018
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7. C-X-C LIGAND 16 IN UNDIFFERENTIATED CHEST PAIN PATIENTS

Author

Andersen, Thomas, primary, Ueland, Thor, additional, Nilsen, Dennis W.T., additional, Staines, Harry, additional, Aukrust, Pal, additional, Grundt, Heidi, additional, Pönitz, Volker, additional, Brügger-Andersen, Trygve, additional, and Kontny, Frederic, additional

Published
2023
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8. Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 year follow-up of a prospective, randomised, multicentre study

Author

Wallentin, Lars, Lindhagen, Lars, Ärnström, Elisabet, Husted, Steen, Janzon, Magnus, Johnsen, Søren Paaske, Kontny, Frederic, Kempf, Tibor, Levin, Lars-Åke, Lindahl, Bertil, Stridsberg, Mats, Ståhle, Elisabeth, Venge, Per, Wollert, Kai C, Swahn, Eva, and Lagerqvist, Bo

Published
2016
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10. The Effect of Protease-Activated Receptor-1 (PAR-1) Inhibition on Endothelial-Related Biomarkers in Patients with Coronary Artery Disease

Author

Nilsen, Dennis W. T., additional, Røysland, Michelle, additional, Ueland, Thor, additional, Aukrust, Pål, additional, Michelsen, Annika E., additional, Staines, Harry, additional, Barvik, Ståle, additional, Kontny, Frederic, additional, Nordrehaug, Jan Erik, additional, and Bonarjee, Vernon V. S., additional

Published
2022
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15. Efficacy and safety of ticagrelor for long-term secondary prevention of atherothrombotic events in relation to renal function: insights from the PEGASUS-TIMI 54 trial

Author

Magnani, Giulia, Storey, Robert F., Steg, Gabriel, Bhatt, Deepak L., Cohen, Marc, Kuder, Julia, Im, Kyungah, Aylward, Philip, Ardissino, Diego, Isaza, Daniel, Parkhomenko, Alexander, Goudev, Assen R., Dellborg, Mikael, Kontny, Frederic, Corbalan, Ramon, Medina, Felix, Jensen, Eva C., Held, Peter, Braunwald, Eugene, Sabatine, Marc S., and Bonaca, Marc P.

Published
2016
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16. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study

Author

Cannon, Christopher P, Harrington, Robert A, James, Stefan, Ardissino, Diego, Becker, Richard C, Emanuelsson, Håkan, Husted, Steen, Katus, Hugo, Keltai, Matyas, Khurmi, Nardev S, Kontny, Frederic, Lewis, Basil S, Steg, Philippe Gabriel, Storey, Robert F, Wojdyla, Daniel, and Wallentin, Lars

Published
2010
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18. Pentraxin-3 vs C-reactive protein and other prognostic biomarkers in acute coronary syndrome : A substudy of the Platelet Inhibition and Patients Outcomes (PLATO) trial

Author

Kontny, Frederic, Andersen, Thomas, Ueland, Thor, Åkerblom, Axel, Ghukasyan Lakic, Tatevik, Michelsen, Annika E., Aukrust, Pål, Bertilsson, Maria, Becker, Richard C., Himmelmann, Anders, James, Stefan K., Siegbahn, Agneta, Storey, Robert F., Wallentin, Lars, Kontny, Frederic, Andersen, Thomas, Ueland, Thor, Åkerblom, Axel, Ghukasyan Lakic, Tatevik, Michelsen, Annika E., Aukrust, Pål, Bertilsson, Maria, Becker, Richard C., Himmelmann, Anders, James, Stefan K., Siegbahn, Agneta, Storey, Robert F., and Wallentin, Lars

Abstract

AIMS: We investigated the dynamics, associations with patient characteristics, other biomarkers, and clinical outcomes of pentraxin 3 in acute coronary syndrome. METHODS AND RESULTS: In multivariate analyses, pentraxin 3 measured in 5154 patients randomised in the Platelet Inhibition and Patients Outcomes (PLATO) trial (NCT00391872) was compared with leukocytes, high-sensitivity C-reactive protein, interleukin-6, cystatin C, N-terminal prohormone brain natriuretic peptide, high-sensitivity troponin T and growth differentiation factor 15 concerning prediction of clinical outcome. Pentraxin 3 peaked earlier than high-sensitivity C-reactive protein and was more strongly correlated with N-terminal prohormone brain natriuretic peptide and high-sensitivity troponin T than with high-sensitivity C-reactive protein. The frequency of cardiovascular death, spontaneous myocardial infarction or stroke by quartiles of pentraxin 3 at admission was 6.1%, 7.3%, 9.7% and 10.7%, respectively ( p<0.0001). The hazard ratio per 50% increase of pentraxin 3 was 1.13 (95% confidence interval: 1.07-1.19), p<0.0001. This association remained significant after stepwise adjustments for leukocytes/high-sensitivity C-reactive protein (1.09 (1.02-1.15)), p=0.009, interleukin-6 (1.07 (1.01-1.14)), p=0.026, and cystatin C (1.07 (1.00-1.13)), p=0.044, but not after adjustment for N-terminal prohormone brain natriuretic peptide, high-sensitivity troponin T and growth differentiation factor 15. Admission pentraxin 3 was also associated with several of the individual endpoint components (cardiovascular death/spontaneous myocardial infarction; p=0.008, cardiovascular death; p=0.026, and spontaneous myocardial infarction; p=0.017), but not with stroke. Pentraxin 3 measured in the chronic phase (i.e. at one month) was still predictive of the composite endpoint in univariate analysis (1.12 (1.04-1.20) per 50% increase) p=0.0024, but not after adjustment for the other biomarkers. CONCLUSION: Admission

Published
2020
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19. Legumain in Acute Coronary Syndromes : A Substudy of the PLATO (Platelet Inhibition and Patient Outcomes) Trial

Author

Gregersen, Ida, Michelsen, Annika E., Lunde, Ngoc Nguyen, Åkerblom, Axel, Ghukasyan, Tatevik, Skjelland, Mona, Skagen, Karolina Ryeng, Becker, Richard C., Lindbäck, Johan, Himmelmann, Anders, Solberg, Rigmor, Johansen, Harald T., James, Stefan, Siegbahn, Agneta, Storey, Robert F., Kontny, Frederic, Aukrust, Pal, Ueland, Thor, Wallentin, Lars, Halvorsen, Bente, Gregersen, Ida, Michelsen, Annika E., Lunde, Ngoc Nguyen, Åkerblom, Axel, Ghukasyan, Tatevik, Skjelland, Mona, Skagen, Karolina Ryeng, Becker, Richard C., Lindbäck, Johan, Himmelmann, Anders, Solberg, Rigmor, Johansen, Harald T., James, Stefan, Siegbahn, Agneta, Storey, Robert F., Kontny, Frederic, Aukrust, Pal, Ueland, Thor, Wallentin, Lars, and Halvorsen, Bente

Abstract

BACKGROUND: The cysteine protease legumain is increased in patients with atherosclerosis, but its causal role in atherogenesis and cardiovascular disease is still unclear. The aim of the study was to investigate the association of legumain with clinical outcome in a large cohort of patients with acute coronary syndrome. METHODS AND RESULTS : Serum levels of legumain were analyzed in 4883 patients with acute coronary syndrome from a substudy of the PLATO (Platelet Inhibition and Patient Outcomes) trial. Levels were analyzed at admission and after 1 month follow-up. Associations between legumain and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and its individual components were assessed by multivariable Cox regression analyses. At baseline, a 50% increase in legumain level was associated with a hazard ratio (HR) of 1.13 (95% CI, 1.04-1.21),P=0.0018, for the primary composite end point, adjusted for randomized treatment. The association remained significant after adjustment for important clinical and demographic variables (HR, 1.10; 95% CI, 1.02-1.19;P=0.013) but not in the fully adjusted model. Legumain levels at 1 month were not associated with the composite end point but were negatively associated with stroke (HR, 0.62; 95% CI, 0.44-0.88;P=0.0069), including in the fully adjusted model (HR, 0.57; 95% CI, 0.37-0.88;P=0.0114). CONCLUSIONS: Baseline legumain was associated with the primary outcome in patients with acute coronary syndrome, but not in the fully adjusted model. The association between high levels of legumain at 1 month and decreased occurrence of stroke could be of interest from a mechanistic point of view, illustrating the potential dual role of legumain during atherogenesis and acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00391872.

Published
2020
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20. Legumain in Acute Coronary Syndromes: A Substudy of the PLATO (Platelet Inhibition and Patient Outcomes) Trial

Author

Gregersen, Ida, primary, Michelsen, Annika E., additional, Lunde, Ngoc Nguyen, additional, Åkerblom, Axel, additional, Lakic, Tatevik G., additional, Skjelland, Mona, additional, Ryeng Skagen, Karolina, additional, Becker, Richard C., additional, Lindbäck, Johan, additional, Himmelmann, Anders, additional, Solberg, Rigmor, additional, Johansen, Harald T., additional, James, Stefan K., additional, Siegbahn, Agneta, additional, Storey, Robert F., additional, Kontny, Frederic, additional, Aukrust, Pål, additional, Ueland, Thor, additional, Wallentin, Lars, additional, and Halvorsen, Bente, additional

Published
2020
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23. Long-term ticagrelor for secondary prevention in patients with prior myocardial infarction and no history of coronary stenting: insights from PEGASUS-TIMI 54

Author

Furtado, Remo H M, primary, Nicolau, Jose C, additional, Magnani, Giulia, additional, Im, Kyungah, additional, Bhatt, Deepak L, additional, Storey, Robert F, additional, Steg, P Gabriel, additional, Spinar, Jindrich, additional, Budaj, Andrzej, additional, Kontny, Frederic, additional, Corbalan, Ramon, additional, Kiss, Robert G, additional, Abola, Maria Teresa, additional, Johanson, Per, additional, Jensen, Eva C, additional, Braunwald, Eugene, additional, Sabatine, Marc S, additional, and Bonaca, Marc P, additional

Published
2019
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24. Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y 12 Receptor Antagonist Effects in Patients With Acute Coronary Syndromes: Insights From the PLATO Trial

Author

Franchi, Francesco, James, Stefan, Ghukasyan, Tatevik, Budaj, Andrzej J., Cornel, Jan H., Katus, Hugo A., Keltai, Matyas, Kontny, Frederic, Lewis, Basil S., Storey, Robert F., Himmelmann, Anders, Wallentin, Lars, Angiolillo, Dominick J., Parkhomenko, Alexander Nikolaevich, Oto, Ali, Skene, Allan, Budaj, Andrzej, Freij, Anneli, Santoso, Anwar, Armando, A, Meier, Bernhard, Yu, Cheuk Man, Cannon, Christopher P., Zambahari, Dato Seri Robaayah, Wu, Delon Wu, Ardissino, Diego, Raev, Dimitar, Kremastinos, Dimitrios, Weaver, Douglas, Paolasso, Ernesto, Giannitsis, Evangelos, Verheugt, Freek, Maurer, Gerald, Katus, Hugo, Emanuelsson, Hakan, Horrow, Jay, Bassand, Jean-Pierre, Spinar, Jindrich, Morais, Joao, Lopez Sendon, Jose, Nicolau, Jose, Seung, Ki-Bae, Teik, Lim Soo, Heras, Magda, Claeys, Marc J., Sabatine, Marc, Vintila, Marius, Ruda, Mikhail, Thorsen, Mona, Kleiman, Neil, Babilonia, Noe, Commerford, Patrick, Gurbel, Paul, Aylward, Phil, Steg, Philippe Gabriel, Theroux, Pierre, Sritara, Piyamitr, Pais, Prem, Becker, Richard, Lassila, Riitta, Harrington, Robert A., Gao, Runlin, Husted, Steen, Duris, Tibor, Chapichadze, Zaza, HUS Comprehensive Cancer Center, University Management, Department of Oncology, and PLATO Investigators

Subjects
Male, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Comorbidity, 030204 cardiovascular system & hematology, urologic and male genital diseases, FUNCTION PROFILES, RESPONSIVENESS, Electrocardiography, 0302 clinical medicine, Risk Factors, Coronary Heart Disease, ARTERY-DISEASE, Medicine, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, Myocardial infarction, Stroke, Original Research, Kardiologi, Absolute risk reduction, Diabetes, Type 2, DUAL ANTIPLATELET THERAPY, Middle Aged, Prognosis, Clopidogrel, female genital diseases and pregnancy complications, 3. Good health, Survival Rate, diabetes mellitus, Female, Cardiology and Cardiovascular Medicine, Ticagrelor, medicine.drug, Platelets, RENAL-FUNCTION, medicine.medical_specialty, Acute coronary syndrome, ANTITHROMBOTIC THERAPY, INHIBITION, acute coronary syndrome, ticagrelor, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Humans, Renal Insufficiency, Chronic, Aged, Retrospective Studies, Pharmacology, clopidogrel, Dose-Response Relationship, Drug, business.industry, Thrombosis, medicine.disease, United States, REACTIVITY, 3121 General medicine, internal medicine and other clinical medicine, Purinergic P2Y Receptor Antagonists, Human medicine, business, Acute Coronary Syndromes, Platelet Aggregation Inhibitors, chronic kidney disease, Follow-Up Studies, Kidney disease
Abstract

Background There are limited data on how the combination of diabetes mellitus ( DM ) and chronic kidney disease ( CKD ) affects cardiovascular outcomes as well as response to different P2Y 12 receptor antagonists, which represented the aim of the present investigation. Methods and Results In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM +/ CKD + (n=1058), DM +/ CKD − (n=2748), DM −/ CKD + (n=2160), and DM −/ CKD − (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM +/ CKD + patients had a higher incidence of the primary end point compared with DM −/ CKD − patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88–2.63; P DM +/ CKD − and DM −/ CKD + had an intermediate risk profile. The same trend was shown for the individual components of the primary end point and for major bleeding. Compared with clopidogrel, ticagrelor reduced the incidence of the primary end point consistently across subgroups ( P ‐interaction=0.264), but with an increased absolute risk reduction in DM +/ CKD +. The effects on major bleeding were also consistent across subgroups ( P ‐interaction=0.288). Conclusions In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD , with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD . Clinical Trial Registration URL : http://www.clinicatrials.gov . Unique identifier: NCT 00391872.

Published
2019

25. Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study

Author

Bhatt, Deepak L., Fox, Kim, Harrington, Robert A., Leiter, Lawrence A., Mehta, Shamir R., Simon, Tabassome, Andersson, Marielle, Himmelmann, Anders, Ridderstrale, Wilhelm, Held, Claes, Steg, Philippe Gabriel, Steg, Gabriel, Diaz, Rafael, Amerena, John, Huber, Kurt, Sinnaeve, Peter, Nicolau, Jose Carlos, Kerr Saraiva, Jose Francisco, Petrov, Ivo, Corbalan, Ramon, Ge, Junbo, Zhao, Qiang, Botero, Rodrigo, Widimsky, Petr, Kristensen, Steen Dalby, Hartikainen, Juha, Danchin, Nicolas, Darius, Harald, Fat, Tse Hung, Kiss, Robert Gabor, Pais, Prem, Lev, Eli, De Luca, Leonardo, Goto, Shinya, Ramos Lopez, Gabriel Arturo, Cornel, Jan Hein, Kontny, Frederic, Medina, Felix, Babilonia, Noe, Opolski, Grzegorz, Vinereanu, Dragos, Zateyshchikov, Dmitry, Ruda, Mikhail, Elamin, Omer, Kovar, Frantisek, Dalby, Anthony John, Jeong, Myung Ho, Bueno, Hector, James, Stefan, Chiang, Chern-En, Tresukosol, Damras, Ongen, Zeki, Ray, Kausik, Parkhomenko, Alexander, McGuire, Darren, Kosiborod, Mikhail, Nguyen, Tuan Quang, Wallentin, Lars, Fox, Keith A. A., Eikelboom, John W., Tuomilehto, Jaakko, Lee, Kerry L., Al-Khalidi, Hussein R., Ellis, Stephen J., Hagström, Emil, Holmgren, Pernilla, Heldestad, Ulrika, Hallberg, Theresa, Renlund Grausne, Karin, Alm, Cristina, Michelgård Palmquist, Åsa, Svanberg, Camilla, Capell, Warren H., Nehler, Mark R., Hiatt, William R., Bonaca, Marc P., Houser, Stacey, Bachler, Susie, Jaeger, Nicole, Aunes, Maria, Brusehed, Asa, Chen, Jersey, Dahlof, Bjorn, Dolezalova, Jitka, Domzol, Maciej, Findley, Magdalena, Holmberg, Niclas, Jahreskog, Marianne, Knutsson, Mikael, Kruszewski, Jakub, Leonsson-Zachrisson, Maria, Stark, Maj, Winder, Elin, and Sinnaeve, P

Subjects
Male, Ticagrelor, Cardiac & Cardiovascular Systems, Time Factors, medicine.medical_treatment, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Myocardial Infarction, general clinical cardiology/adult, Coronary Artery Disease, Type 2 diabetes, 030204 cardiovascular system & hematology, Stroke/mortality, antiplatelet therapy, Hypoglycemic Agents/adverse effects, Coronary artery disease, DOUBLE-BLIND, 0302 clinical medicine, Risk Factors, ARTERY-DISEASE, Medicine, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, Myocardial infarction, 1102 Cardiorespiratory Medicine and Haematology, Stroke, Randomized Controlled Trials as Topic, Aspirin, Kardiologi, adult, general clinical cardiology, 60 MG, Ticagrelor/administration & dosage, General Medicine, Middle Aged, Clopidogrel, Treatment Outcome, CLOPIDOGREL, diabetes mellitus, Cardiology, PLATELET INHIBITION, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Trial Designs, 03 medical and health sciences, Diabetes Mellitus, Type 2/diagnosis, Double-Blind Method, Internal medicine, Humans, Hypoglycemic Agents, CARDIOVASCULAR EVENTS, Aspirin/administration & dosage, Myocardial Infarction/mortality, Platelet Aggregation Inhibitors/administration & dosage, Aged, clinical trials, Science & Technology, business.industry, ACUTE CORONARY SYNDROMES, Percutaneous coronary intervention, medicine.disease, ischemic heart disease, ASPIRIN, MYOCARDIAL-INFARCTION, Cardiovascular System & Hematology, Clinical Trials, Phase III as Topic, Diabetes Mellitus, Type 2, Cardiovascular System & Cardiology, Coronary Artery Disease/diagnosis, business, THEMIS Steering Committee, Platelet Aggregation Inhibitors
Abstract

In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients ≥50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of ≥50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention. ispartof: CLINICAL CARDIOLOGY vol:42 issue:5 pages:498-505 ispartof: location:United States status: published

Published
2019

27. Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y12 Receptor Antagonist Effects in Patients With Acute Coronary Syndromes : Insights From the PLATO Trial

Author

Franchi, Francesco, James, Stefan, Ghukasyan, Tatevik, Budaj, Andrzej J., Cornel, Jan H., Katus, Hugo A., Keltai, Matyas, Kontny, Frederic, Lewis, Basil S., Storey, Robert F., Himmelmann, Anders, Wallentin, Lars, Angiolillo, Dominick J., Parkhomenko, Alexander Nikolaevich, Oto, Ali, Skene, Allan, Budaj, Andrzej, Freij, Anneli, Santoso, Anwar, Armando, A, Meier, Bernhard, Yu, Cheuk Man, Cannon, Christopher P., Zambahari, Dato Seri Robaayah, Wu, Delon Wu, Ardissino, Diego, Raev, Dimitar, Kremastinos, Dimitrios, Weaver, Douglas, Paolasso, Ernesto, Giannitsis, Evangelos, Verheugt, Freek, Maurer, Gerald, Katus, Hugo, Emanuelsson, Hakan, Horrow, Jay, Bassand, Jean-Pierre, Spinar, Jindrich, Morais, Joao, Lopez Sendon, Jose, Nicolau, Jose, Seung, Ki-Bae, Teik, Lim Soo, Heras, Magda, Claeys, Marc J., Sabatine, Marc, Vintila, Marius, Ruda, Mikhail, Thorsen, Mona, Kleiman, Neil, Babilonia, Noe, Commerford, Patrick, Gurbel, Paul, Aylward, Phil, Steg, Philippe Gabriel, Theroux, Pierre, Sritara, Piyamitr, Pais, Prem, Becker, Richard, Lassila, Riitta, Harrington, Robert A., Gao, Runlin, Husted, Steen, Duris, Tibor, Chapichadze, Zaza, Franchi, Francesco, James, Stefan, Ghukasyan, Tatevik, Budaj, Andrzej J., Cornel, Jan H., Katus, Hugo A., Keltai, Matyas, Kontny, Frederic, Lewis, Basil S., Storey, Robert F., Himmelmann, Anders, Wallentin, Lars, Angiolillo, Dominick J., Parkhomenko, Alexander Nikolaevich, Oto, Ali, Skene, Allan, Budaj, Andrzej, Freij, Anneli, Santoso, Anwar, Armando, A, Meier, Bernhard, Yu, Cheuk Man, Cannon, Christopher P., Zambahari, Dato Seri Robaayah, Wu, Delon Wu, Ardissino, Diego, Raev, Dimitar, Kremastinos, Dimitrios, Weaver, Douglas, Paolasso, Ernesto, Giannitsis, Evangelos, Verheugt, Freek, Maurer, Gerald, Katus, Hugo, Emanuelsson, Hakan, Horrow, Jay, Bassand, Jean-Pierre, Spinar, Jindrich, Morais, Joao, Lopez Sendon, Jose, Nicolau, Jose, Seung, Ki-Bae, Teik, Lim Soo, Heras, Magda, Claeys, Marc J., Sabatine, Marc, Vintila, Marius, Ruda, Mikhail, Thorsen, Mona, Kleiman, Neil, Babilonia, Noe, Commerford, Patrick, Gurbel, Paul, Aylward, Phil, Steg, Philippe Gabriel, Theroux, Pierre, Sritara, Piyamitr, Pais, Prem, Becker, Richard, Lassila, Riitta, Harrington, Robert A., Gao, Runlin, Husted, Steen, Duris, Tibor, and Chapichadze, Zaza

Abstract

Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P<0.001). Patients with DM+/CKD- and DM-/CKD+ had an intermediate risk profile. The same trend was shown for the individual components of the primary end point and for major bleeding. Compared with clopidogrel, ticagrelor reduced the incidence of the primary end point consistently across subgroups (P-interaction=0.264), but with an increased absolute risk reduction in DM+/CKD+. The effects on major bleeding were also consistent across subgroups (P-interaction=0.288). Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.

Published
2019
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28. Admission Levels of DKK1 (Dickkopf-1) Are Associated With Future Cardiovascular Death in Patients With Acute Coronary Syndromes

Author

Ueland, Thor, Åkerblom, Axel, Ghukasyan, Tatevik, Michelsen, Annika E, Becker, Richard C, Bertilsson, Maria, Himmelmann, Anders, James, Stefan, Siegbahn, Agneta, Storey, Robert F, Kontny, Frederic, Aukrust, Pål, Wallentin, Lars, Ueland, Thor, Åkerblom, Axel, Ghukasyan, Tatevik, Michelsen, Annika E, Becker, Richard C, Bertilsson, Maria, Himmelmann, Anders, James, Stefan, Siegbahn, Agneta, Storey, Robert F, Kontny, Frederic, Aukrust, Pål, and Wallentin, Lars

Abstract

Objective- The Wnt/wingless signaling antagonist DKK1 (dickkopf-1) regulates platelet-mediated inflammation and may contribute to plaque destabilization. We hypothesized that DKK1 would be associated with cardiovascular outcomes. Approach and Results- We determined DKK1 levels in serum samples obtained before randomization, at discharge, and 1 and 6 months in a subset of 5165 patients with acute coronary syndromes in the PLATO trial (Platelet Inhibition and Patient Outcomes; NCT00391872). The median (interquartile range) DKK1 concentrations were 0.61 (0.20-1.27) ng/mL at baseline and increased during follow-up. The hazard ratio (95% CIs) for the composite end point (cardiovascular death, nonprocedural spontaneous myocardial infarction, or stroke) during 1 year of follow-up, per 50% increase in baseline DKK1 concentration, was 1.06 (1.02-1.10), P=0.0011, and remained significant in fully adjusted analysis with 14 conventional clinical and demographic and 6 biochemical variables, including NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-TnT (high-sensitivity troponin T), and GDF-15 (growth differentiation factor 15; 1.05 [1.00-1.09]; P=0.028). This association was mainly driven by the association with cardiovascular death, where a gradual increase in event rates was observed with increasing quartiles of DKK1 (2.7%, 3.0%, 4.3%, and 5.0%) and remained significant and unmodified in fully adjusted analysis (hazard ratio, 1.10 [1.04-1.17]; P=0.002). Change in DKK1 and levels at 1 month were unrelated to outcomes. A modifying effect of ticagrelor on DKK1 discharge levels was observed but not associated with prognosis. Conclusions- In patients with acute coronary syndromes treated with dual antiplatelet treatment, admission DKK1 levels were independently associated with a composite of cardiovascular death, myocardial infarction, or stroke and with cardiovascular death alone.

Published
2019
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30. Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54

Author

Dellborg, Mikael, primary, Bonaca, Marc P, additional, Storey, Robert F, additional, Steg, P Gabriel, additional, Im, Kyung A, additional, Cohen, Marc, additional, Bhatt, Deepak L, additional, Oude Ophuis, Ton, additional, Budaj, Andrezej, additional, Hamm, Christian, additional, Spinar, Jindrich, additional, Kiss, Robert G, additional, Lopez-Sendon, José, additional, Kamensky, Gabriel, additional, Van de Werf, Frans, additional, Ardissino, Diego, additional, Kontny, Frederic, additional, Montalescot, Gilles, additional, Johanson, Per, additional, Bengtsson, Olof, additional, Himmelmann, Anders, additional, Braunwald, Eugene, additional, and Sabatine, Marc S, additional

Published
2019
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33. Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes : Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial

Author

Ueland, Thor, Åkerblom, Axel, Ghukasyan, Tatevik, Michelsen, Annika E., Aukrust, Pål, Becker, Richard C., Bertilsson, Maria, Himmelmann, Anders, James, Stefan K, Siegbahn, Agneta, Storey, Robert F., Kontny, Frederic, Wallentin, Lars, Ueland, Thor, Åkerblom, Axel, Ghukasyan, Tatevik, Michelsen, Annika E., Aukrust, Pål, Becker, Richard C., Bertilsson, Maria, Himmelmann, Anders, James, Stefan K, Siegbahn, Agneta, Storey, Robert F., Kontny, Frederic, and Wallentin, Lars

Abstract

Background-Elevated levels of osteoprotegerin, a secreted tumor necrosis factor-related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Methods and Results-The associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non-coronary artery bypass grafting major bleeding during 1year of follow-up were assessed by Cox proportional hazards models. Event rates of the composite end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and 11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI], 1.21-1.42) for the composite end point but was not significant in adjusted analysis (ie, clinical characteristics and levels of C-reactive protein, troponin T, NT-proBNP [N-terminal pro-B-type natriuretic peptide], and growth differentiation factor-15). The corresponding rates of non-coronary artery bypass grafting major bleeding were 2.4%, 2.2%, 3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36-1.69), and a fully adjusted HR of 1.26 (95% CI, 1.09-1.46). The multivariable association between the osteoprotegerin concentrations and the primary end point after 1month resulted in an HR of 1.09 (95% CI, 0.89-1.33); for major bleeding after 1month, the HR was 1.33 (95% CI, 0.91-1.96). Conclusions-In patients with acute coronary syndrome treated with dual antiplatelet therapy, osteoprotegerin was an independent marker of major bleeding but not of ischemic cardiovascular events. Thus, high osteoprotegerin levels may be useful in increasing awareness of increased bleeding risk in patients with acute co

Published
2018
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35. Long-term ticagrelor for secondary prevention in patients with prior myocardial infarction and no history of coronary stenting: insights from PEGASUS-TIMI 54.

Author

Furtado, Remo H M, Nicolau, Jose C, Magnani, Giulia, Im, Kyungah, Bhatt, Deepak L, Storey, Robert F, Steg, P Gabriel, Spinar, Jindrich, Budaj, Andrzej, Kontny, Frederic, Corbalan, Ramon, Kiss, Robert G, Abola, Maria Teresa, Johanson, Per, Jensen, Eva C, Braunwald, Eugene, Sabatine, Marc S, and Bonaca, Marc P

Abstract

Aims PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup. Methods and results This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1–3 years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15–1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68–0.99) and with prior stenting (HR 0.85, 95% CI 0.75–0.96; P for interaction = 0.76). Conclusion Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting. ClinicalTrials.gov Identifier NCT01225562. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Published
2020
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36. Biomarkers and Coronary Lesions Predict Outcomes after Revascularization in Non-ST-Elevation Acute Coronary Syndrome

Author

Lindholm, Daniel P, James, Stefan K, Bertilsson, Maria, Becker, Richard C, Cannon, Christopher P, Giannitsis, Evangelos, Harrington, Robert A, Himmelmann, Anders, Kontny, Frederic, Siegbahn, Agneta, Steg, Philippe Gabriel, Storey, Robert F, Velders, Matthijs A, Weaver, W Douglas, Wallentin, Lars, Lindholm, Daniel P, James, Stefan K, Bertilsson, Maria, Becker, Richard C, Cannon, Christopher P, Giannitsis, Evangelos, Harrington, Robert A, Himmelmann, Anders, Kontny, Frederic, Siegbahn, Agneta, Steg, Philippe Gabriel, Storey, Robert F, Velders, Matthijs A, Weaver, W Douglas, and Wallentin, Lars

Abstract

BACKGROUND: Risk stratification in non-ST-elevation acute coronary syndrome (NSTE-ACS) is currently mainly based on clinical characteristics. With routine invasive management, angiography findings and biomarkers are available and may improve prognostication. We aimed to assess if adding biomarkers [high-sensitivity cardiac troponin T (cTnT-hs), N-terminal probrain-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15)] and extent of coronary artery disease (CAD) might improve prognostication in revascularized patients with NSTE-ACS. METHODS: In the PLATO (Platelet Inhibition and Patient Outcomes) trial, 5174 NSTE-ACS patients underwent initial angiography and revascularization and had cTnT-hs, NT-proBNP, and GDF-15 measured. Cox models were developed adding extent of CAD and biomarker levels to established clinical risk variables for the composite of cardiovascular death (CVD)/spontaneous myocardial infarction (MI), and CVD alone. Models were compared using c-statistic and net reclassification improvement (NRI). RESULTS: For the composite end point and CVD, prognostication improved when adding extent of CAD, NT-proBNP, and GDF-15 to clinical variables (c-statistic 0.685 and 0.805, respectively, for full model vs 0.649 and 0.760 for clinical model). cTnT-hs did not contribute to prognostication. In the full model (clinical variables, extent of CAD, all biomarkers), hazard ratios (95% CI) per standard deviation increase were for cTnT-hs 0.93(0.81-1.05), NT-proBNP 1.32(1.13-1.53), GDF-15 1.20(1.07-1.36) for the composite end point, driven by prediction of CVD by NT-proBNP and GDF-15. For spontaneous MI, there was an association with NT-proBNP or GDF-15, but not with cTnT-hs. CONCLUSIONS: In revascularized patients with NSTE-ACS, the extent of CAD and concentrations of NT-proBNP and GDF-15 independently improve prognostication of CVD/spontaneous MI and CVD alone. This information may be useful for selection of patients who might benefit from mor, Författarna företräder The PLATO Investigators.

Published
2017
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37. Biomarkers and Coronary Lesions Predict Outcomes after Revascularization in Non–ST-Elevation Acute Coronary Syndrome

Author

Lindholm, Daniel, primary, James, Stefan K, primary, Bertilsson, Maria, primary, Becker, Richard C, primary, Cannon, Christopher P, primary, Giannitsis, Evangelos, primary, Harrington, Robert A, primary, Himmelmann, Anders, primary, Kontny, Frederic, primary, Siegbahn, Agneta, primary, Steg, Philippe Gabriel, primary, Storey, Robert F, primary, Velders, Matthijs A, primary, Weaver, W Douglas, primary, and Wallentin, Lars, primary

Published
2017
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38. Abstract 12851: Osteoprotegerin is Associated With Major Bleeding but Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes - Insights From the PLATelet Inhibition and Patient Outcomes (PLATO) Trial

Author

Ueland, Thor, primary, Åkerblom, Axel, additional, Ghukasyan, Tatevik, additional, Michelsen, Annika E, additional, Aukrust, Pål, additional, Becker, Richard C, additional, Bertilsson, Maria, additional, Himmelmann, Anders, additional, James, Stefan K, additional, Siegbahn, Agneta, additional, Storey, Robert F, additional, Kontny, Frederic, additional, and Wallentin, Lars, additional

Published
2016
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39. Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y12 Receptor Antagonist Effects in Patients With Acute Coronary Syndromes: Insights From the PLATO Trial.

Author

Franchi, Francesco, James, Stefan K., Lakic, Tatevik Ghukasyan, Budaj, Andrzej J., Cornel, Jan H., Katus, Hugo A., Keltai, Matyas, Kontny, Frederic, Lewis, Basil S., Storey, Robert F., Himmelmann, Anders, Wallentin, Lars, Angiolillo, Dominick J., Ghukasyan Lakic, Tatevik, and PLATO Investigators

Published
2019
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40. Long-term Tolerability of Ticagrelor for the Secondary Prevention of Major Adverse Cardiovascular Events

Author

Bonaca, Marc P., primary, Bhatt, Deepak L., additional, Oude Ophuis, Ton, additional, Steg, P. Gabriel, additional, Storey, Robert, additional, Cohen, Marc, additional, Kuder, Julia, additional, Im, Kyungah, additional, Magnani, Giulia, additional, Budaj, Andrzej, additional, Theroux, Pierre, additional, Hamm, Christian, additional, Špinar, Jindrich, additional, Kiss, Robert G., additional, Dalby, Anthony J., additional, Medina, Felix A., additional, Kontny, Frederic, additional, Aylward, Philip E., additional, Jensen, Eva C., additional, Held, Peter, additional, Braunwald, Eugene, additional, and Sabatine, Marc S., additional

Published
2016
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41. Activated Leukocyte Cell Adhesion Molecule (ALCAM) And Outcomes In Acute Coronary Syndromes : A Plato Biomarker Substudy

Author

Wallentin, Lars, Michelsen, Annika E., Aukrust, Pal, Becker, Richard, Bertilsson, Maria, Budaj, Andrzej, Cornel, Jan, Himmelmann, Anders, Husted, Steen, Siegbahn, Agneta, Storey, Robert, Kontny, Frederic, Ueland, Thor, Wallentin, Lars, Michelsen, Annika E., Aukrust, Pal, Becker, Richard, Bertilsson, Maria, Budaj, Andrzej, Cornel, Jan, Himmelmann, Anders, Husted, Steen, Siegbahn, Agneta, Storey, Robert, Kontny, Frederic, and Ueland, Thor

Published
2015
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42. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

Author

Bhatt, Deepak L, Steg, Philippe Gabriel, Mehta, Shamir R, Leiter, Lawrence A, Simon, Tabassome, Fox, Kim, Held, Claes, Andersson, Marielle, Himmelmann, Anders, Ridderstråle, Wilhelm, Chen, Jersey, Song, Yang, Diaz, Rafael, Goto, Shinya, James, Stefan K, Ray, Kausik K, Parkhomenko, Alexander N, Kosiborod, Mikhail N, McGuire, Darren K, Harrington, Robert A, Santos, Vladimir, Jain, Ashit, Lendel, Irina, Russo, Michael, Haught, W H, Bouza, Manuel, Gogia, Harinder, Banerjee, Supratim, Kichura, George, Kantaros, Louis, Padron, Francisco, Passi, Rakesh, Stone, Jay, Pursley, Michael, D'Urso, Michael, Gardner, Timothy, Bennett, James, Nour, Khaled, Saini, Satinder, Zhang, Wenwu, Kumbhani, Dharam, Thomas, Dustin, Angiolillo, Dominick, Bertolet, Barry, Roman-Miranda, Amaury, Black, Robert, Manshadi, Ramin, Vaca, Carlos, Blanco, Antonio, Napoli, Mark, Brabham, David, Akyea-Djamson, Ayim, Desai, Pratik, Prasada, Sudhir, Khaira, Ajit, Forgosh, Leslie, Lieber, Ira, Umpierrez, Guillermo, Singal, Dinesh, Londono, Juan, Fraser, Neil, Ruiz, Jose, Vega, Damaris, Rodriguez, Lilia, Brown, Christopher, Syed, Faizullah, Aggarwala, Guarav, Eaves, William, Foster, Michael, Gupta, Dinesh, Avino, David, Asfour, Wail, Tonnessen, Glen, Zhao, Xue-Qiao, Singh, Narendra, Brockmyre, Andrew, Lepor, Norman, Shammas, Nicolas, Blick, David, Hearne, Steven, Prodafikas, John, Carell, Edgar, Izzo, Mark, Karim, Amin, Zakhary, Bosh, Atieh, Mahmoud, Leichter, Steven, Meadows, Charles, Hotchkiss, David, Abu-Fadel, Mazen, Wiseman, Alan, Bander, Jeffrey, Shah, Mahesh, Banerjee, Subhash, Ganim, Ricky, Sopko, Karen, Khan, Misal, Lloret, Ramon, Weirick, Troy, Mehta, Rajendra, Thadani, Udho, Bhargava, Anuj, Kosiborod, Mikhail, Moya, Jaynier, Staniloae, Cezar, Guerra, Yamirka D, Chhabra, Anil, Kosmicki, Douglas, Shaheen, Wassim, Mohammed, Akber, Bitters, J'Cinda, Pattanayak, Jan, Javier, Julian, Srivastava, Sunny, Phillips, Roland, Al-Amin, Jessie, Lillestol, Michael, Simpson, Patrick, Hazan, Lydie, Amin, Amit, Shah, Gopi, Korpas, Denes, Platt, Bruce, Dickert, Jim, Puente, Orlando, Hiotis, Louis, Doyle, Timothy, Rajan, Raj, Meholick, Alan, Gring, Christian, Hage-Korban, Elie, Feldman, Robert, Colfer, Harry, Butman, Samuel, Foster, Malcolm, Hart, Terence, Huling, Randall, Eshaghian, Shervin, Quintana, Ofsman, Cheung, Deanna, Handel, Franklin, Rodriguez, Mara, Suh, David, Gordon, Paul, Pressman, Gregg, Bauer, Michael, French, William, Barettella, Mark, Chatrathi, Sridhar, Suresh, Damodhar, Goldberg, Ronald, Huth, Mark, Younis, Liwa, Rahman, Aref, Mascolo, Richard, Welch, Michelle, Suneja, Randeep, Smith, Stephen, Shurmur, Scott, Agaiby, John, Jingo, Ahmad, Johnston, Janice, Beth, Mary, Vlastaris, Anthony, Kemp, Susan, Taheri, Hamid, Pereira, Edward, Deyoung, Michael, Hawa, Zafir, Smith, Ray, Galski, Thomas, Garas, Samer, Reddy, M, Sharma, Susheel, Hargrove, Joeseph, Treasure, Charles, Emerson, Ronald, Haddad, Tariq, Rohr, Kathryn, Levinson, Larry, Gaona, Raul, Uretsky, Barry, Maheshwari, Hiralal, Lee, Denny, Kinnaman, Stephanie, Singal, Robert, Geohas, Jeffrey, Gigliotti, Osvaldo, Raisinghani, Ajit, Khurana, Charanjit, Hella, Brent, Kelberman, Michael, Voyce, Steven, Singh, Sanjay, Lo, Eric, Singh, Pradeep, Goodfellow, Ross, Fischer, Stuart, Lorraine, Richard, Turner, Traci, Shanes, Jeffrey, Busch, Robert, Broker, Robert, Zaniewski, Michelle, Pounds, Kevin, Debs-Perez, Giselle, Ong, Stephen, Frandsen, Brad, Fullington, Douglas, Jaffrani, Naseem, Khan, Ahtaram, Lee, Marcus, Pouzar, Joe, Revtyak, George, Gonzalez, Julian, Nakhle, Samer, Murillo, Abel, Young, Douglas, Makam, Sashi, Syed, Mushtaq, Woolf, Kevin, Grena, Paul, Alfata, Sarab, Mahal, Sharan, Hoffman, David, Kizhakekuttu, Tinoy, Deering, Joseph, Bhavsar, Janak, Mikesell, Scott, Wilson, William, Wilson, Vance, El, Salah, Spinale, Francis, Kannarkat, Vinod, Rao, Sunder, Hanson, Lenita, Bertsch, John, Gonzalez-Ortiz, Elena, Severino, Norma, Willis, John, Schock, Joel, Bakhtari, Ladan, Gazmuri, Raul, Ansari, Saadat, Hall, Jason, Mehta, Arvind, Shealy, Neal, Zarich, Stuart, Singh, Deovrat, Vora, Kishor, Andrawis, Nabil, Molter, Darron, Maron, David, Cardona, Jose, D'Agostino, Ronald, Arshad, Tamjeed, Samaan, Rodney, Jones, David, Presser, Dale, Heath, John, Green, Sandy, Bittar, George, Henry, Sheldon, Korn, David, Schmedtje, John, Nadar, Venkatesh, Graham, Bruce, Labroo, Ajay, Clavijo, Leonardo, Roseman, Hal, Ledesma, Gilbert, Rosen, Robert, Dor, Isaac, Kirby, William, Sutton, Jennefer, Eder, Frank, Iteld, Bruce, Gomez-Cortes, Jose, Buchbinder, Maurice, Kasper, Joseph, Terrelonge, Antonio, Torres, Gustavo, Jagielo, Ted, Alvarez, Jose, Handelsman, Yehuda, Guillen, Mario, Richwine, Randall, Lewy-Alterbaum, Lorena, Corder, Clinton, Arvind, Moogali, Bolshoun, David, Mikhail, Magdy, Minton, Stephen, Alvarado, Odilon, Abbott, J, Cauthen, Brett, Welter, Ryan, Mintz, Randy, Cox, John, Quick, Annette, Weiss, Melvin, Dy, Johnny, Zebrack, James, Gandelman, Glenn, Hegde, Vinayak, Silver, Marc, DeGregorio, Michele, Lawson, William, Paa, Christopher, Bortnick, Anna, Krolick, Merrill, Sotolongo, Rodolfo, Cheirif, Jorge, Kumar, Priya, Nadar, Venkatesh, Jetty, Preetham, Patel, Ambar, Kruk, Mariusz, Kobielusz-Gembala, Iwona, Rewerska, Barbara, Madrzejewski, Adam, Milewski, Krzysztof, Cygler, Jerzy, Petryka-Mazurkiewicz, Joanna, Jastrzebski, Waldemar, Korecki, Janusz, Fil, Wojciech, Prokopczuk, Janusz, Bochenek, Anna, Wujkowski, Marek, Witek, Robert, Konczakowski, Piotr, Miekus, Pawel, Szczasny, Marcin, Musial, Wlodzimierz, Cymerman, Krzysztof, Lampart, Jacek, Mikosinski, Jacek, Szynal, Slawomir, Fares, Issa, Opolski, Grzegorz, Mazur, Stanislaw, Wozakowska-Kaplon, Beata, Bijata-Bronisz, Renata, Wierucki, Lukasz, Losa, Beata, Drelich, Grzegorz, Konieczny, Marek, Starczewski, Pawel, Pawlowicz, Lidia, Jesionowski, Pawel, Jurowiecki, Jaroslaw, Gniot, Jacek, Czyzycki, Mariusz, Stania, Karol, Kucharczyk-Bauman, Izabela, Busz-Papiez, Benita, Karczmarczyk, Agnieszka, Sudnik, Wanda, Koszek, Alina, Kolodziej, Piotr, Skwarna, Bartosz, Jaramillo, Nicolás, Jankowski, Maciej, Czochra, Wojciech, Kinasz, Leszek, Miklaszewicz, Beata, Stasinska, Teresa, Pluta, Wladyslaw, Basiak, Marcin, Rusicka, Teresa, Niedbal-Yahfouf, Izabela, Popenda, Grazyna, Korzeniak, Romuald, Mirek, Agnieszka, Mariankowski, Rafal, Wojnowski, Lukasz, Korol, Marek, Baszak, Jacek, Podolec, Piotr, Piesiewicz, Wojciech, Zurakowski, Aleksander, Luengas, Carlos, Skura, Marek, Pilecki, Piotr, Majchrzak, Piotr, Krzyzagórska, Ewa, Drozd, Marcin, Kaczmarek, Barbara, Sliwinska, Teresa, Zelazowska, Katarzyna, Sztembis, Rafal, Landa, Katarzyna, Matyszczak-Toniak, Lidia, Strojek, Krzysztof, Piepiorka, Marek, Malinowski, Robert, Górska, Maria, Stolarczyk-Sowa, Edyta, Romanowski, Leszek, Zinka, Elzbieta, Reszka, Zygfryd, Skierkowska, Joanna, Uzunow, Anna, Laskowska-Derlaga, Ewa, Puntus, Ekaterina, Kosmacheva, Elena D, Koziolova, Natalia, Pavlov, Prokhor, Supryadkina, Tatiana, Didenko, Yury, Kopylov, Philipp, Kazakov, Andrei, Aksentiev, Sergei, Vishneva, Elena, Repin, Alexey, Smolenskaya, Olga, Mantserova, Olga, Khrustalev, Oleg, Privalova, Elena, Konstantinov, Vladimir, Boldueva, Svetlana, Ezhov, Andrey, Chernyavsky, Alexander, Kamalov, Gadel, Galyavich, Albert, Zubeeva, Galina, Nechaeva, Galina, Shustov, Sergey, Dzhaiani, Nino, Treshkur, Tatiana, Osokina, Nataliya, Panov, Alexey, Shutemova, Elena, Makukhin, Valeriy, Kropotina, Tatiana, Tsyba, Larisa, Karpov, Yuri, Sizova, J M, Ballyuzek, Marina, Tarasov, Nikolay, Demchenko, Elena, Barbarash, Olga, Moiseev, Valentin, Markov, Valentin, Kuznetsov, Vadim, Viktorova, Inna, Sergienko, Igor, Ermoshkina, Lyudmila, Khasanov, Niyaz, Khlevchuk, Tatiana, Baglikov, Andrey, Shalaev, Sergey, Zonova, Elena, Reznik, Elena, Haisheva, Larisa, Morugova, Tatyana, Lomakin, Nikita, Vishnevsky, Alexander, Shvarts, Yuri, Magnitskaya, Olga, Mikhailusova, Marina, Pavlysh, Elena, Libov, Igor, Zateyschikova, Anna, Kostenko, Victor, Edin, Anton, Khovaeva, Yaroslava, Zakharov, Konstantin, Stryuk, Raisa, Khirmanov, Vladimir, Kanorskiy, Sergey, Yakushin, Sergey, Barabashkina, Anna, Li, Hongwei, Zhao, Qiang, Zhang, Jian, Ma, Jianhua, He, Yong, Luo, Ming, Zhang, Aidong, Zhang, Ningru, Chai, Yingru, Ma, Genshan, Wang, Hao, Liu, Zhigang, He, Lanjie, Song, Zhifang, Dong, Xiaolin, Tao, Liang, Li, Zhanquan, Su, Xi, Kong, Xiangqing, Niu, Heping, Ge, Junbo, Luo, Zhurong, Huang, Wenjun, Peng, Daoquan, Yuan, Zuyi, Milanova, Maria, Tenev, Doncho, Gogov, Antoni, Karageorgiev, Dimitar, Kolchev, Todor, Rusev, Nikolay, Georgieva, Nikolina, Kondov, Rumen, Rusinov, Veselin, Petrov, Ivo, Stanchev, Georgi, Konteva, Mariana, Dincheva, Adriana, Yaneva, Zdravka, Vatova, Ralitsa, Ilieva, Katya, Runev, Nikolai, Kolomanov, Borislav, Petrov, Ivan, Iliev, Nikolay, Tisheva, Snezhanka, Chompalova, Boryana, Tokmakova, Maria, Raev, Dimitar, Byanov, Kolyo, Markov, Dimitar, Mihov, Lenko, Mihov, Atanas, Milcheva, Nora, Minchev, Milen, Mollov, Mihail, Borisov, Borislav, Tihchev, Tihomir, Karakolev, Venelin, Dimov, Bojidar, Georgiev, Svetoslav, Smilov, Lachezar, Koo, Bon K, Ahn, Taehoon, Hong, Soon J, Yoon, Junghan, Oh, Seok K, Jeong, Myung H, Kim, Doo-Il, Chang, Kiyuk, Kim, Weon, Hahn, Joo-Yong, Cha, Kwang S, Lee, Jung-Hee, Choi, Si-Wan, Nam, Chang-Wook, Chae, In-Ho, Park, Yong H, Tahk, Seung-Jea, Shin, Won-Yong, Chae, Jei-Keon, Kim, Byung J, Bae, Jang-Whan, Park, Woo J, Rha, Seung W, Choi, Young J, Hwang, Jin-Yong, Park, Hun S, Baracioli, Luciano, Guimaraes, Fabio, Vasconcellos, Eduardo, Saraiva, José, Pereira, Adamastor, Santos, Queulla, Rossi, Paulo, Maia, Lilia, Madeira, Miguel, Pereira, Marcio, Botelho, Roberto, Reis, Gilmar, Eliaschewitz, Freddy, Borges, Joao, Nascimento, Carlos, Fortes, Jose A, de Souza, Weimar, Pimentel, Pedro, Hissa, Miguel, Franchetti, Marcos, Precoma, Dalton, Ortiz, Costantino, Hernandes, Mauro, Saporito, Wladmir, dos Santos, Fabio R, Kormann, Adrian, Neuenschwander, Fernando, Dutra, Oscar, Rassi, Nelson, Tanajura, Luiz, Souza, Juliana, Junior, Delcio S, Leaes, Paulo, Forte, Adriana, Bonansea, Teresa C, Marin, Jose, Machado, Bruno, Cerqueira, Maria J, Silva, Frederico, Michalaros, Yorghos, Manenti, Euler, Cercato, Cintia, Figueiredo, Estevao, Liu, Ming-En, Wang, Yi-Chih, Lee, Tsung-Ming, Fang, Chih, Wu, Yen-Wen, Ueng, Kwo-Chang, Sheu, Huey-Herng, Lai, Wen T, Hsieh, I-Chang, Chen, Zhih-Cherng, Lee, Mu-Jang, Chiang, Chern, Shyu, Kou-Gi, Hsia, Chien-Hsun, Mar, Guang-Yuan, Chan, Shih-Hung, Wu, Chih-Cheng, Tseng, Wei-Kung, Chang, Kuan-Cheng, Yeh, Hung-I, Wang, Ji-Hung, Hou, Charles, Sorokina, Inna, Dolzhenko, Maryna, Horoshko, Olha, Karpenko, Oleksandr, Rudenko, Leonid, Vakaliuk, Igor, Kulyk, Anna, Levchenko, Olena, Prokhorov, Oleksandr, Reshotko, Dmytro, Sorokivskyy, Mykhaylo, Velichko, Nataliia, Maslovskyi, Valentyn, Teliatnikova, Zinaida, Dotsenko, Sergiy, Krakhmalova, Olena, Kraiz, Igor, Zharinova, Viktoria, Bula, Larysa, Kaydashev, Igor, Molodtsov, Valeriy, Rasputina, Lesya, Pidlisna, Viktoriya, Lysunets, Olena, Kravchenko, Anatoliy, Glushko, Liubomyr, Khomazyuk, Tetyana, Svyshchenko, Yevgeniya, Parkhomenko, Oleksandr, Mankovsky, Boris, Abrahamovych, Orest, Yagensky, Andriy, Stanislavchuk, Mykola, Vasilyeva, Larisa, Sokolova, Liubov, Sychov, Oleg, Tseluyko, Vira, Kyrychenko, Igor, Rishko, Mykola, Furkalo, Sergiy, Gallo, Richard, Bertrand, Olivier, Mehta, Shamir, Constance, Christian, Sussex, Bruce, Zadra, Remo, Kouz, Simon, Chehayeb, Raja, Pandey, Amritanshu, Dion, Danielle, Bailey, Gordon, Hill, Laurie, Ramanathan, Krishnan, Dorsch, Micha, Nanji, Alykhan, Babapulle, Mohan, Montigny, Martine, Gosselin, Gilbert, Dehghani, Payam, Rupka, Dennis, Le May, Michel, Pichette, Francis, St-Maurice, Francois, Teefy, Patrick, Mansour, Samer, Kassam, Saleem, Cheung, Stephen, Siega, Anthony D, O'Keefe, Dennis, Sabbah, Eric, Bell, Alan, Chouinard, Guy, Wong, Brian, Miller, Mark, Gaudet, Daniel, Lachance, Pierre, Bata, Iqbal, Petrella, Robert, Gossard, Denis, Dumas, Richard, Ing, Douglas, Boyrazian, Hagop, Bessoudo, Ricardo, Huynh, Thao T, Hart, Randy, Belle-Isle, Jasmin, Shukla, Dinkar, Kelly, Allan, Mazza, Giuseppe, Cha, James, Henein, Sam, Frechette, Andre, Vizel, Saul, Liutkus, Joanne F, O'Mahony, Michael, Halperin, Frank, Kooy, Jacobus, Graham, John, Bailey, Allan, Wojcik, Ronald, Wilderman, Igor, Turi, Tibor, Motyovszki, Ákos, Merkely, Béla, Király, Csaba, Andrássy, Péter, Sárszegi, Zsolt, Fülöp, Tibor, Zilahi, Zsolt, Édes, István, Papp, Andras, Müller, Gábor, Czigány, Anna, Zólyomi, Szilárd, Korányi, László, Takács, János, Juhász, Ferenc, Benczur, Bela, Kancz, Sándor, Földi, András, Nagy, András C, Bakai, Judit, Greschik, István, Püski, László, Nagy, László, Kirschner, Róbert, Kuchar, Roman, Hajek, Petr, Busak, Ladislav, Michalik, Daniel, Matyasek, Ivo, Marusincova, Ivana, Kucera, Dusan, Jerabek, Ondrej, Honkova, Michaela, Dedek, Vratislav, Rihacek, Ivan, Kos, Pavel, Slaby, Josef, Machkova, Martina, Zidkova, Eva, Elbl, Lubomir, Grunfeldova, Hana, Carda, Jiri, Mrozek, Vladimir, Maly, Jiri, Milkovic, Richard, Malecha, Jan, Skalicka, Hana, Oral, Ivo, Krcova, Eva, Lisa, Libor, Belohlavek, Jan, Miklik, Roman, Cermak, Ondrej, Bednarova, Jana, Peroutka, Zdenek, Spinar, Jindrich, Wilke, Andreas, Appel, Karl-Friedrich, Taggeselle, Jens, Förster, Andreas, Toursarkissian, Nicole, Schmidt, Ekkehard, Bott, Jochen, Al-Zoebi, Ayham, Hennig, Dirk, Fischer, Sabine, Schön, Norbert, Sauter, Joachim, Simonis, Gregor, Nischik, Ruth, Rieker, Werner, Schenkenberger, Isabelle, Behnke, Thomas, Klausmann, Gerhard, Jeserich, Michael, Trenk, Dietmar, Weigmann, Ingo, Reuter, Hannes, Rummel, Reinhard, von Münchhausen, Candy, von Engelhardt, Charlotte, Horibe, Eishun, Shibasaki, Taro, Sato, Tomohiko, Kakuta, Tsunekazu, Michishita, Ichiro, Tan, Michinao, Ishiki, Ryoji, Aoyama, Takahiko, Higashiue, Shinichi, Niijima, Yawara, Idogaki, Akira, Hasegawa, Toru, Kiyosue, Arihiro, Tomobuchi, Yoshiaki, Kawamitsu, Katsunori, Kawasaki, Satsuki, Hata, Yoshiki, Fukui, Kazuki, Seki, Kozaburo, Takenaka, Takashi, Abe, Mitsuru, Utsu, Noriaki, Oono, Atsuyuki, Mitsuo, Kazuhisa, Sueyoshi, Atsushi, Hirohata, Atsushi, Tsujimoto, Mitsuru, Ueda, Osamu, Takase, Shinichi, Suzuki, Masahiro, Sakuragi, Satoru, Yamamoto, Fumi, Fujimoto, Noritaka, Kakinoki, Shigeo, Sugiura, Tatsushi, Sugino, Hiroshi, Nakamura, Toshihiro, Goto, Shinya, Kadokami, Toshiaki, Uehara, Hiroki, Ono, Masahiro, Yokoya, Koichi, Koike, Akihiro, Komatsu, Sei, Sonoda, Masahiro, Ueno, Hideki, Doi, Tomofumi, Takagi, Yuichiro, Fujimoto, Kazuteru, Eki, Yutaka, Okubo, Munenori, Sasaki, Kenichiro, van Eck, Martijn, Ronner, Eelko, The, Salem, van de Wal, Ruud, Nierop, Pieter, de Nooijer, Cornelis, The, Salem, The, Salem, Werner, Henri, Westendorp, Iris, van der Zwaan, Coen, Crijns, Hendrikus, Cornel, Jan H, Strikwerda, Sipke, Bos, Robert, de Melker, Edwin, Kuijper, Adrianus, Louwerenburg, Hans, Plomp, Jacobus, Dantzig, Jan-Melle, Prins, Francisco, van Kesteren, Henricus, Willems, Frank, Amoroso, Giovanni, Carnero, Gabriela, Duronto, Ernesto, Besada, Diego, Chacon, Carolina, Zangroniz, Pedro, Solis, Silvana, Liberman, Alberto, Sernia, Virginia, Alvarisqueta, Andres, Maffei, Laura, Vilamajo, Oscar G, García, Celso, Sicer, Maximiliano, Muntaner, Juan, Bordonava, Anselmo, Albisu, Juan, Zanini, Alejandra, Rista, Lucas, Hominal, Miguel, Estrada, José N, Prado, Aldo, Gosparini, Diego M, Schiavi, Beatriz, Castillo, Armando G, Ruíz, José G, Martinez, Guillermo R, López, Víctor G, Rosas, Enrique L, Lopez, Gabriel R, Cantu, Elias G, de los Ríos Ibarra, Manuel, Padilla, Francisco P, Carrasco, Jose P, Carrillo, Luis V, García, Joel D, Askar, Alfredo N, Salinas, Carlos A, Gamba, Marco A, Sanchez, Carlos G, Cantú, Arnulfo G, Sánchez, Raul V, Madrigal, Jaime C, Urbano, Rafael H, Romo, Andrés Í, González Juanatey, José R, Racugno, Paolo, Fillat, Angel C, de la Torre Hernández, José M, Peláez, Juan A, Cortada, Jorge B, Pavia, Pablo G, Navarro, Manuel J, Asenjo, Roberto M, Díaz, Francisco F, Peligero, Eduard B, Manterola, Fernando A, Ortiz, Antonio F, Mediavilla García, Juan D, Ortuño, Francisco M, Vera, Tomás R, González, Alfonso S, Viñas, Jaime A, Fernández Portales, Francisco J, Mayordomo, Petra S, Ojeda, Francisco B, Domínguez, Antonio R, González, Rosa S, Guerrero, Diego B, Ruiz Nodar, Juan M, Marimon, Xavier G, Margáez, José G, Aguilera, Roberto M, Díaz Fernández, José F, Zamorano Gómez, José L, González, Vicente B, del Blanco, Bruno G, Pérez, Ignacio P, Moreno, Mercé R, Ereño, Ainhoa R, García Lledó, José A, Prieto, Juan, Villablanca, Alex, Raffo, Carlos, Pincetti, Christian, Conejeros, Carlos, Roman, Oscar, Rodriguez, Manuel, Varleta, Paola, Goldberg, Cindy, Sandoval, Jorge, Arriagada, German, Leon, Lucio, Potthoff, Sergio, Cobos, Jorge, Figueroa, Christian, Makotoko, Ellen, Fourie, Nyda, Burgess, Lesley, Nortje, Hendrik, Theron, Rust, Pillai, Perumal, Ranjith, Naresh, Trokis, Julien, Pillay, Soobramoney, Reddy, Jeevren, Nunkoo, Theema, Kapp, Cornelia, Urbach, Dorothea, Distiller, Lawrence, Horak, Adrian, van Zyl, Louis, Coetzee, Kathleen, Punt, Zelda, Bayat, Junaid, Dawood, Saleem, Mitha, Ismail, Padayachee, Trevenesan, Hoosen, Farzana, Dalby, Anthony, Prabhavathi, Gowdaiah, Prakash, Mehta, Vimal, Chag, Milan, Gadkari, Milind, Ramamurthee, Kannaiyan, Das, Asit, Sawhney, Jitendra S, Banerjee, Suvro, Sathe, Prachee, Adhyapak, Srilakshmi, Nguyen, Tuan, Pham, Vinh, Do, Huan, Nguyen, Anh, Nguyen, Hien, Truong, Binh, Jamil-Copley, Shahnaz, Lang, Chim, Pell, Alastair, Zaman, Azfar, Storey, Robert, Swanson, Neil, Smith, Simon, Sharman, David, Braganza, Denise, Hammond, Peter, Moriarty, Andrew, Bain, Stephen, Pye, Maurice, Sharp, Andrew, Blagden, Mark, Randeva, Harpal, Myhill, Timothy, Viswanathan, Girish, Keeling, Philip, Clifford, Piers, Saxena, Manish, Lyons, Kristopher, McMurray, John, Jaafar, Feeroz, Murphy, Clare, Cartwright, Simon, Abouglila, Kamal, Antalik, Lubomir, Krajci, Peter, Urban, Miroslav, Fazekas, Frantisek, Pella, Daniel, Koleny, Daniel, Vykoukalova, Tatiana, Macek, Vladimir, Vinanska, Daniela, Jamriskova, Livia, Such, Slavomir, Fulop, Peter, Farsky, Stefan, Bugan, Viliam, Strbova, Jaroslava, Micko, Karol, Palka Jr, Juraj, Sivak, Vladimir, Kristensen, Dalby, Refsgaard, Jens, Holmvang, Lene, Dixen, Ulrik, Nielsen, Henrik, Egstrup, Kenneth, Jensen, Lisette O, Sykulski, Roman, Rasmussen, Ole, Andries, Alin, Luckow, Anders, Nielsen, Gitte, Sørensen, Torben, Wongvipaporn, Chaiyasith, Chamnarnphol, Noppadol, Srimahachota, Suphot, Sansanayudh, Nakarin, Kuanprasert, Srun, Tresukosol, Damras, Sookananchai, Bancha, Kanadasi, Mehmet, Ozcan, Turkay, Kucuk, Murathan, Ongen, Zeki, Okuyan, Ertugrul, Arat, Alev, Acikel, Sadik, Yalcin, Ahmet, Guray, Umit, Ceyhan, Ceyhun, Ozer, Necla, Arslan, Sakir, Angerås, Oskar, Johnston, Nina, Weiderman, Ann-Charlotte, Bandh, Stellan, Hansen, Ole, Larnefeldt, Hans, Kusiak, Dawid, Lindholm, Carl-Johan, Hedman, Anders, Erlinge, David, Curiac, Dan, Lundman, Pia, Zucconi-Mazzini, Roberto, Aladellie, Layth, Jensen, Jens, Verwerft, Jan, Vrolix, Mathias, Faes, Dirk, Striekwold, Harry, Sinnaeve, Peter, Timmermans, Patrick, Guedes, Antoine, Delforge, Marc, Nimmegeers, Jan, Stammen, Francis, Buysschaert, Ian, Hoffer, Etienne, Hollanders, Geert, Vervoort, Geert, Coussement, Patrick, de Maeseneire, Stefan, Janssens, Luc, Gravdal, Stein A, Risberg, Knut, Gullestad, Lars, Hofseth, Ola D, Nilsen, Dennis, Lappegård, Knut T, van den Heuvel, Christian, Gibbs, Charlotte, Khusrawi, Alamdar, Arora, Satish, Tomala, Tadeusz, Kjærnli, Thorbjørn, Berg-Johansen, Jan, Hagemeier, Robert, Skjelvan, Gunnar, Colquhoun, David, Amerena, John, Morbey, Claire, Hammett, Christopher, Dart, Anthony, Lehman, Ronald, Hamilton, Andrew, Worthley, Matthew, Purnell, Peter, Whelan, Alan, MacIsaac, Richard, Arya, Ktut, Linjawi, Sultan, Proietto, Joseph, Prasad, Lakshman, Rodriguez, Aldo, Godoy, Armando, Rodriguez, Victor, Berrospi, Percy, Chavez, Carlos, Negron, Sandra, Heredia, Javier, Medina, Felix, Manrique, Helard, Cabrera, Walter, Cordova, Fernando, Quinteros, Trinidad, Haro, Jaime M, Regalado, Susana, Guitton, Javier, Arbanil, Hugo, Pansieri, Michel, Decoulx, Eric, Goube, Pascal, de Labriolle, Axel, Labeque, Jean N, Range, Gregoire, Cottin, Yves, Montalescot, Gilles, Cayla, Guillaume, Danchin, Nicolas, Angoulvant, Denis, Ferrario, Emile, Elbaz, Meyer, Dubreuil, Olivier, Steg, Philippe G, Fontaine, Caroline, Sorbets, Emmanuel, Omer, Hafiz, Al-Saif, Shukri, Al-Faleh, Hussam, Al-Shehri, Abdullah, Alshehri, Halia, Bazari, Rasha, Hei, Pak, Ying, Man, Chan, Michael, Wong, Michelle, Ma, Ronald, Siu, Shing C, Tsang, Chiu C, Ferrario, Maurizio, Assanelli, Emilio, Senni, Michele, Piatti, Piermarco, Calabrò, Paolo, Urbinati, Stefano, Michisanti, Massimo, Varbella, Ferdinando, de Cosmo, Salvatore, Trevisan, Roberto, Bellotti, Sandro, Di Pasquale, Giuseppe, Bongo, Angelo S, Uguccioni, Massimo, Mannucci, Edoardo, Mauro, Ciro, Ragonese, Mauro, Fresco, Claudio, Turturo, Maurizio, Marcucci, Rossella, Lievano Triana, Manuel J, Arana, Camilo, Accini, Jose, Botero, Rodrigo, Muzyk-Osikowicz, Marlena, Dada, Fredy T, Vallejo, Gregorio S, Manzur, Fernando, Isaza, Daniel, Molina, Dora, Mesa, Juan G, Quintero, Alvaro, Nyman, Kai, Mäkelä, Jyrki, Strand, Jorma, Nieminen, Sakari, Taurio, Jyrki, Kuusela, Matti, Valle, Timo, Pietilä, Mikko, Kekki, Sakari, Strandberg, Timo, Klutstein, Marc, Greenberg, Gabriel, Rozenman, Yoseph, Chorin, Ehud, Roguin, Ariel, Lewis, Basil, Bashkin, Amir, Tan, Edgar, Prado, Jose P, Ferrolino, Arthur, Babilonia, Noe, Barbas, Benny, Matiga, Generoso, Coching, Raul M, Drexel, Heinz, Brath, Helmut, Schnack, Christoph, Hanusch, Ursula, Fließer-Görzer, Evelyn, Paulweber, Bernhard, Ebenbichler, Christoph, Prager, Rudolf, Huber, Kurt, Wolzt, Michael, Auer, Johann, Berger, Rudolf, Schernthaner, Gerit-Holger, Stanciulescu, Gabriela, Creteanu, Mihai, Spiridon, Marilena, Dobreanu, Viorica, Vinereanu, Dragos, Iosipescu, Laura C, Istratoaie, Octavian, Coman, Ioan, Militaru, Constantin, Cinteza, Mircea, Bhatt, Deepak L, Fox, Kim, Harrington, Robert A, Leiter, Lawrence A, Mehta, Shamir R, Simon, Tabassome, Andersson, Marielle, Himmelmann, Anders, Steg, Philippe G, Diaz, Rafael, Amerena, John, Huber, Kurt, Sinnaeve, Peter R, Nicolau, José C, Kerr Saraiva, José F, Petrov, Ivo, Leiter, Lawrence A, Mehta, Shamir R, Corbalán, Ramón, Ge, Junbo, Zhao, Qiang, Botero, Rodrigo, Widimský, Petr, Kristensen, Steen D, Hartikainen, Juha, Danchin, Nicolas, Darius, Harald, Tse, Hung F, Kiss, Robert G, Pais, Prem, Lev, Eli, de Luca, Leonardo, Goto, Shinya, Ramos López, Gabriel A, Cornel, Jan H, Kontny, Frederic, Medina, Felix, Babilonia, Noe A, Opolski, Grzegorz, Vinereanu, Dragos, Zateyshchikov, Dmitry A, Ruda, Mikhail, Elamin, Omer, Kovář, František, Dalby, Anthony J, Jeong, Myung H, Bueno, Héctor, James, Stefan K, Chiang, Chern-En, Tresukosol, Damras, Ongen, Zeki, Ray, Kausik K, Parkhomenko, Alexander, McGuire, Darren K, Kosiborod, Mikhail N, Nguyen, Tuan Q, Andersson, Marielle, Chen, Jersey, Himmelmann, Anders, Leonsson-Zachrisson, Maria, and Ridderstråle, Wilhelm

Abstract

Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor.

Published
2019
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43. Efficacy and safety of ticagrelor for long-term secondary prevention of atherothrombotic events in relation to renal function: insights from the PEGASUS-TIMI 54 trial

Author

Magnani, Giulia, primary, Storey, Robert F., additional, Steg, Gabriel, additional, Bhatt, Deepak L., additional, Cohen, Marc, additional, Kuder, Julia, additional, Im, Kyungah, additional, Aylward, Philip, additional, Ardissino, Diego, additional, Isaza, Daniel, additional, Parkhomenko, Alexander, additional, Goudev, Assen R., additional, Dellborg, Mikael, additional, Kontny, Frederic, additional, Corbalan, Ramon, additional, Medina, Felix, additional, Jensen, Eva C., additional, Held, Peter, additional, Braunwald, Eugene, additional, Sabatine, Marc S., additional, and Bonaca, Marc P., additional

Published
2015
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44. ACTIVATED LEUKOCYTE CELL ADHESION MOLECULE (ALCAM) AND OUTCOMES IN ACUTE CORONARY SYNDROMES: A PLATO BIOMARKER SUBSTUDY

Author

Wallentin, Lars, primary, Michelsen, Annika E., additional, Aukrust, Pål, additional, Becker, Richard, additional, Bertilsson, Maria, additional, Budaj, Andrzej, additional, Cornel, Jan, additional, Himmelmann, Anders, additional, Husted, Steen, additional, Siegbahn, Agneta, additional, Storey, Robert, additional, Kontny, Frederic, additional, and Ueland, Thor, additional

Published
2015
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45. BIOMARKERS FOR PREDICTION OF OUTCOMES IN REVASCULARIZED PATIENTS WITH NON-ST-ELEVATION ACUTE CORONARY SYNDROME: A PLATO SUBSTUDY

Author

Lindholm, Daniel, primary, James, Stefan, additional, Bertilsson, Maria, additional, Cannon, Christopher, additional, Giannitsis, Evangelos, additional, Harrington, Robert, additional, Himmelmann, Anders, additional, Kontny, Frederic, additional, Siegbahn, Agneta, additional, Steg, Philippe, additional, Velders, Matthijs, additional, Weaver, W. Douglas, additional, and Wallentin, Lars, additional

Published
2014
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46. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO) : a randomised double-blind study

Author

Cannon, Christopher P., Harrington, Robert A., James, Stefan, Ardissino, Diego, Becker, Richard C., Emanuelsson, Håkan, Husted, Steen, Katus, Hugo, Keltai, Matyas, Khurmi, Nardev S., Kontny, Frederic, Lewis, Basil S., Steg, Philippe Gabriel, Storey, Robert F., Wojdyla, Daniel, Wallentin, Lars, Cannon, Christopher P., Harrington, Robert A., James, Stefan, Ardissino, Diego, Becker, Richard C., Emanuelsson, Håkan, Husted, Steen, Katus, Hugo, Keltai, Matyas, Khurmi, Nardev S., Kontny, Frederic, Lewis, Basil S., Steg, Philippe Gabriel, Storey, Robert F., Wojdyla, Daniel, and Wallentin, Lars

Abstract

BACKGROUND: Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopidogrel in such patients. METHODS: At randomisation, an invasive strategy was planned for 13 408 (72.0%) of 18 624 patients hospitalised for acute coronary syndromes (with or without ST elevation). In a double-blind, double-dummy study, patients were randomly assigned in a one-to-one ratio to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300-600 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for 6-12 months. All patients were given aspirin. The primary composite endpoint was cardiovascular death, myocardial infarction, or stroke. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00391872. FINDINGS: 6732 patients were assigned to ticagrelor and 6676 to clopidogrel. The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group (569 [event rate at 360 days 9.0%] vs 668 [10.7%], hazard ratio 0.84, 95% CI 0.75-0.94; p=0.0025). There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (691 [11.6%] vs 689 [11.5%], 0.99 [0.89-1.10]; p=0.8803) or severe bleeding, as defined according to the Global Use of Strategies To Open occluded coronary arteries, (198 [3.2%] vs 185 [2.9%], 0.91 [0.74-1.12]; p=0.3785). INTERPRETATION: Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned.

Published
2010
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47. Effects of telmisartan on office and 24-hour ambulatory blood pressure: an observational study in hypertensive patients managed in primary care

Author

Kontny,Frederic, Risanger, Bye,Arne, Arnesen,Oyvind, Johansen,Erik, Kontny,Frederic, Risanger, Bye,Arne, Arnesen,Oyvind, and Johansen,Erik

Abstract

Frederic Kontny1, Terje Risanger2, Arne Bye3, Øyvind Arnesen4, Odd Erik Johansen4 for the TELMIMORE Study Investigators51Dept of Cardiology, Volvat Medical Centre, Oslo, Norway; 2Prinsdal Health Centre, Oslo, Norway; 3Frosta Health Centre, Frosta, Norway; 4Medical Department, Boehringer-Ingelheim Norway KS, Asker, Norway; 5The TELMIMORE Study Investigators are listed at the end of the paperPurpose: Although elevated blood pressure (BP) predicts future cardiovascular events, recommended BP targets often is not reached in the general community. In a clinical real-life setting we evaluated BP impact and tolerability of the angiotensin-II receptor blocker telmisartan in patients with essential hypertension.Patients and methods: Patients in this observational study not at target BP started or switched to telmisartan monotherapy (40 or 80 mg) or a fixed-dose combination of telmisartan and hydrochlorothiazide (HCT) 80 mg/12.5 mg. Office and 24-hour ambulatory BP (AMBP) were measured before and after 8 weeks of treatment and physicians reported perceived drug efficacy and tolerability as “Very good”, “Good”, “Moderate” or “Bad”.Results: 100 patients (34% female, 60 years, BMI 29.4 kg/m2, mean office BP 159/92 mmHg) of whom 38% were treatment naïve and 30%, 17%, 9% and 6% respectively were on 1, 2, 3 or 4 BP-lowering drugs, completed 8 weeks of treatment. The proportion of patients with office BP < 140/90 mmHg increased from 3% to 54% for systolic (P < 0.001), 38% to 75% for diastolic (P < 0.001), and 2% to 45% for systolic and diastolic BP (P < 0.001). A significant effect on BP levels was seen in patients being either treatment naïve or on 1 to 3 BP-lowering drugs at study entry, whereas no BP improvement occurred in those who switched from 4 drugs. Overall, mean 24-hour AMBP was reduced from 141/85 to 131/79 mmHg (P < 0.001). Drug

Published
2010

49. Quantitative T-wave analysis predicts 1 year prognosis and benefit from early invasive treatment in the FRISC II study population.

Author

Jacobsen, Michael D, Wagner, Galen S, Holmvang, Lene, Kontny, Frederic, Wallentin, Lars, Husted, Steen, Swahn, Eva, Ståhle, Elisabeth, Steffensen, Rolf, Clemmensen, Peter, Jacobsen, Michael D, Wagner, Galen S, Holmvang, Lene, Kontny, Frederic, Wallentin, Lars, Husted, Steen, Swahn, Eva, Ståhle, Elisabeth, Steffensen, Rolf, and Clemmensen, Peter

Published
2005

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