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Your search keyword '"Gonzalez Juanatey, Jose Ramon"' showing total 10 results
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10 results on '"Gonzalez Juanatey, Jose Ramon"'

1. Mid-range left ventricular ejection fraction: Clinical profile and cause of death in ambulatory patients with chronic heart failure.

Author

Pascual-Figal DA, Ferrero-Gregori A, Gomez-Otero I, Vazquez R, Delgado-Jimenez J, Alvarez-Garcia J, Gimeno-Blanes JR, Worner-Diz F, Bardají A, Alonso-Pulpon L, Gonzalez-Juanatey JR, and Cinca J

Subjects
Aged, Aged, 80 and over, Cause of Death, Chronic Disease, Cohort Studies, Female, Follow-Up Studies, Heart Failure diagnosis, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Registries, Ambulatory Care trends, Heart Failure mortality, Heart Failure physiopathology, Ventricular Function, Left physiology
Abstract

Background: The intermediate group of patients with heart failure (HF) and mid-range left ventricular ejection fraction (HFmrEF) may constitute a specific phenotype, but a direct evidence is lacking. This study aimed to know whether this HF category is accompanied by a particular clinical phenotype and prognosis., Methods and Results: This study includes 3446 ambulatory patients with chronic HF from two national registries. According to EF at enrollment, patients were classified as reduced (HFrEF, <40%), mid-range (HFmrEF, 40-49%) or preserved (HFpEF, ≥50%). Patients were followed-up for a median of 41months and the specific cause of death was prospectively registered. Patients with HFmrEF represented 13% of population and they exhibited a phenotype closer to HFrEF, except for a higher rate of coronary revascularization and diabetes, and a less advanced HF syndrome. The observed all-cause mortality was higher among HFrEF (33.0%), and similar between HFmrEF (27.8%) and HFpEF (28.0%) (p=0.012); however, the contribution of each cause of death differed significantly between categories (p<0.001). After propensity score matching, the risk of cardiovascular death, HF death or sudden cardiac death did not differ between HFmrEF and HFrEF in paired samples; however, patients with HFmrEF were at higher risk of cardiovascular death (sHR 1.71, 95% CI 1.13-2.57, p=0.011) and sudden cardiac death (sHR 2.73, 95% CI 1.07-6.98, p=0.036) than patients with HFpEF., Conclusions: Patients in the intermediate category of HFmrEF conform a phenotype closer to the clinical profile of HFrEF, and associated to higher risk of sudden cardiac death and cardiovascular death than patients with HFpEF., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Published
2017
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2. Why and when do patients with heart failure and normal left ventricular ejection fraction die? Analysis of >600 deaths in a community long-term study.

Author

Grigorian-Shamagian L, Otero Raviña F, Abu Assi E, Vidal Perez R, Teijeira-Fernandez E, Varela Roman A, Moreira Sayagues L, and Gonzalez-Juanatey JR

Subjects
Aged, Aged, 80 and over, Death, Sudden, Cardiac epidemiology, Echocardiography, Female, Follow-Up Studies, Heart Failure diagnostic imaging, Heart Failure physiopathology, Hospitalization statistics & numerical data, Humans, Male, Middle Aged, Myocardial Infarction diagnostic imaging, Myocardial Infarction mortality, Myocardial Infarction physiopathology, Spain, Systole physiology, Ventricular Dysfunction, Left diagnostic imaging, Ventricular Dysfunction, Left physiopathology, Cause of Death, Heart Failure mortality, Ventricular Dysfunction, Left mortality, Ventricular Function, Left physiology
Abstract

Background: The aim of the study was to examine the causes of the death of patients with heart failure (HF) and evaluate the differences in this respect between patients with and without depression of left ventricular ejection fraction (LVEF)., Method: All patients hospitalized with HF between 1995 and 2002 in the cardiology service of a tertiary hospital were assessed. LVEF was evaluated by echocardiography during hospitalization and was considered normal when it was > or =50%. After a mean follow-up time of 3.7 +/- 2.8 years, 615 cases had terminated in death., Results: The most common cause was refractory HF, both in the whole group (39%) and in both the subgroups defined with respect to LVEF (normal and depressed). There was no statistically significant difference between the normal and depressed subgroups as regard the distribution of deaths, although the depressed group showed a somewhat greater incidence of sudden death (21% as against 16% in the normal group) and a somewhat smaller incidence of death due to refractory HF (37% as against 47%). However, in the depressed LVEF group, the cumulative risk of death due to acute myocardial infarction in the first 1.5 years first increased rapidly and then more slowly, whereas the reverse pattern was held in the normal left ventricular systolic function group, in which it was the cumulative risks of death from noncardiovascular or vascular noncardiac causes that initially increased more rapidly than later., Conclusions: The spectrum of causes of death among patients with HF who have been hospitalized is independent of LVEF in the long term. In the short term, there are differences between patients with normal LVEF and depressed LVEF as regard the dynamics of the risks of death from acute myocardial infarction, noncardiac vascular causes, and noncardiovascular causes. These results may help orient the short-term and long-term management of HF, especially for patients with normal LVEF, for whom there is still no well-established consensus strategy.

Published
2008
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3. Association of blood pressure and its evolving changes with the survival of patients with heart failure.

Author

Grigorian-Shamagian L, Gonzalez-JuAnatey JR, Vazquez R, Cinca J, Bayes-Genis A, Pascual D, Fernandez-Palomeque C, Bardaji A, Almendral J, Nieto V, Macaya C, Jimenez RP, and de Luna AB

Subjects
Adrenergic beta-Antagonists therapeutic use, Aged, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Blood Pressure drug effects, Calcium Channel Blockers therapeutic use, Death, Sudden, Cardiac etiology, Diuretics therapeutic use, Female, Follow-Up Studies, Heart Arrest etiology, Heart Failure drug therapy, Humans, Hypertrophy, Left Ventricular physiopathology, Hypotension chemically induced, Hypotension physiopathology, Male, Middle Aged, Mineralocorticoid Receptor Antagonists therapeutic use, Prospective Studies, Spironolactone therapeutic use, Stroke Volume drug effects, Survival Rate, Ventricular Function, Left drug effects, Blood Pressure physiology, Heart Failure physiopathology
Abstract

Objective: The association between low blood pressure (BP) levels and increased mortality has been established in several studies of heart failure (HF). Although many drugs administered to these patients decrease BP, the relationship between changes in BP and survival has not been investigated. Nor have previous analyses distinguished among different forms of death. We investigated the influence of baseline BP and changes in BP during a 1-year period on the survival of patients with HF, distinguishing among sudden cardiac death, nonsudden cardiac death, and noncardiac death. We also identified the possible relationship with the baseline values of and changes in other clinical and treatment variables, including pharmacologic treatments., Method and Results: A total of 1062 patients with chronic HF included in the Spanish National Registry of Sudden Death (mean age of 64.5 +/- 11.8 years, 72% were men, and 21% were in New York Heart Association class III with a mean left ventricular ejection fraction of 36.7% +/- 14.2%) were prospectively investigated for a mean of 1.9 +/- 0.6 years. A multivariable Cox proportional hazards model adjusting for clinical and therapeutic variables showed an independent association between low baseline systolic blood pressure (SBP) and nonsudden cardiac death (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.93-0.98), but changes in SBP during the following year did not influence survival, regardless of the baseline SBP level (P = .55). Contrariwise, baseline diastolic BP was not associated with mortality, but an increase in diastolic BP during the following year showed a borderline independent significant association with lower nonsudden cardiac death (HR 0.90, 95% CI 0.82-1.00). Treatment with angiotensin-converting enzyme inhibitors or beta-blockers at baseline was also associated with lower nonsudden cardiac mortality, as was an increase in left ventricular ejection fraction during the following year (HR 0.69, 95% CI 0.51-0.93; P = .015)., Conclusion: Among patients with stable HF, low SBP is associated with a greater risk of nonsudden cardiac death. The change in SBP during a 1-year period has no prognostic value. Because the beneficial effects of drugs associated with increased survival (in this study, angiotensin-converting enzyme inhibitors and beta-blockers) thus seem to be independent of their effects on BP, changes in BP should probably not influence the decision to use such drugs or continue their administration.

Published
2008
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4. Acute pulmonary edema in patients with decompensated heart failure. Role of underlying cardiopathy on the prognosis.

Author

Grigorian Shamagian L, Roman AV, Ramos PM, Acuña JM, Veloso PR, and Gonzalez-Juanatey JR

Subjects
Aged, Aged, 80 and over, Female, Heart Failure pathology, Humans, Male, Middle Aged, Risk Factors, Survival Rate, Heart Failure etiology, Heart Failure mortality, Pulmonary Edema etiology
Abstract

Aims: To investigate the impact of acute pulmonary edema (APE) on the prognosis of patients hospitalized with congestive heart failure (CHF) and if the underlying cardiopathy influences the survival of these patients., Method and Results: All patients admitted to the cardiology department of a tertiary hospital with CHF between 1991 and 2002 were included in the present study. APE was diagnosed in 176 of 1659 patients. 60.2% of them were of ischaemic etiology, 48.6% and 42.9% of hypertensive and valvular origin, respectively. Survival analysis carried out in April 2003 has shown that APE patients have higher mortality rates, with a median survival of 3.1 years as against 4.8 years. This difference was due only to the behaviour of patients with ischaemic CHF as among patients with non-ischaemic CHF, the difference in median survival between patients with and without APE was insignificant. Within the APE group the survival of ischaemic patients was lower than that of non-ischaemic (median survival of 2.3 years vs 4.5 years, respectively). The difference was more pronounced between APE patients with CHF of ischaemic and hypertensive origin (median survival of 5.6 years for the latter). Among patients without APE, there was no significant difference between different etiological groups., Conclusion: In this study we found that the survival time of CHF patients is significantly shortened by the concurrence of APE and ischaemic etiology but not by either of these factors without the other.

Published
2007
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5. Left atrial enlargement and NT-proBNP as predictors of sudden cardiac death in patients with heart failure.

Author

Bayes-Genis A, Vazquez R, Puig T, Fernandez-Palomeque C, Fabregat J, Bardají A, Pascual-Figal D, Ordoñez-Llanos J, Valdes M, Gabarrús A, Pavon R, Pastor L, Gonzalez Juanatey JR, Almendral J, Fiol M, Nieto V, Macaya C, Cinca J, and Bayes de Luna A

Subjects
Aged, Cardiomegaly blood, Female, Heart Failure blood, Humans, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Risk Assessment, Sensitivity and Specificity, Cardiomegaly epidemiology, Death, Sudden, Cardiac epidemiology, Heart Atria, Heart Failure epidemiology, Natriuretic Peptide, Brain blood, Peptide Fragments blood
Abstract

Aims: The identification of valuable markers of sudden cardiac death (SCD) in patients with established HF remains a challenge. We sought to assess the value of clinical, echocardiographic and biochemical variables to predict SCD in a consecutive cohort of patients with heart failure (HF) due to systolic dysfunction., Methods: A cohort of 494 patients with established HF had baseline echocardiographic and NT-proBNP measurements and were followed for 942+/-323 days., Results: Fifty patients suffered SCD. Independent predictors of SCD were indexed LA size>26 mm/m2 (HR 2.8; 95% CI 1.5-5.0; p=0.0007), NT-proBNP>908 ng/L (HR 3.1; 95% CI 1.5-6.7; p=0.003), history of myocardial infarction (HR 2.3; 95% CI 1.3-4.1; p=0.007), peripheral oedema (HR 2.1; 95% CI 1.1-3.9; p=0.02), and diabetes mellitus (HR 1.9; 95% CI 1.1-3.3; p=0.03). NYHA functional class, left ventricular ejection fraction and glomerular filtration rate were not independent predictors of SCD in this cohort. Notably, the combination of both LA size>26 mm/m2 and NT-proBNP>908 ng/L increased the risk of SCD (HR 4.3; 95% CI 2.5-7.6; p<0.0001). At 36 months, risk of SCD in patients with indexed LA size26 mm/m2 and NT-proBNP>908 ng/L reached 25% (p<0.0001)., Conclusions: Among HF patients, indexed LA size and NT-proBNP levels are more useful to stratify risk of SCD than other clinical, echocardiographic or biochemical variables. The combination of these two parameters should be considered for predicting SCD in patients with HF.

Published
2007
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6. Angiotensin-converting enzyme inhibitors prescription is associated with longer survival among patients hospitalized for congestive heart failure who have preserved systolic function: a long-term follow-up study.

Author

Grigorian Shamagian L, Roman AV, Ramos PM, Veloso PR, Bandin Dieguez MA, and Gonzalez-Juanatey JR

Subjects
Age Factors, Aged, Anemia mortality, Female, Follow-Up Studies, Hospitalization, Humans, Male, Multivariate Analysis, Prospective Studies, Spain epidemiology, Stroke Volume, Survival Rate, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Heart Failure drug therapy, Heart Failure mortality
Abstract

Background: The use of inhibitors of angiotensin-converting enzyme (ACE) is strongly indicated by a diagnosis of congestive heart failure (CHF) with deteriorated systolic function (SF), but their effects on patients with CHF but no systolic deterioration have not been clarified. We focused this study on the evaluation of the influence of ACE inhibitors on survival among CHF patients with preserved SF, but also determined the effect of these drugs on the prognosis of our patients with deteriorated SF., Method and Results: We studied 416 patients, aged 72.7 +/- 10.2 years, who between January 1, 1991, and December 31, 2001, were admitted to the cardiology service of a tertiary hospital for CHF and who fulfilled the requirements that left ventricular SF that had been evaluated echocardiographically during hospitalization was preserved and that data were available on medication at the time of their release from hospital. Two hundred four patients (49.0%) were men, 250 (60.8%) were hypertensive, and, in 171 (41.1%) cases, ischemic cardiopathy was the primary cause of the CHF. ACE inhibitors were prescribed to 210 patients (50.5%) on hospital release. Kaplan-Meier survival curve analysis showed that, among patients with preserved SF, a longer survival was associated with ACE inhibitors use (mean survival 6.14 years as compared with 4.57 years in the control group, P < .001; adjusted hazard ratio = 0.63, P = .012). Similar results were obtained in CHF patients with deteriorated SF in whom those taking ACE inhibitors had significantly longer life with mean survival 6.42 years compared with 5.03 years in the control group (P < .001; adjusted hazard ratio = 0.62, P = .001)., Conclusion: ACE inhibitors prescription is associated with a better prognosis of patients with CHF and preserved SF.

Published
2006
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7. The death rate among hospitalized heart failure patients with normal and depressed left ventricular ejection fraction in the year following discharge: evolution over a 10-year period.

Author

Grigorian Shamagian L, Gonzalez-Juanatey JR, Roman AV, Acuña JM, and Lamela AV

Subjects
Aged, Female, Heart Failure physiopathology, Hospitalization, Humans, Male, Prevalence, Risk Factors, Stroke Volume, Survival Rate, Ventricular Dysfunction, Left physiopathology, Heart Failure mortality, Hospital Mortality, Ventricular Dysfunction, Left mortality
Abstract

Aims: To investigate whether changes in clinical characteristics and treatment strategies between 1991 and 2001 have had an impact on the survival of patients hospitalized with congestive heart failure (CHF) and whether those with normal left ventricular ejection fraction (LVEF> or =50%) differ in this respect from those with depressed LVEF., Methods and Results: We studied 1482 patients who had been admitted to the Cardiology Service of a tertiary Spanish hospital in the last 10 years with CHF. Among the 1110 for whom LVEF was evaluated, the prevalence of normal LVEF rose from 37% in the period 1991-96 (Period 1) to 47% in the period 2000-2001 (Period 3). The intensity of both diagnostic and therapeutic measures also increased during this 10-year period. The 1-year survival rate remained virtually unchanged in the whole group of patients, being 82, 84, and 82% in Periods 1, 2 (1997-99), and 3, respectively, even though the prognosis of patients with depressed LVEF (<50%) improved significantly, with 1-year survival rates of 76, 77, and 84% in Periods 1, 2, and 3, respectively; the normal LVEF group had decreasing 1-year survival rates of 88, 86, and 81% in Periods 1, 2, and 3, respectively, although the increased risk of death was not statistically significant., Conclusion: Although in our centre the death rate among hospitalized CHF patients with depressed LVEF during the first year after discharge has tended to fall over the past 10 years, application of current clinical guidelines has led to no such decrease for patients with normal LVEF. This situation points to a need to reconsider the diagnostic and therapeutic strategy to be employed with this latter group of patients.

Published
2005
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8. Influence of diabetes on the survival of patients hospitalized with heart failure: a 12-year study.

Author

Varela-Roman A, Grigorian Shamagian L, Barge Caballero E, Mazon Ramos P, Rigueiro Veloso P, and Gonzalez-Juanatey JR

Subjects
Aged, Female, Heart Failure physiopathology, Humans, Hypertension epidemiology, Male, Middle Aged, Myocardial Ischemia mortality, Prospective Studies, Stroke Volume, Survival Analysis, Diabetic Angiopathies mortality, Heart Failure mortality
Abstract

Aim: To investigate the influence of diabetes mellitus (DM) on the prognosis of heart failure (HF) patients, focussing specifically on aetiology and patients with preserved left ventricular systolic function (LVSF), which to date has not been fully investigated., Method and Results: 1659 Patients hospitalized for HF between 1991 and 2002 in the Cardiology Department of a tertiary hospital, aged 69+/-12 years, 60% male were studied prospectively. Arterial hypertension was present in 54% of patients, DM in 26% and ischaemic cardiomyopathy in 51%. A survival analysis performed in April 2003 showed that DM worsens the prognosis of the whole group (median survival (MS): 3.6 vs. 5.4 years; p<0.001), of ischaemic and non-ischaemic patients (MS: 3.8 vs. 4.9 years; p=0.13 and 3.6 vs. 6.0 years; p<0.001, respectively). A similar effect of DM was shown in patients with preserved LVSF (MS: 3.8 vs. 5.8 years; p=0.03) and in patients with impaired LVSF (3.6 vs. 6.3 years; p<0.0001)., Conclusion: DM increases mortality among HF patients with preserved and impaired LVSF and those without ischaemic cardiomyopathy.

Published
2005
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9. Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

Author

Butler, Amy, Elmersson, Micael, Egilsson, Arnor, Borjesson, Ulf, Svard, Gunnar, Liu, Bo, Lindh, Anders, Olsson, Lars-Bertil, Gustaysson, Mikael, Andersson, Lars, Benson, Lars, Bothin, Claes, Hajimirsadeghi, Ali, Martinsson, Bjorn, Ericsson, Marianne, Ohlsson, Ake, Lindvall, Hakan, Svensson, Peter, Thorne, Katarina, Handel, Hans, Platonov, Pyotr, Bernsten, Fredrik, Timberg, Ingar, Crisby, Milita, Karlsson, Jan-Erik, Andersson, Agneta, Malmqvist, Lennart, Engdahl, Johan, Thulin, Jorgen, Hot-Bjelak, Aida, Jensen, Steen, Debrunner, Johann, Beer, Juerg H., Shah, Dipen, Rudyk, Iurii, Tseluyko, Vira, Karpenko, Oleksandr, Zhurba, Svitlana, Kraiz, Igor, Parkhomenko, Oleksandr, Kupnovytska, Iryna, Seredyuk, Nestor, Mostovoy, Yuriy, Ushakov, Oleksiy, Koval, Olena, Kovalskiy, Igor, Svyshchenko, Yevgeniya, Sychov, Oleg, Stanislavchuk, Mykola, Tykhonova, Susanna, Fushtey, Ivan, Murdoch, Will, Chauhan, Naresh, Goodwin, Daryl, Lumley, Louise, Patel, Ramila, Saunders, Philip, Wong, Bennett, Patel, Niranjan, Jhittay, P., Ross, Andrew, Kainth, M. S., Ladha, Karim, Douglas, Kevin, Pickavance, Gill, McDonnell, Joanna, Handscombe, Laura, Gooding, Trevor, Wagner, Helga, Bradshaw, Colin, Bromham, Catherine, Jones, Kevin, Suryani, Shoeb, Coates, Richard, Sarai, Bhupinder, Willcock, W., Sircar, S., Cairns, John, Gilliand, A., Bilas, Roman, Strieder, E., Hutchinson, Peter, Wakeman, Anne, Stokes, Michael, Kirby, Graham, Vishwanathan, Bhaskhar, Vormann, Reinhold, Mueller, Thomas, Mayer, Peter, Horstmeier, Uwe, Eissing, Volker, Hey, Heinz, Leuchtgens, Heinz, Lilienweiss, Volker, Mueller, Heiner, Schubert, Christian, Lauer, Hellmann, Buchner, Thomas, Brauer, Gunter, Kamin, Susanne, Mueller, Karsten, Baumbach, Sylvia, Abdel-Qader, Muwafeg, Ebert, Hans-Holger, Schwencke, Carsten, Bernhardt, Peter, Karolyi, Laszlo, Sievers, Britta, Haverkamp, Wilhelm, Roehnisch, Jens-Uwe, Vertes, Andras, Szantai, Gabor, Menke, Holger, Matoltsy, Andras, Kanakaridisz, Nikosz, Boda, Zoltan, Kis, Erno, Gaszner, Balazs, Juhasz, Ferenc, Kamogawa, Yasuyuki, Fournier, Pierre-Yves, Muller, Jean-Joseph, Marquand, Andre, Delarche, Nicolas, Bantwal, Ganapathi, Faes, Dirk, Verstraete, Stefan, Dominguez, Helena, Topsakal, Ramazan, Centurion, Nestor, Alfredo Sinisi, Victor, Minc, Piotr, Nagy, Andras, Bilo, Grzegorz, Bongiorni, Maria Grazia, Bird, Nigel, Paul, Carolyn, Wadeson, Paul, Hargreaves, Nick, Kostenko, Victor, Tercedor Sanchez, Luis, Tranche Iparraguirre, Salvador, Jimenez Gonzalez, Mercedes, Herreros Melenchon, Juan, Stalby, Per, Yagensky, Andriy, Cameron, Alex, Jacobs, Polly, Juhasz, Gizella, Kancz, Sandor, Laszlo, Zoltan, May, Zsolt, Astridge, Penny, Loghdey, Rehana, Quick, Annette, Yang, Ping, Chen, Yingmin, He, Shenghu, Wang, Yong, Fu, Guosheng, Li, Xin, Wu, Tongguo, Cheng, Xiaoshu, Yan, Xiaowei, Zhao, Ruiping, Chen, Moshui, Xiong, Longgen, Chen, Ping, Jiao, Yang, Guo, Ying, Xue, Li, Yang, Zhiming, Jadhavm, Praveen, Merkely, Bela, Noon, Ebrahim, Habon, Tamas, Polgar, Peter, Szalai, Gabriella, Vangel, Sandor, Sarma, Raghava, Kulkarni, Govind, Engelthaler, Gabriella, Ferenczi, Judit, Chandwani, Prakash, Pothiwala, Rasesh Atulbhai, Purayil, Mohanan Padinhare, Chawla, Kamaldeep, Verheugt, Freek W. A., Ambrosio, Giuseppe, Atar, Dan, Bassand, Jean-Pierre, Costabel, Juan Pablo, Goldhaber, Samuel Z., Goto, Shinya, Egyutt, Mihaly, Martini, Giuliana, Cristina, Leone Maria, Tirafern, Eros, Santoro, Rita, Testa, Sophie, Di Minno, Giovanni, Moia, Marco, Caimi, Teresa Maria, Tessitori, Maria, Cappelli, Roberto, Accogli, Michele, Mariani, Antonio, Feola, Mauro, Raisaro, Arturo, Fattore, Luciano, Mauric, Andrea, Germini, Fabrizio, Tedeschi, Luca, Settimi, Maria, Nicoli, Sergio, Ricciarini, Paolo, Argena, Antonio, Ronchini, Paolo, Bulla, Claudio, Tradati, Filippo, Volpe, Massimo, Avino, Maria D., Seven, Silva, Capucci, Alessandro, Lodigiani, Corrado, Salomone, Enrico, Serviddio, Gaetano, Tondo, Claudio, Golino, Paolo, Mazzone, Carmine, Iacopino, Saverio, Ruiter, J. H., Lucassen, Andreas, Adriaansen, Henk, Bongaerts, Maarten, Pieterse, Mathijs, van Guldener, Coen, Herrman, Johannes, Nierop, S. H. K. P. R., Hoogslag, Pieter, Hermans, Walter, Groenemeijer, B. E., Terpstra, W., Buiks, Cees, Boersma, L. V. A., Berge, Eivind, Sirnes, Per Anton, Gjertsen, Erik, Hole, Torstein, Erga, Knut, Hallaraker, Arne, Skjelvan, Gunnar, Ostrem, Anders, Ghezai, Beraki, Svilaas, Arne, Christersson, Peter, Oien, Torbjorn, Henrichsen, Svein Hoegh, Otterstad, Jan Erik, Berg-Johansen, Jan, Gieroba, Andrzej, Biedrzycka, Malgorzata, Ogorek, Michal, Wozakowska-Kaplon, Beata, Loboz-Grudzien, Krystyna, Jaroslaw, Jaroslaw, Supinski, Wieslaw, Kuzniar, Jerzy, Zaluska, Roman, Hiczkiewicz, Jaroslaw, Swiatkowska-Byczynska, Lucyna, Kucharski, Lech, Gruchala, Marcin, Olszewski, Maciej, Kania, Grzegorz, Krzciuk, Malgorzata, Lajkowski, Zbigniew, Ostrowska-Pomian, Bozenna, Lewczuk, Jerzy, Zinka, Elzbieta, Karczmarczyk, Agnieszka, Chmielnicka-Pruszczynska, Malgorzata, Wozniak-Skowerska, Iwona, Opolski, Grzegorz, Bronisz, Marek, Ogorek, Marcin, Glanowska, Grazyna, Ruszkowski, Piotr, Skonieczny, Grzegorz, Sciborski, Ryszard, Okopien, Boguslaw, Kukla, Piotr, Galbas, Krzysztof, Cymerman, Krzysztof, Jurowiecki, Jaroslaw, Miekus, Pawel, Myszka, Waldemar, Mazur, Stanislaw, Lysek, Roman, Baszak, Jacek, Rusicka-Piekarz, Teresa, Raczak, Grzegorz, Domanska, Ewa, Nessler, Jadwiga, Catanchin, Andrei, Colquhoun, David, Kiat, Hosen, Eccleston, David, French, John, Ayres, Bronte, Blombery, Peter, Phan, Thanh, Rogers, James, O'Donnell, David, Cheol, Sang, Carroll, Patrick, Starmer, Greg, Arstall, Margaret, Binnekamp, Maurits, Lee, Astin, Luton, Robert, Gupta, Milan, Pandey, Amritanshu Shekhar, Cheung, Stephen, Leader, Rolland, Beaudry, Philippe, Ayala-Paredes, Felix, Berlingieri, Joseph, Heath, John, Poirier, Germain, du Preez, Miranda, Schweitzer, Bradley, Nadeau, Reginald, Dhillon, Ripple, Hruczkowski, Tomasz, Lavoie, Andrea, Parkash, Ratika, Cha, James, Coutu, Benoit, MacDonald, Paul, Ramjattan, Brian, Bonet, Jorge, Vizel, Saul, Angaran, Paul, Fikry, Sameh, Mowafy, Ahmed, Katta, Azza, Tawfik, Mazen, Nawar, Moustafa, Sobhy, Mohamed, Abou Seif, Seif Kamal, Khairy, Tarek, Abd El-Aziz, Ahmed, Taha, Nasser, Reda, Ashraf, Elbahry, Atef, Setiha, Mohamed, El Din, Mohamed Gamal, Elkhadem, Magdi, El-Etreby, Adel, Kettles, David, Bayat, Junaid, Siebert, Heidi, Horak, Adrian, Kelfkens, Ynez, Garda, Riaz, Pillay, Thayabran, Guerra, Michele, van Zyl, Louis, Theron, Hendrik, Murray, Andrew, Louw, Rikus, Greyling, Deon, Mntla, Pindile, Ismail, Siddique, Ahmed, Fayzal, Engelbrecht, Johannes, Maharajh, Shambu, Oosthuysen, Wessel, Ueckermann, Veronica, Al Naeemi, Abdullah, Yousef, Ghazi, Bazargani, Nooshin, Alomairi, Munther, Maruthanayagam, Rajan, Singh, Rupesh, Naguib, Ahmed, Ibrahim, Mohamed, Agrawal, Amrish, Nathani, Mukesh, Esheiba, Ehab M., Wassef, Adel, Gupta, Rajeev, Cox, Michael, Beach, Scott, Duffy, Peter, Falkowski, Stephen, Ferrick, Kevin, Franco, Miguel, Kutayli, W. Michael, Sharma, Niraj, Wilson, Vance, Miller, Stephen, Alberts, Mark, Blumberg, Edwin, Canosa, Roddy, Gutowski, Ted, Ison, Rodney, Garcia, Jorge, Mullen, Paul, Noveck, Howard, Rama, Pamela, Reddy, Rajneesh, Williams, Marcus, Nishijima, Daniel, Ferdinand, Keith, Hague, Ihsan, Mendelson, Robert, Pitta, Sridevi, Theodoro, Daniel, Treasure, Charles, Moustafa, Moustafa, Cader, Cas, Pharr, Walter, Oropallo, Alisha, Platt, George, Gujral, Jaspal, Welker, James, Koura, Firas, Lesnik, Jozef, Eltishcheva, Vera, Libis, Roman, Kamalov, Gadel, Belenky, Dmitry, Egorova, Liudmila, Khokhlov, Alexander, Yakupov, Eduard, Zateyshchikov, Dmitry, Barbarash, Olga, Miller, Olga, Mazur, Evgeniy, Zrazhevskiy, Konstantin, Novikova, Tatyana, Moiseeva, Yulia, Polkanova, Elena, Sobolev, Konstantin, Rossovskaya, Maria, Shapovalova, Yulia, Kolesnikova, Alla, Nikolaev, Konstantin, Zemlianskaia, Oksana, Zateyshchikova, Anna, Popov, Sergey, Poltayskaya, Maria, Edin, Anton, Aleksandrova, Elena, Drapkina, Oksana, Vishnevsky, Alexander, Nagibovich, Oleg, Chizhov, Petr, Rachkova, Svetlana, Sergeev, Mikhail, Kurylo, Borys, Ushakov, Alexey, Alvarez Garcia, Pere, Lopez Fernandez, Maria Fernanda, Toran Monserrat, Pere, Marquez Contreras, Emilio, Isart Rafecas, Jordi, Motero Carrasco, Juan, Garcia Pavia, Pablo, Gomez Pajuelo, Casimiro, Rincon Diaz, Luis Miguel, Iglesias Alonso, Luis Fernando, Grande Ruiz, Angel, Merce Klein, Jordi, Gonzalez Juanatey, Jose Ramon, Monte Collado, Ines, Palacin Piquero, Herminia, Brotons Cuixart, Carles, Fernandez Escobar, Esther, Bayo i Llibre, Joan, Corros Vicente, Cecilia, Vida Gutierrez, Manuel, Evans, Paul, Clark, M., Bisatt, John, Litchfield, Jennifer, Fisher, E., Fooks, Tim, Kelsall, Richard, Paul, Neil, Alborough, Elizabeth, Aziz, Michael, Ramesh, C., Wilson, Pete, Franklin, Simon, Fairhead, Sue, Thompson, Julian, Chowan, Hasan, Taylor, Gary, Tragen, Dawn, Parfitt, Matt, Seamark, Claire, Richardson, Mark, Jefferies, Angus, Sharp, Helen, Jones, Hywel, Giles, Claire, Bramley, Matthew, Williams, Philip, Aldegather, Jehad, Wetherell, Simon, Lumb, William, Evans, Phil, Scouller, Frances, Macey, Neil, Rogers, Stephen, Stipp, Yvette, West, Richard, Pinney, Philip, Matthews, John, Pandya, Preeti, Gallagher, Andrew, Railton, T., Davies, Emyr, McClure, Jonathan, Jacobs, Marc, Hutton, Claire, Thompson, R., Sinha, Bijoy, Butter, Keith, Barrow, Susan, Little, Helen, Russell, David, Choudhary, Ulka, Haq, Ikram, Ainsworth, Paul, Jones, Claire, Weeks, Phil, Eden, Jane, Gibbons, Lisa, Glencross, Janet, MacLeod, Alison, Poland, K., Mulolland, Conor, Warke, A., Conn, Paul, Burns, D., Smith, R., Kamath, R., Webster, Jonathan, Hodgins, Ian, Vercoe, Stephen, Roome, Paul, Pinnock, Hilary, Patel, Jayesh, Ali, Amar, Hart, Nigel, Davies, Richard, De-Sousa, Nigel, Neden, Catherine, Danielsen, Mark, Sharma, Purnima, Galloway, Sophia, Hawkins, Charlotte, Oliver, Raife, Aylward, Martin, Pattni, Mira, Irvine, Gordon, Ahmad, Shahid, Rothwell, Catherine, Choudhary, Fiaz, Khalaque, Sabrina, Short, Stephanie, Peters, Sharon, Coulson, Warwick, Roberts, Neil, Coates, Steven, Ward, Ben, Jackson, Daniel, Walton, Steve, Shepherd, Diane, Wong, Toh, Boon, Mark, Deacon, Melanie, Cornelius, David, Davies, Sarah, Ben Frankel, Ben Frankel, Choi, Henry, Sumner, Jon, Myhill, Tim, Estifanos, Salah, Geatch, Diane, Wilkinson, Justin, Veale, Richard, Forshaw, Karen, Hirst, Rob, Zaman, Kashif, Liley, Catherine, Wastling, Rebecca, McEleny, Paul, Beattie, Andre, Cooke, Philip, Wong, Mike, Pugsley, Mark, Dooldeniya, Chaminda, Rogers, Greg, Bennett, James, Muvva, Rajesh, Adam, Matthew, Fox, Robin, Thomas, Nicolas, Cartwright, Simon, Reed, Rory, Randfield, Simon, ACourt, Christine, Flynn, Ann, Halpin, Andrew, Dobson, Simon, Lomax, Louise, Nadaph, Minnal, Goram, Jane, Stoddart, Helen, Simmons, Phil, Shewring, John, Bowen-Simpkins, Emma, Rickenbach, Mark, Munro, Iain, Blenkhorn, Adam, Singh, Bhuwanendu, van Gaal, William, Abhayaratna, Walter, Thomson, Philip, Lehman, Ron, Kilian, Jens, Coulshed, David, Camm, A. John, Fitzmaurice, David A., Illingworth, Laura, Kayani, Gloria, Kakkar, Ajay K., YILMAZ, MEHMET BİRHAN, Taga, Kuniaki, Techigawara, Masaaki, Igarashi, Mono, Watanabe, Hiroshi, Seo, Toshihiko, Hiramitsu, Shinya, Hosokawa, Hiroaki, Hoshiai, Mitsumoto, Hibino, Michitaka, Miyagawa, Koichi, Horie, Hideki, Turpie, Alexander G. G., van Eickels, Martin, Hacke, Werner, Mantovani, Lorenzo G., Misselwitz, Frank, Pieper, Karen S., Kayani, Glo-ria, Fox, Keith A. A., Gersh, Bernard J., Lucas Luciardi, Hector, Gibbs, Harry, Brodmann, Marianne, Cools, Frank, Pereira Barrett, Antonio Carlos, Connolly, Stuart J., Spyropoulos, Alex, Eikelboom, John, Corbalan, Ramon, Hu, Dayi, Nielsen, JOrn Dalsgaard, Ragy, Hany, Raatikainen, Pekka, Le Heuzey, Jean-Yves, Darius, Harald, Keltai, Matyas, Kakkar, Sanjay, Sawhney, Jitendra Pal Singh, Agnelli, Giancarlo, Koretsune, Yukihiro, Sanchez Diaz, Carlos Jerjes, Ten Cate, Hugo, Panchenko, Elizaveta, Lim, Toon Wei, Jacobson, Barry, Oh, Seil, Vinolas, Xavier, Rosenqvist, Marten, Steffel, Jan, Angchaisuksiri, Pantep, Oto, Ali, Parkhomenko, Alex, Al Mahmeed, Wael, Fitzmaurice, David, Chen, Kangning, Zhao, Yusheng, Zhang, Huaiqin, Chen, Jiyan, Cao, Shiping, Wang, Daowen, Yang, Yuejin, Li, Weihua, Li, Hui, Yin, Yuehui, Tao, Guizhou, Kothiwale, Veerappa Annasaheb, Kimura, Teruaki, Raghuraman, Bagirath, Vijan, Vinod Madan, Sawhney, Jitendra, Khan, Aziz, Meena, Ramdhan, Okuda, Fumio, Mizuguchi, Masato, Mukawa, Hiroaki, Chopada, Manojkumar, Abraham, Sunitha, Bisne, Vikas, Vijayaraghavan, Govindan, Roy, Debabrata, Durgaprasad, Rajashekhar, Shankar, A. G. Ravi, Kumar, Sunil, Jain, Dinesh, Bhargava, Kartikeya, Kumar, Vinay, Nagamalesh, Udigala Madappa, Rajput, Rajeeve Kumar, Kanamori, Seishu, Wada, Masamichi, Minagawa, Taro, Ishiguro, Motoyuki, Yamamoto, Kenichi, Kumagai, Koichiro, Katsuda, Yosuke, Yoshida, Keiki, Toyota, Fumitoshi, Mizuno, Yuji, Misumi, Ikuo, Noguchi, Hiroo, Ando, Shinichi, Suetsugu, Tetsuro, Minamoto, Masahiro, Oda, Hiroyuki, Adachi, Susumu, Chiba, Kei, Norita, Hiroaki, Tsuruta, Makoto, Koyanagi, Takeshi, Matsuta, Masahiro, Ito, Kenichiro, Nakano, Masayuki, Shibuya, Mitsuhiro, Stepinska, Janina, Jansky, Petr, Yamamoto, Kunihiko, Haas, Sylvia, Ando, Hiroshi, Higashi, Takayuki, Okada, Megumi, Azakami, Shiro, Komaki, Shinichiro, Kumeda, Kenshi, Murayama, Takashi, Matsumura, Jun, Oba, Yurika, Sonoda, Ryuji, Goto, Kazuo, Minoda, Kotaro, Haraguchi, Yoshikuni, Suefuji, Hisakazu, Miyagi, Hiroo, Kato, Hitoshi, Nakamura, Tsugihiro, Nakamura, Tadashi, Nandate, Hidekazu, Zaitsu, Ryuji, Fujiura, Yoshihisa, Yoshimura, Akira, Numata, Hiroyuki, Ogawa, Jun, Murakami, Kinshiro, Wakasa, Yutaka, Yamasawa, Masanori, Maekawa, Hiromitsu, Abe, Sumihisa, Kihara, Hajime, Tsunoda, Satoru, Saito, Katsumi, Tachibana, Hiroki, Oba, Ichiro, Kuwahata, Takashi, Higa, Satoshi, Gushiken, Masamichi, Eto, Takuma, Chibana, Hidetoshi, Fujisawa, Kazuaki, Shiga, Yuhei, Sumi, Hirokuni, Nagatomo, Toshihisa, Atsuchi, Yoshihiko, Nagoshi, Toshiro, Sanno, Kazuhisa, Hoshino, Fumihiro, Yokota, Naoto, Kameko, Masahiro, Tabuchi, Toshifumi, Ishizawa, Munesumi, Fujiura, Yoshitake, Ikeda, Daisuke, Seto, Taku, Iwao, Tetsu, Ishioka, Norio, Oshiro, Koichi, Tsuchida, Keizo, Hatori, Yutaka, Takeuchi, Motoshi, Takezawa, Hiroto, Kira, Tetsuya, Tada, Masato, Tsuzaki, Ken, Miura, Naoya, Fujisawa, Yasuaki, Furumoto, Wataru, Suzuki, Susumu, Fujisawa, Akinori, Nakamura, Ryosai, Komatsu, Hiroyasu, Fujiki, Rei, Kawano, Shuichi, Nishizawa, Keijiro, Kato, Yoji, Azuma, Junya, Yasui, Kiyoshi, Amano, Toshio, Sekine, Yasuhiro, Honzawa, Tatsuo, Koshibu, Yuichiro, Sakamoto, Yasuhide, Seta, Yukihiro, Miyaguchi, Shingo, Morishita, Kojuro, Samejima, Yasuko, Sasaki, Toyoshi, Iseki, Fumiko, Kobayashi, Toshiyuki, Kano, Hiroshi, Kim, Jaeyoung, Yamaguchi, Hiroshi, Takagi, Yoichi, Pearce, Yoko Onuki, Suzuki, Yasuyuki, Fukui, Takayuki, Nakayama, Toni, Kanai, Hideaki, Kawano, Yoshiyuki, Ino, Tetsuji, Miyoshi, Hironori, Miyamoto, Yasufumi, Shigekiyo, Masahito, Ono, Shimato, Okamoto, Yutaka, Ubukata, Satoshi, Kodera, Kojiro, Oriuchi, Tatsuo, Matsumoto, Naoki, Nagano, Shinjiro, Iwaki, Masaaki, Nakamura, Yuichiro, Miyamoto, Naomasa, Taguchi, Toshifumi, Ashida, Ko, Yoshizawa, Naoto, Agata, Jun, Matsukawa, Seishiro, Arasaki, Osamu, Fukuoka, Shuji, Murakami, Hirofumi, Mishima, Kazuya, Hata, Yoshiki, Sakuma, Ichiro, Obunai, Kotaro, Takamura, Ichiro, Akutsu, Mitsuyuki, Unoki, Toshihide, Go, Yoshinori, Ikemura, Makoto, Morii, Shoji, Marusaki, Shigem, Doi, Hideo, Tanaka, Mitsuru, Kusu-moto, Takaaki, Kakinoki, Shigeo, Ogurusu, Chiga, Murata, Kazuya, Shimoyama, Masaki, Nakatsuka, Masami, Kitami, Yutaka, Nakamura, Yoichi, Oda, Hiroshi, Oyama, Rikimaru, Ageta, Masato, Mita, Teruaki, Nagao, Kazuhiko, Mito, Takafumi, Minami, Junichi, Abe, Mitsunori, Fujii, Masako, Okawa, Makoto, Fujito, Tsuneo, Taniguchi, Toshiya, Ko, Tenei, Kubo, Hiroshi, Imamaki, Mizuho, Akiyama, Masahiro, Ueda, Takashi, Odakura, Hironori, Inagaki, Masahiko, Katsube, Yoshiki, Nakata, Atsuyuki, Tomimoto, Shinobu, Sugishita, Nobuyoshi, Shiga, Yukio, Soma, Akira, Neya, Kazuo, Yoshida, Tetsuro, Akahane, Kunio, Adachi, Sen, Takanaka, Chiei, Matsui, Saori, Kanda, Hirofumi, Kaneko, Masanori, Nagasaka, Shiro, Taguchi, Atsushi, Toru, Shuta, Saito, Kazuyuki, Miyashita, Akiko, Sasaguri, Hiroki, Nariyama, Jin, Hatsuno, Taketo, Iwase, Takash, Sato, Kazuki, Kawai, Kazuya, Kotani, Tomobumi, Tsuji, Tsuyoshi, Sakai, Hirosumi, Nishino, Kiyoshi, Ikeda, Kenichi, Maeda, Kazuo, Shinozuka, Tomohiro, Inoue, Takeshi, Kawakami, Koichi, Kitazumi, Hiromichi, Takagi, Tsutomu, Hamaoka, Mamoru, Kojima, Jisho, Sasaki, Akitoshi, Tsuchiya, Yoshihiro, Bet-suyaku, Tetsuo, Higuchi, Koji, Honda, Masaaki, Hasegawa, Koichi, Baba, Takao, Mineoi, Kazuaki, Koeda, Toshihiko, Hirasawa, Kunihiko, Kumazaki, Toshihide, Nakagomi, Akira, Otaki, Eiji, Shindo, Takashi, Hirayama, Hiroyoshi, Sugimoto, Chikako, Yamagishi, Takashi, Mizuguchi, Ichiro, Sezaki, Kazunori, Niwa, Isamu, Takenaka, Ken, Iiji, Osamu, Taya, Koichi, Kitazawa, Hitoshi, Ueda, Samu, Kakuda, Hirokazu, Ono, Takuya, Oriso, Seizo, Kamata, Junya, Nanke, Toshihiko, Maeda, Itaru, Matsuura, Yoshifusa, Teragawa, Hiroki, Maruyama, Yasuyuki, Takei, Kazuo, Hone, Hajime, Kito, Tetsu-taro, Asano, Hiroshi, Matsushita, Koji, Nakamura, Masaichi, Washizuka, Takashi, Yoshida, Tomoki, Sawano, Masato, Arima, Shinichi, Arai, Hidekazu, Shinohara, Hisanori, Takai, Hiroyuki, Furukawa, Nobufusa, Ota, Akira, Yamamoto, Kentaro, Aoki, Kenji, Yamamoto, Taku, Kasai, Takeaki, Suzuki, Shunji, Suzuki, Shu, Shibata, Nitaro, Watanabe, Masayuki, Nishihata, Yosuke, Arino, Torn, Okuyama, Masaki, Wakiyama, Tetsushi, Kato, Tomoko, Sasagawa, Yasuo, Tana, Takeshi, Tumelero, Rogerio Tadeu, Maia, Lilia, de Almeida, Roberto Simoes, Carmo Borges, Ney Carter, Gomes Ferreira, Luis Gustavo, Stockins Fernandez, Benjamin Aleck Joseh, Montecinos, Humberto, Lanas, Fernando, Larico Gomez, Martin, Astudillo, Carlos, Conejeros, Carlos, Marin Cuevas, Patricio, Forero, Alejandro, Bugueno Gutierrez, Claudio, Aguilar, Juan, Potthoff Cardenas, Sergio, Eggers, German, Houzvic, Cesar, Rey, Carlos, Arriagada, German, Charme Vilches, Gustavo, Illescas Diaz, Jesus Jaime, Leal Cantu, Raul, Ramos Zavala, Maria Guadalupe, Cabrera Jardines, Ricardo, Espinola Zavaleta, Nilda, Lopez Rosas, Enrique, Llamas Esperon, Guillermo Antonio, Pozas, Gerardo, Cardona Munoz, Ernesto, Her-nandez, Norberto Matadamas, Leyva Rendon, Adolfo, Garcia Hernandez, Norberto, de los Rios Ibarra, Manuel, Virgen Carrillo, Luis Ramon, Lopez Villezca, David, Hernandez Herrera, Carlos, Lopez Prieto, Juan Jose, Gaona Rodriguez, Rodolfo, Villeda Espinosa, Efrain, Flores Martinez, David, Velasco Barcena, Jose, Fierro Fierro, Omar, Rodriguez Briones, Ignacio, Leiva Pons, Jose Luis, Alvarez Lopez, Humberto, Olvera Ruiz, Rafael, Cantu Brito, Carlos Gerardo, Chuquiure Valenzuela, Eduardo Julian Jose Roberto, Reyes Sanchez, Roxana, Bazzoni Ruiz, Alberto Esteban, Lopez Ruiz, Oscar Martin, Arriaga Nava, Roberto, Morales Cerda, Jesus David, Fajardo Campos, Pedro, Benavides Gonzalez, Mario, Lenz, Kurt, Hagn, Claus, Foechterle, Johannes, Drexel, Heinz, Huber, Kurt, Podczeck-Schweighofer, Andrea, Winkler, Michael, Schneeweiss, Bruno, Gegenhuber, Alfons, Lang, Wilfried, Eichinger-Hasenauer, Sabine, Kaserer, Peter, Sykora, Josef, Rasch, Heribert, Strohmer, Bernhard, Capiau, Luc, Vervoort, Geert, Wollaert, Bart, Hollanders, Geert, Vercammen, Jan, Balthazar, Yohan, Delforge, Marc, Xhaet, Olivier, Striekwold, Harry, Thoeng, John, Hermans, Kurt, Mairesse, Georges, Anne, Wim, Blankoff, Ivan, Beutels, Michel, Vandergoten, Peter, Purnode, Philippe, Godart, Pascal, Boussy, Tim, Desfontaines, Philippe, Heyse, Alex, Voet, Joeri, De Wolf, Axel, Zidkova, Eva, Spacek, Rudolf, Machova, Vilma, Ludka, Ondrej, Olsr, Josef, Kotik, Lubos, Racz, Blazej, Ferkl, Richard, Hubac, Jan, Kotik, Ilja, Monhart, Zdenek, Burianova, Hana, Jerabek, Ondrej, Pisova, Jana, Petrova, Iveta, Dedek, Vratislav, Honkova, Michaela, Podrazil, Petr, Reichert, Petr, Spinar, Jindrich, Novak, Miroslav, Durdil, Vaclav, Plocova, Katarina, Lastuvka, Jiri, Nielsen, Jorn, Hayashi, Yoshihito, Hirota, Shinichi, Abe, Yukihiko, Saito, Yoshihiro, Uchiyama, Hirohide, Takeda, Hiroshi, Ono, Hiroshi, Tohyo, Shuichi, Hanazono, Naoto, Miyajima, Seiichi, Shimono, Hisashi, Aoyama, Takuma, Shozawa, Yasunobu, Niijima, Yawara, Murai, Osamu, Inaba, Hideko, Nomura, Katsumasa, Nozoe, Masatsugu, Suzuki, Kazuo, Furukawa, Toshiyuki, Shiraiwa, Toshihiko, Ito, Nobuhisa, Nagai, Shunichi, Sato, Kiyoharu, Nakahara, Shiro, Shimoyama, Yujin, Ohara, Naoko, Kozuka, Teruhiko, Okita, Hideaki, Endo, Masato, Goto, Tsutomu, Hirose, Makoto, Nagata, Emiko, Nakanishi, Noriyuki, Mori, Toshizumi, Seki, Shuichi, Okamoto, Katsuhiro, Moriai, Osamu, Emura, Yoko, Fukuda, Tsuyoshi, Date, Haruhiko, Kawakami, Shuichi, Nagai, Sho, Ueyama, Yuya, Fudo, Tetsuro, Imaizumi, Mitsuru, Ogawa, Takuo, Take, Shunsuke, Ikeda, Hideo, Nishioka, Hiroaki, Sakamoto, Norihiko, Ikeoka, Kiyomitsu, Wakaki, Nobuo, Abe, Masatake, Doiuchi, Junji, Inagaki, Koichi, Iseki, Atsushi, Yoshida, Tomohiro, Goda, Toshihiro, Katsuki, Tsukasa, Sato, Atsushi, Mori, Etsuo, Tsubokura, Toshio, Shudo, Hiroshi, Fujimoto, Shunichi, Katsuya, Tomohiro, Furukawa, Yoshiyuki, Hosokawa, Hiroshi, Narumi, Jun, Yamamoto, Kiichiro, Owari, Masaki, Inakura, Takuya, Anno, Takafumi, Shirakawa, Kazuyuki, Ching, Chi Keong, Foo, David, Wong, Kelvin, Yuyang, Tan, Park, Hui Nam, Kim, Woo-Shik, Lee, HyeYoung, Jang, Sung-Won, Kim, Dae Hyeok, Kim, Jun, Ryu, DongRyeol, Shim, Jaemin, Kim, Dae-Kyeong, Choi, Dong Ju, Oh, Yong Seog, Cho, Myeong-Chan, Kim, Hack-Lyoung, Jeon, Hui-Kyung, Shin, Dong-Gu, Park, Sang Weon, Park, Hoon Ki, Han, Sang-Jin, Sung, Jung Hoon, Park, Hyung-Wook, Nam, Gi-Byoung, On, Young Keun, Lim, Hong Euy, Kwak, JaeJin, Cha, Tae-Joon, Hong, Taek Jong, Park, Seong Hoon, Yoon, Jung Han, Kim, Nam-Ho, Kim, Kee-Sik, Jung, Byung Chun, Hwang, Gyo-Seung, Kim, Chong-Jin, Rungaramsin, Sakda, Katekangplu, Peerapat, Khunrong, Porames, Bunyapipat, Thanita, Wongcharoen, Wanwarang, Kaewsuwanna, Pinij, Siriwattana, Khanchai, Tiyanon, Waraporn, Pattanaprichakul, Supalerk, Likittanasombat, Khanchit, Cholsaringkarl, Doungrat, Boonyapisit, Warangkana, Cheewatanakornkul, Sirichai, Silaruks, Songkwan, Hutayanon, Pisit, Chawanadelert, Seksan, Chattranukulchai, Pairoj, Chatlaong, Boonsert, Santanakorn, Yingsak, Kanokphatcharakun, Khompiya, Mongkolwongroj, Piya, Jai-Aue, Sasivimon, Komson, Ongkarn, Altun, Armagan, Aydinlar, Ali, Ongen, Zeki, Acikel, Sadik, Sahin, Durmus Yildiray, Yilmaz, Ozcan, Pekdemir, Hasan, Demir, Mesut, Sucu, Murat, Sahiner, Levent, Ersanli, Murat, Okuyan, Ertugrul, Aras, Dursun, Rolandi, Florencia, Cesar Ingaramo, Adrian, Alberto Sambadaro, Gustavo, Fernandez Caputi, Vanina, Luciardi, Hector, Graciela Berman, Sofia, Dragotto, Pablo, Poli, Daniela, Quintavalla, Roberto, Cosmi, Franco, Fanelli, Raffaele, Oriana, Vincenzo, Reggio, Raffaele, Anti, Roberto S., Pancaldi, Leonardo, De Cristofaro, Raimondo, Guazzaloca, Giuliana, De Blasio, Angelo, Uriate, Jorge Salerno, Lillo, Flavia, Pogliani, Enrico Maria, Javier Kleiban, Andres, Ahuad Guerrero, Rodolfo Andres, Adalberto Di Paola, Leonel, Dario Dran, Ricardo, Egido, Javier, Jose Fosco, Matias, Rodolfo Cartasegna, Luis, Gomez Vilamajo, Oscar, Luis Ramos, Jose, Sassone, Sonia, Zapata, Gerardo, Conde, Diego, Giacomi, Guillermo, Alfredo Fernandez, Alberto, Alberto Berli, Mario, Ferroni, Fabian, Sobral Filho, Dario Celestino, Jaber, Jefferson, Armaganijan, Luciana Vidal, Frack Costantini, Costantino Roberto, Steffens, Andre, Sebba Barroso de Souzaem, Weimar Kunz, de Souza Neto, Joao David, Ribeiro, Jose Marcio, Teixeira, Marcelo Silveira, Rossi, Paulo, Pires, Leonardo, Moreira, Daniel, Moura Jorge, Jose Carlos, Lorga Filho, Adalberto Menezes, Bodanese, Luiz, Montera, Marcelo Westerlund, Del Carlo, Carlos Henrique, Saad, Jamil Abdalla, Alves Costa, Fernando Augusto, Lopes, Renato, de Aranjo, Gilson Roberto, Manenti, Euler Roberto, Kerr Saraiva, Jose Francisco, Ferreira Braga, Joao Carlos, Negri, Alexandre, Moncada, Carlos, Precoma, Dalton, Roquette, Fernando, Reis, Gilmar, Ramos Filho, Roberto Alvaro, Figueiredo, Estevao Lanna, Botelho, Roberto Vieira, Fontoura Tavares, Claudio Munhoz, Finimundi, Helius Carlos, Kochi, Adriano, Broilo Franca, Cesar Cassio, Alban, Fabio, Aranha Rosito, Guido Bernardo, de Moura Xavier Moraes Junior, Joao Batista, Husted, Steen, Hintze, Ulrik, Rasmussen, Soren, Sygehus, Nwstved, Bremmelgaard, Arne, Markenvard, John, Borger, Jan, Solgaard, Jorgen, Eriksen, Ebbe, Lokkegaard, Thomas, Bruun, Michael, Mertz, Jacob, Schou, Morten, Olsen, Michael, Viitanen, Carmela, Paganelli, Franck, Ohayon, Joel, Casassus, Frederic, Galinier, Michel, Gottwalles, Yannick, Loiselet, Philippe, Koujan, Mohamed Bassel, Destrac, Sylvain, Piot, Olivier, Cebron, Jean-Pierre, Guenoun, Maxime, Guedj-Meynier, Dominique, Lokesh, A. G., Zuber, Mathieu, Amarenco, Pierre, Ellie, Emmanuel, Kadouch, James, Huberman, Jean-Pierre, Lemaire, Nestor, Rodier, Gilles, Vandamme, Xavier, Sibon, Igor, Neau, Jean-Philippe, Mahagne, Marie Helene, Mielot, Antoine, Bonnefoy, Marc, Churet, Jean-Baptiste, Navarre, Vincent, Sellem, Frederic, Monniot, Gilles, Boyes, Jean-Paul, Doucet, Bernard, Martelet, Michel, Obadia, Desire, Crousillat, Bernard, Mouallem, Joseph, Bearez, Etienne, Brugnaux, Jean Philippe, Fedorowsky, Alain, Nazeyrollas, Pierre, Berneau, Jean-Baptiste, Chemin, Frederic, Schellong, Sebastien, Koeniger, Georg, Kopf, Andreas, Gerbaulet, Uwe, Kellner, Bernd-Thomas, Schaefer, Thomas, Purr, Jan, Eissfeller, Enno, Zauzig, Heinz-Dieter, Riegel, Peter, Axthelm, Christoph, Heinz, Gerd-Ulrich, Pustelnik, Andreas, Zutz, Stefan, Eder, Wolfgang, Rehling, Guenter, Glatzel, Dirk, Ludwig, Norbert, Sandow, Petra, Wiswedel, Henning, Wildenauer, Cosmas, Schoen, Steffen, Schwarz, Toralf, Babyesiza, Adyeri, Kropp, Maximilian, Zimny, Hans-Hermann, Kahl, Friedhelm, Caspar, Andreas, Omankowsky, Sabine, Laessig, Torsten, Hartmann, Hermann-Josef, Lehmann, Gunter, Bindig, Hans-Walter, Hergdt, Gunter, Reimer, Dietrich, Hauk, Joachim, Michel, Holger, Dres, Praxis, Erdle, Werner, Dorsch, Wilfried, Dshabrailov, Janna, Rapp, Karl-Albrecht, Epelde Gonzalo, Francisco, Almeida Fernandez, Carlos Alexandre, Martinez Navarro, Encarnacion, Montero Alia, Juan Jose, Barreda Gonzalez, Maria, Moleiro Oliva, Maria Angels, Iglesias Sanmartin, Jose, Rodriguez Alvarez, Maria del Mar, Ripoll Vera, Tomas, Jimenez Navarro, Manuel, Vazquez Caamano, Maria, Arcocha Tones, Maria Fe, Marcos Gomez, Gonzalo, Iniguez Romo, Andres, Prieto Diaz, Miguel Angel, Wirdby, Alexander, Linden, Jan, and Henriksson, Kerstin

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Hemorrhage, 030204 cardiovascular system & hematology, antiplatelet therapy, Coronary artery disease, Anticoagulation, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Cause of Death, Internal medicine, Atrial Fibrillation, medicine, Humans, 030212 general & internal medicine, Acute Coronary Syndrome, bleeding, mortality, stroke, Stroke, Aged, Proportional Hazards Models, business.industry, Hazard ratio, Anticoagulants, Atrial fibrillation, General Medicine, Prognosis, medicine.disease, Blood pressure, Cardiovascular Diseases, Heart failure, Cardiology, Female, Liver function, business, Platelet Aggregation Inhibitors, Follow-Up Studies
Abstract

Item does not contain fulltext BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes. METHODS: Adults with newly diagnosed atrial fibrillation and >/=1 investigator-defined stroke risk factor were enrolled in GARFIELD-AF between March 2010 and September 2015. The association between prior acute coronary syndromes and long-term outcomes was determined using a Cox proportional hazards model, adjusting for baseline risk factors, oral anticoagulation (OAC) +/- antiplatelet (AP) therapy, and usual care. RESULTS: Of 39,679 patients, 10.5% had a history of acute coronary syndromes. At 2-year follow-up, patients with prior acute coronary syndromes had higher adjusted risks of stroke/systemic embolism (hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.08-1.78), major bleeding (HR 1.30; 95% CI, 0.95 -1.79), all-cause mortality (HR 1.34; 95% CI, 1.21 -1.49), cardiovascular mortality (HR 1.85; 95% CI, 1.51-2.26), and new acute coronary syndromes (HR 3.42; 95% CI, 2.62-4.45). Comparing antithrombotic therapy in the acute coronary syndromes vs no acute coronary syndromes groups, most patients received OAC +/- AP: 60.8% vs 66.1%, but AP therapy was more likely in the acute coronary syndromes group (68.1% vs 32.9%), either alone (34.9% vs 20.8%) or with OAC (33.2% vs 12.1%). Overall, 17.8% in the acute coronary syndromes group received dual AP therapy with (5.3%) or without OAC (12.5%). Among patients with moderate/high risk for stroke/systemic embolism, fewer in the acute coronary syndromes group received OAC with or without AP therapy (Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category [CHA2DS2-VASc] 2: 52.1% vs 64.6%; CHA2DS2-VASc >/=3: 62.0% vs 70.7%), and the majority with a Hypertension (uncontrolled systolic blood pressure >160 mm Hg), Abnormal renal or liver function, previous Stroke, Bleeding history or predisposition, Labile international normalized ratios, Elderly, and concomitant Drugs or alcohol excess (HAS-BLED) score >/=3 were on AP therapy (83.8% vs 65.5%). CONCLUSIONS: In GARFIELD-AF, previous acute coronary syndromes are associated with worse 2-year outcomes and a greater likelihood of under-treatment with OAC, while two-thirds of patients receive AP therapy. Major bleeding was more common with previous acute coronary syndromes, even after adjusting for all risk factors.

Published
2019
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10. Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Author

Maggioni, Aldo P., Greene, Stephen J., Fonarow, Gregg C., Böhm, Michael, Zannad, Faiez, Solomon, Scott D., Lewis, Eldrin F., Baschiera, Fabio, Hua, Tsushung A., Gimpelewicz, Claudio R., Lesogor, Anastasia, Gheorghiade, Mihai, Ramos, Silvina, Luna, Alejandra, Miriuka, Santiago, Diez, Mirta, Perna, Eduardo, Luquez, Hugo, Pinna, Jorge Garcia, Castagnino, Jorge, Alvarenga, Pablo, Ibañez, Julio, Blumberg, Eduardo Salmon, Dizeo, Claudio, Guerrero, Rodolfo Ahuad, Schygiel, Pablo, Milesi, Rodolfo, Sosa, Carlos, Hominal, Miguel, Marquez, Lilia Lobo, Poy, Carlos, Hasbani, Eduardo, Vico, Marisa, Fernandez, Alberto, Vita, Nestor, Vanhaecke, Johan, De Keulenaer, Gilles, Striekwold, Harry, Vervoort, Geert, Vrolix, Mathias, Henry, Philippe, Dendale, Paul, Smolders, Walter, Marechal, Patrick, Vandekerckhove, Hans, Oliveira, Mucio, Neuenschwande, Fernando, Reis, Gilmar, Saraiva, Jose, Bodanese, Luiz, Canesin, Manoel, Greco, Oswaldo, Bassan, Roberto, Marino, Roberto Luis, Giannetti, Nadia, Moe, Gordon, Sussex, Bruce, Sheppard, Richard, Huynh, Thao, Stewart, Robert, Haddad, Haissam, Echeverria, Luis, Quintero, Adalberto, Torres, Adriana, Jaramillo, Mónica, Lopez, Mónica, Mendoza, Fernan, Florez, Noel, Cotes, Carlos, Garcia, Magali, Belohlavek, Jan, Hradec, Jaromir, Peterka, Martin, Gregor, Pavel, Monhart, Zdenek, Jansky, Petr, Kettner, Jiri, Reichert, Petr, Spinar, Jindrich, Brabec, Tomas, Hutyra, Martin, Solar, Miroslav, Pietilä, Mikko, Nyman, Kai, Pajari, Risto, Cohen, Ariel, Galinier, Michel, Gosse, Philippe, Livarek, Bernard, Neuder, Yannick, Jourdain, Patrick, Picard, François, Isnard, Richard, Hoppe, Uta, Kaeaeb, Stefan, Rosocha, Stefan, Prondzinsky, Roland, Felix, Stephan, Duengen, Hans-Dirk, Figulla, Hans-Reiner, Fischer, Sven, Behrens, Steffen, Stawowy, Philipp, Kruells-Muench, Juergen, Knebel, Fabian, Nienaber, Christoph, Werner, Dierk, Aron, Wilma, Remppis, Bjoern, Hambrecht, Rainer, Kisters, Klaus, Werner, Nikos, Hoffmann, Stefan, Rossol, Siegbert, Geiss, Ernst, Graf, Kristof, Hamann, Frank, von Scheidt, Wolfgang, Schwinger, Robert, Tebbe, Ulrich, Costard-Jaeckle, Angelika, Lueders, Stephan, Heitzer, Thomas, Leutermann-Oei, Marie-Louise, Braun-Dullaeus, Ruediger, Roehnisch, Jens-Uwe, Muth, Gerhard, Goette, Andreas, Rotter, Achim, Ebelt, Henning, Olbrich, Hans-Georg, Mitrovic, Veselin, Hengstenberg, Christian, Schellong, Sebastian, Zamolyi, Karoly, Vertes, Andras, Matoltsy, Andras, Palinkas, Attila, Herczeg, Bela, Apro, Dezso, Lupkovics, Geza, Tomcsanyi, Janos, Toth, Kalman, Mathur, Atul, Banker, Darshan, Bharani, Anil, Arneja, Jaspal, Khan, Aziz, Gadkari, Milind, Hiremath, Jagdish, Patki, Nitin, Kumbla, Makund, Santosh, M.J., Ravikishore, A.G., Abhaichand, Rajpal, Maniyal, Vijayakukmar, Nanjappa, Manjunath, Reddy, P. Naveen, Chockalingam, Kulasekaran, Premchand, Rajendra, Mahajan, Vijay, Lewis, Basil, Wexler, Dov, Shochat, Michael, Keren, Andre, Omary, Muhamad, Katz, Amos, Marmor, Alon, Lembo, Giuseppe, Di Somma, Salvatore, Boccanelli, Alessandro, Barbiero, Mario, Pajes, Giuseppe, De Servi, Stefano, Greco, Dott Cosimo, De Santis, Fernando, Floresta, Agata, Visconti, Luigi Oltrona, Piovaccari, Giancarlo, Cavallini, Claudio, Di Biase, Matteo, Masini, Dott Franco, Vassanelli, Corrado, Viecca, Maurizio, Cangemi, Dott Francesco, Pirelli, Salvatore, Borghi, Claudio, Volpe, Massimo, Branzi, Angelo, Percoco, Dott Giovanni, Severi, Silvia, Santini, Alberto, De Lorenzi, Ettore, Metra, Marco, Zacà, Valerio, Mortara, Andrea, Tranquilino, Francisco P., Babilonia, Noe A., Ferrolino, Arthur M., Manlutac, Benjamin, Dluzniewski, Miroslaw, Dzielinska, Zofia, Nowalany-Kozie, Ewa, Mazurek, Walentyna, Wierzchowiecki, Jerzy, Wysokinski, Andrzej, Szachniewicz, Joanna, Romanowski, Witold, Krauze-Wielicka, Magdalena, Jankowski, Piotr, Berkowski, Piotr, Szelemej, Roman, Kleinrok, Andrzej, Kornacewicz-Jac, Zdzislawa, Vintila, Marius, Vladoianu, Mircea, Militaru, Constantin, Dan, Gheorghe, Dorobantu, Maria, Dragulescu, Stefan, Kostenko, Victor, Vishnevsky, Alexandr, Goloschekin, Boris, Tyrenko, Vadim, Gordienko, Alexander, Kislyak, Oxana, Martsevich, Sergey, Kuchmin, Alexey, Karpov, Yurii, Fomin, Igor, Shvarts, Yury, Orlikova, Olga, Ershova, Olga, Berkovich, Olga, Sitnikova, Maria, Pakhomova, Inna, Boldueva, Svetlana, Tyurina, Tatiana, Simanenkov, Vladimir, Boyarkin, Mikhail, Novikova, Nina, Tereschenko, Sergey, Zadionchenko, Vladimir, Shogenov, Zaur, Gordeev, Ivan, Moiseev, Valentin, Wong, Raymond, Ong, Hean Yee, Le Tan, Ju, Goncalvesova, Eva, Kovar, Frantisek, Skalina, Ivan, Kasperova, Viera, Hojerova, Silvia, Szentivanyi, Miroslav, Stancak, Branislav, Babcak, Marian, Kycina, Peter, Poliacik, Pavol, Toth, Peter, Sirotiakova, Jana, de Sa, Esteban Lopez, Bueno, Manuel Gomez, Selles, Manuel Martinez, Cabrera, Jose Angel, Freire, Ramon Bover, Gonzalez Juanatey, Jose Ramon, Comin, Josep, Soriano, FranciscoRidocci, Lopez, Alejandro, Vicho, Raul, Lama, Manuel Geraldia, Schaufelberger, Maria, Brunotte, Richard, Ullman, Bengt, Hagerman, Inger, Cizinsky, Stella, Cherng, Wen-Jin, Yu, Wen-Chung, Kuo, Chi-Tai, Chang, Kuan-Cheng, Lai, Wen-Ter, Kuo, Jen-Yuan, Ural, Dilek, Badak, Ozer, Akin, Mustafa, Yigit, Zerrin, Yokusoglu, Mehmet, Yilmaz, Mehmet, Abaci, Adnan, Ebinc, Haksun, Perlman, Richard, Parish, David, Bergin, James, Burnham, Kenneth, Brown, Christopher, Lundbye, Justin, Williams, Celeste, Eisen, Howard, Juneman, Elizabeth, Joseph, Susan, Peberdy, Mary Ann, Peura, Jennifer, Gupta, Vishal, Habet, Kalim, French, William, Mody, Freny, Graham, Susan, Hazelrigg, Monica, Chung, Eugene, Dunlap, Stephanie, Nikolaidis, Lazaros, Najjar, Samer, Katz, Richard, Murali, Srinivas, Izzo, Joseph L., Callister, Tracy, Phillips, Roland, Lippolis, Nicholas, Winterton, John, Meymandi, Sheba, Heilman, Karl, Oren, Ron, Zolty, Ronald, Brottman, Michael, Gunawardena, D.R., Adams, Kirkwood, Barnard, Denise, Klapholz, Marc, Fulmer, James, Maggioni AP, Greene SJ, Fonarow GC, Böhm M, Zannad F, Solomon SD, Lewis EF, Baschiera F, Hua TA, Gimpelewicz CR, Lesogor A, Gheorghiade M, Ramos S, Luna A, Miriuka S, Diez M, Perna E, Luquez H, Pinna JG, Castagnino J, Alvarenga P, Ibañez J, Blumberg ES, Dizeo C, Guerrero RA, Schygiel P, Milesi R, Sosa C, Hominal M, Marquez LL, Poy C, Hasbani E, Vico M, Fernandez A, Vita N, Vanhaecke J, De Keulenaer G, Striekwold H, Vervoort G, Vrolix M, Henry P, Dendale P, Smolders W, Marechal P, Vandekerckhove H, Oliveira M, Neuenschwande F, Reis G, Saraiva J, Bodanese L, Canesin M, Greco O, Bassan R, Marino RL, Giannetti N, Moe G, Sussex B, Sheppard R, Huynh T, Stewart R, Haddad H, Echeverria L, Quintero A, Torres A, Jaramillo M, Lopez M, Mendoza F, Florez N, Cotes C, Garcia M, Belohlavek J, Hradec J, Peterka M, Gregor P, Monhart Z, Jansky P, Kettner J, Reichert P, Spinar J, Brabec T, Hutyra M, Solar M, Pietilä M, Nyman K, Pajari R, Cohen A, Galinier M, Gosse P, Livarek B, Neuder Y, Jourdain P, Picard F, Isnard R, Hoppe U, Kaeaeb S, Rosocha S, Prondzinsky R, Felix S, Duengen HD, Figulla HR, Fischer S, Behrens S, Stawowy P, Kruells-Muench J, Knebel F, Nienaber C, Werner D, Aron W, Remppis B, Hambrecht R, Kisters K, Werner N, Hoffmann S, Rossol S, Geiss E, Graf K, Hamann F, von Scheidt W, Schwinger R, Tebbe U, Costard-Jaeckle A, Lueders S, Heitzer T, Leutermann-Oei ML, Braun-Dullaeus R, Roehnisch JU, Muth G, Goette A, Rotter A, Ebelt H, Olbrich HG, Mitrovic V, Hengstenberg C, Schellong S, Zamolyi K, Vertes A, Matoltsy A, Palinkas A, Herczeg B, Apro D, Lupkovics G, Tomcsanyi J, Toth K, Mathur A, Banker D, Bharani A, Arneja J, Khan A, Gadkari M, Hiremath J, Patki N, Kumbla M, Santosh MJ, Ravikishore AG, Abhaichand R, Maniyal V, Nanjappa M, Reddy PN, Chockalingam K, Premchand R, Mahajan V, Lewis B, Wexler D, Shochat M, Keren A, Omary M, Katz A, Marmor A, Lembo G, Di Somma S, Boccanelli A, Barbiero M, Pajes G, De Servi S, Greco DC, De Santis F, Floresta A, Visconti LO, Piovaccari G, Cavallini C, Di Biase M, Masini DF, Vassanelli C, Viecca M, Cangemi DF, Pirelli S, Borghi C, Volpe M, Branzi A, Percoco DG, Severi S, Santini A, De Lorenzi E, Metra M, Zacà V, Mortara A, Tranquilino FP, Babilonia NA, Ferrolino AM, Manlutac B, Dluzniewski M, Dzielinska Z, Nowalany-Kozie E, Mazurek W, Wierzchowiecki J, Wysokinski A, Szachniewicz J, Romanowski W, Krauze-Wielicka M, Jankowski P, Berkowski P, Szelemej R, Kleinrok A, Kornacewicz-Jac Z, Vintila M, Vladoianu M, Militaru C, Dan G, Dorobantu M, Dragulescu S, Kostenko V, Vishnevsky A, Goloschekin B, Tyrenko V, Gordienko A, Kislyak O, Martsevich S, Kuchmin A, Karpov Y, Fomin I, Shvarts Y, Orlikova O, Ershova O, Berkovich O, Sitnikova M, Pakhomova I, Boldueva S, Tyurina T, Simanenkov V, Boyarkin M, Novikova N, Tereschenko S, Zadionchenko V, Shogenov Z, Gordeev I, Moiseev V, Wong R, Ong HY, Le Tan J, Goncalvesova E, Kovar F, Skalina I, Kasperova V, Hojerova S, Szentivanyi M, Stancak B, Babcak M, Kycina P, Poliacik P, Toth P, Sirotiakova J, Lopez de Sa E, Bueno MG, Selles MM, Cabrera JA, Freire RB, Gonzalez Juanatey JR, Comin J, Soriano F, Lopez A, Vicho R, Lama MG, Schaufelberger M, Brunotte R, Ullman B, Hagerman I, Cizinsky S, Cherng WJ, Yu WC, Kuo CT, Chang KC, Lai WT, Kuo JY, Ural D, Badak O, Akin M, Yigit Z, Yokusoglu M, Yilmaz M, Abaci A, Ebinc H, Perlman R, Parish D, Bergin J, Burnham K, Brown C, Lundbye J, Williams C, Eisen H, Juneman E, Joseph S, Peberdy MA, Peura J, Gupta V, Habet K, French W, Mody F, Graham S, Hazelrigg M, Chung E, Dunlap S, Nikolaidis L, Najjar S, Katz R, Murali S, Izzo JL, Callister T, Phillips R, Lippolis N, Winterton J, Meymandi S, Heilman K, Oren R, Zolty R, Brottman M, Gunawardena DR, Adams K, Barnard D, Klapholz M, and Fulmer J

Subjects
Male, medicine.medical_specialty, Cardiotonic Agents, ASTRONAUT, Diabetic Cardiomyopathies, Administration, Oral, Kaplan-Meier Estimate, Placebo, Diabete, chemistry.chemical_compound, Double-Blind Method, Fumarates, Internal medicine, Diabetes mellitus, Troponin I, Renin, Clinical endpoint, medicine, Humans, Prospective Studies, Heart Failure, Ejection fraction, business.industry, Surrogate endpoint, Aliskiren, Middle Aged, medicine.disease, Amides, Hospitalization, Endocrinology, Death, Sudden, Cardiac, Treatment Outcome, chemistry, Heart failure, Female, Cardiology and Cardiovascular Medicine, business, aliskiren
Abstract

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether alis- kiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post- discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B- type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P ¼ 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P ¼ 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P , 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldoster- one relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P ¼ 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM.

Published
2013

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