47 results on '"Schwende, H"'
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2. Early Initiation of Sacubitril/Valsartan in Patients With Acute Heart Failure and Renal Dysfunction: An Analysis of the TRANSITION Study
- Author
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STRABURZYNSKA-MIGAJ, EWA, primary, SENNI, M., additional, WACHTER, R., additional, FONSECA, C., additional, WITTE, K.K., additional, MUELLER, C., additional, LONN, E., additional, BUTYLIN, D., additional, NOE, A., additional, SCHWENDE, H., additional, LAWRENCE, D., additional, SURYAWANSHI, B., additional, and PASCUAL-FIGAL, D., additional
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- 2023
- Full Text
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3. Comparative effectiveness of sacubitril/valsartan versus angiotensin converting enzyme inhibitors/angiotensin receptor blockers in de novo heart failure patients
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Taha, I, primary, Gomme, J, additional, Suminska, S, additional, Schwende, H, additional, Butylin, D, additional, Doherty, J, additional, Beckmeyer-Borowko, A, additional, and Farries, G, additional
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- 2022
- Full Text
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4. NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study
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Pascual-Figal, D, Wachter, R, Senni, M, Bao, W, Noe, A, Schwende, H, Butylin, D, Prescott, M, Gniot, J, Mozheiko, M, Lelonek, M, Dominguez, A, Horacek, T, Garcia del Rio, E, Kobalava, Z, Mueller, C, Cavusoglu, Y, Straburzynska-Migaj, E, Slanina, M, vom Dahl, J, Ryding, A, Moriarty, A, Robles, M, Villota, J, Quintana, A, Nitschke, T, Garcia Pinilla, J, Bonet, L, Chaaban, S, Filali zaatari, S, Spinar, J, Musial, W, Abdelbaki, K, Belohlavek, J, Fehske, W, Bott, M, Hoegalmen, G, Leiro, M, Ozcan, I, Mullens, W, Kryza, R, Al-Ani, R, Loboz-Grudzien, K, Ermoshkina, L, Hojerova, S, Fernandez, A, Spinarova, L, Lapp, H, Bulut, E, Almeida, F, Vishnevsky, A, Belicova, M, Witte, K, Wong, K, Droogne, W, Delforge, M, Peterka, M, Olbrich, H, Carugo, S, Nessler, J, Mcgill, T, Huegl, B, Akin, I, Moreira, I, Baglikov, A, Thambyrajah, J, Hayes, C, Barrionuevo, M, Yigit, Z, Kaya, H, Klimsa, Z, Radvan, M, Kadel, C, Landmesser, U, Di Tano, G, Lisik, M, Fonseca, C, Oliveira, L, Marques, I, Santos, L, Lenner, E, Letavay, P, Bueno, M, Mota, P, Wong, A, Bailey, K, Foley, P, Hasbani, E, Virani, S, Massih, T, Al-Saif, S, Taborsky, M, Kaislerova, M, Motovska, Z, Cohen, A, Logeart, D, Endemann, D, Ferreira, D, Brito, D, Kycina, P, Bollano, E, Basilio, E, Rubio, L, Aguado, M, Schiavi, L, Zivano, D, Lonn, E, El Sayed, A, Pouleur, A, Heyse, A, Schee, A, Polasek, R, Houra, M, Tribouilloy, C, Seronde, M, Galinier, M, Noutsias, M, Schwimmbeck, P, Voigt, I, Westermann, D, Pulignano, G, Vegsundvaag, J, Da Silva Antunes, J, Monteiro, P, Stevlik, J, Goncalvesova, E, Hulkoova, B, Castro Fernandez, A, Davies, C, Squire, I, Meyer, P, Sheppard, R, Sahin, T, Sochor, K, De Geeter, G, Schmeisser, A, Weil, J, Soares, A, Bulashova, O, Oshurkov, A, Sunderland, S, Glover, J, Exequiel, T, Decoulx, E, Meyer, S, Muenzel, T, Frioes, F, Arbolishvili, G, Tokarcikova, A, Karlstrom, P, Trullas Vila, J, Perez, G, Sankaranarayanan, R, Nageh, T, Alasia, D, Refaat, M, Demirkan, B, Al-Buraiki, J, Karabsheh, S, Pascual-Figal D., Wachter R., Senni M., Bao W., Noe A., Schwende H., Butylin D., Prescott M. F., Gniot J., Mozheiko M., Lelonek M., Dominguez A. R., Horacek T., Garcia del Rio E., Kobalava Z., Mueller C. E., Cavusoglu Y., Straburzynska-Migaj E., Slanina M., vom Dahl J., Ryding A., Moriarty A., Robles M. B., Villota J. N., Quintana A. G., Nitschke T., Garcia Pinilla J. M., Bonet L. A., Chaaban S., Filali zaatari S., Spinar J., Musial W., Abdelbaki K., Belohlavek J., Fehske W., Bott M. C., Hoegalmen G., Leiro M. C., Ozcan I. T., Mullens W., Kryza R., Al-Ani R., Loboz-Grudzien K., Ermoshkina L., Hojerova S., Fernandez A. A., Spinarova L., Lapp H., Bulut E., Almeida F., Vishnevsky A., Belicova M., Witte K., Wong K., Droogne W., Delforge M., Peterka M., Olbrich H. -G., Carugo S., Nessler J., McGill T. H., Huegl B., Akin I., Moreira I., Baglikov A., Thambyrajah J., Hayes C., Barrionuevo M. R., Yigit Z., Kaya H., Klimsa Z., Radvan M., Kadel C., Landmesser U., Di Tano G., Lisik M. B., Fonseca C., Oliveira L., Marques I., Santos L. M., Lenner E., Letavay P., Bueno M. G., Mota P., Wong A., Bailey K., Foley P., Hasbani E., Virani S., Massih T. A., Al-Saif S., Taborsky M., Kaislerova M., Motovska Z., Cohen A. A., Logeart D., Endemann D., Ferreira D., Brito D., Kycina P., Bollano E., Basilio E. G., Rubio L. F., Aguado M. G., Schiavi L. B., Zivano D. F., Lonn E., El Sayed A., Pouleur A. -C., Heyse A., Schee A., Polasek R., Houra M., Tribouilloy C., Seronde M. F., Galinier M., Noutsias M., Schwimmbeck P., Voigt I., Westermann D., Pulignano G., Vegsundvaag J., Da Silva Antunes J. A., Monteiro P., Stevlik J., Goncalvesova E., Hulkoova B., Castro Fernandez A. J., Davies C., Squire I., Meyer P., Sheppard R., Sahin T., Sochor K., De Geeter G., Schmeisser A., Weil J., Soares A. O., Bulashova O. V., Oshurkov A., Sunderland S. J., Glover J., Exequiel T., Decoulx E., Meyer S., Muenzel T., Frioes F., Arbolishvili G., Tokarcikova A., Karlstrom P., Trullas Vila J. C., Perez G. P., Sankaranarayanan R., Nageh T., Alasia D. C., Refaat M., Demirkan B., Al-Buraiki J., Karabsheh S., Pascual-Figal, D, Wachter, R, Senni, M, Bao, W, Noe, A, Schwende, H, Butylin, D, Prescott, M, Gniot, J, Mozheiko, M, Lelonek, M, Dominguez, A, Horacek, T, Garcia del Rio, E, Kobalava, Z, Mueller, C, Cavusoglu, Y, Straburzynska-Migaj, E, Slanina, M, vom Dahl, J, Ryding, A, Moriarty, A, Robles, M, Villota, J, Quintana, A, Nitschke, T, Garcia Pinilla, J, Bonet, L, Chaaban, S, Filali zaatari, S, Spinar, J, Musial, W, Abdelbaki, K, Belohlavek, J, Fehske, W, Bott, M, Hoegalmen, G, Leiro, M, Ozcan, I, Mullens, W, Kryza, R, Al-Ani, R, Loboz-Grudzien, K, Ermoshkina, L, Hojerova, S, Fernandez, A, Spinarova, L, Lapp, H, Bulut, E, Almeida, F, Vishnevsky, A, Belicova, M, Witte, K, Wong, K, Droogne, W, Delforge, M, Peterka, M, Olbrich, H, Carugo, S, Nessler, J, Mcgill, T, Huegl, B, Akin, I, Moreira, I, Baglikov, A, Thambyrajah, J, Hayes, C, Barrionuevo, M, Yigit, Z, Kaya, H, Klimsa, Z, Radvan, M, Kadel, C, Landmesser, U, Di Tano, G, Lisik, M, Fonseca, C, Oliveira, L, Marques, I, Santos, L, Lenner, E, Letavay, P, Bueno, M, Mota, P, Wong, A, Bailey, K, Foley, P, Hasbani, E, Virani, S, Massih, T, Al-Saif, S, Taborsky, M, Kaislerova, M, Motovska, Z, Cohen, A, Logeart, D, Endemann, D, Ferreira, D, Brito, D, Kycina, P, Bollano, E, Basilio, E, Rubio, L, Aguado, M, Schiavi, L, Zivano, D, Lonn, E, El Sayed, A, Pouleur, A, Heyse, A, Schee, A, Polasek, R, Houra, M, Tribouilloy, C, Seronde, M, Galinier, M, Noutsias, M, Schwimmbeck, P, Voigt, I, Westermann, D, Pulignano, G, Vegsundvaag, J, Da Silva Antunes, J, Monteiro, P, Stevlik, J, Goncalvesova, E, Hulkoova, B, Castro Fernandez, A, Davies, C, Squire, I, Meyer, P, Sheppard, R, Sahin, T, Sochor, K, De Geeter, G, Schmeisser, A, Weil, J, Soares, A, Bulashova, O, Oshurkov, A, Sunderland, S, Glover, J, Exequiel, T, Decoulx, E, Meyer, S, Muenzel, T, Frioes, F, Arbolishvili, G, Tokarcikova, A, Karlstrom, P, Trullas Vila, J, Perez, G, Sankaranarayanan, R, Nageh, T, Alasia, D, Refaat, M, Demirkan, B, Al-Buraiki, J, Karabsheh, S, Pascual-Figal D., Wachter R., Senni M., Bao W., Noe A., Schwende H., Butylin D., Prescott M. F., Gniot J., Mozheiko M., Lelonek M., Dominguez A. R., Horacek T., Garcia del Rio E., Kobalava Z., Mueller C. E., Cavusoglu Y., Straburzynska-Migaj E., Slanina M., vom Dahl J., Ryding A., Moriarty A., Robles M. B., Villota J. N., Quintana A. G., Nitschke T., Garcia Pinilla J. M., Bonet L. A., Chaaban S., Filali zaatari S., Spinar J., Musial W., Abdelbaki K., Belohlavek J., Fehske W., Bott M. C., Hoegalmen G., Leiro M. C., Ozcan I. T., Mullens W., Kryza R., Al-Ani R., Loboz-Grudzien K., Ermoshkina L., Hojerova S., Fernandez A. A., Spinarova L., Lapp H., Bulut E., Almeida F., Vishnevsky A., Belicova M., Witte K., Wong K., Droogne W., Delforge M., Peterka M., Olbrich H. -G., Carugo S., Nessler J., McGill T. H., Huegl B., Akin I., Moreira I., Baglikov A., Thambyrajah J., Hayes C., Barrionuevo M. R., Yigit Z., Kaya H., Klimsa Z., Radvan M., Kadel C., Landmesser U., Di Tano G., Lisik M. B., Fonseca C., Oliveira L., Marques I., Santos L. M., Lenner E., Letavay P., Bueno M. G., Mota P., Wong A., Bailey K., Foley P., Hasbani E., Virani S., Massih T. A., Al-Saif S., Taborsky M., Kaislerova M., Motovska Z., Cohen A. A., Logeart D., Endemann D., Ferreira D., Brito D., Kycina P., Bollano E., Basilio E. G., Rubio L. F., Aguado M. G., Schiavi L. B., Zivano D. F., Lonn E., El Sayed A., Pouleur A. -C., Heyse A., Schee A., Polasek R., Houra M., Tribouilloy C., Seronde M. F., Galinier M., Noutsias M., Schwimmbeck P., Voigt I., Westermann D., Pulignano G., Vegsundvaag J., Da Silva Antunes J. A., Monteiro P., Stevlik J., Goncalvesova E., Hulkoova B., Castro Fernandez A. J., Davies C., Squire I., Meyer P., Sheppard R., Sahin T., Sochor K., De Geeter G., Schmeisser A., Weil J., Soares A. O., Bulashova O. V., Oshurkov A., Sunderland S. J., Glover J., Exequiel T., Decoulx E., Meyer S., Muenzel T., Frioes F., Arbolishvili G., Tokarcikova A., Karlstrom P., Trullas Vila J. C., Perez G. P., Sankaranarayanan R., Nageh T., Alasia D. C., Refaat M., Demirkan B., Al-Buraiki J., and Karabsheh S.
- Abstract
Objectives: This study examined the effects of sacubitril/valsartan on N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response. Background: NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF). Methods: Post-hoc analysis of the TRANSITION (Comparison of Pre- and Post-discharge Initiation of Sacubitril/Valsartan Therapy in HFrEF Patients After an Acute Decompensation Event) study, including stabilized ADHF patients with reduced ejection fraction, randomized to open-label sacubitril/valsartan initiation in-hospital (pre-discharge) versus post-discharge. NT-proBNP was measured at randomization (baseline), discharge, and 4 and 10 weeks post-randomization. A favorable NT-proBNP response was defined as reduction to ≤1,000 pg/ml or >30% from baseline. Results: In patients receiving sacubitril/valsartan in-hospital, NT-proBNP was reduced by 28% at discharge, with 46% of patients obtaining favorable NT-proBNP reduction response compared with a 4% reduction and 18% favorable response rate in patients initiated post-discharge (p < 0.001). NT-proBNP was reduced similarly in patients initiating sacubitril/valsartan pre- and post-discharge (reduction at 4 weeks: 25%/22%; 10 weeks: 38%/34%) with comparable favorable response rates (46%/42% and 51%/48% at 4 and 10 weeks, respectively). NT-proBNP favorable response at 4 weeks was associated with lower risk of first heart failure (HF) rehospitalization or cardiovascular death through 26 weeks (hazard ratio: 0.57; 95% confidence interval [CI]: 0.38 to 0.86; p = 0.007). Predictors of a favorable response at 4 weeks were starting dose ≥49/51 mg twice daily, higher baseline NT-proBNP, lower baseline serum creatinine, de novo HF, no atrial fibrillation, angiotensin-converting enzyme inhibitor–naive or angiotensin receptor blocker–naive, and no prior myocardial inf
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- 2020
5. Regulation of Cytosolic Phospholipase A2 in Arachidonic Acid Release of Rat-Liver Macrophages
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Ambs, P., Baccarini, M., Schwende, H., Fitzke, E., Dieter, P., Honn, Kenneth V., editor, Marnett, Lawrence J., editor, Nigam, Santosh, editor, Jones, Robert L., editor, and Wong, Patrick Y.-K., editor
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- 1997
- Full Text
- View/download PDF
6. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study
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Wachter, R, Senni, M, Belohlavek, J, Straburzynska-Migaj, E, Witte, K, Kobalava, Z, Fonseca, C, Goncalvesova, E, Cavusoglu, Y, Fernandez, A, Chaaban, S, Bøhmer, E, Pouleur, A, Mueller, C, Tribouilloy, C, Lonn, E, A L Buraiki, J, Gniot, J, Mozheiko, M, Lelonek, M, Noè, A, Schwende, H, Bao, W, Butylin, D, Pascual-Figal, D, Transition, I, Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z, Fonseca C, Goncalvesova E, Cavusoglu Y, Fernandez A, Chaaban S, Bøhmer E, Pouleur AC, Mueller C, Tribouilloy C, Lonn E, A L Buraiki J, Gniot J, Mozheiko M, Lelonek M, Noè A, Schwende H, Bao W, Butylin D, Pascual-Figal D, TRANSITION Investigators, Wachter, R, Senni, M, Belohlavek, J, Straburzynska-Migaj, E, Witte, K, Kobalava, Z, Fonseca, C, Goncalvesova, E, Cavusoglu, Y, Fernandez, A, Chaaban, S, Bøhmer, E, Pouleur, A, Mueller, C, Tribouilloy, C, Lonn, E, A L Buraiki, J, Gniot, J, Mozheiko, M, Lelonek, M, Noè, A, Schwende, H, Bao, W, Butylin, D, Pascual-Figal, D, Transition, I, Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z, Fonseca C, Goncalvesova E, Cavusoglu Y, Fernandez A, Chaaban S, Bøhmer E, Pouleur AC, Mueller C, Tribouilloy C, Lonn E, A L Buraiki J, Gniot J, Mozheiko M, Lelonek M, Noè A, Schwende H, Bao W, Butylin D, Pascual-Figal D, and TRANSITION Investigators
- Abstract
Aims: To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF). Methods and results: TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin–angiotensin–aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1–14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from. the day of discharge was Day –1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79–1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83–0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92–1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90–2.46). Conclusions: Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks. Clinical Trial Registration: ClinicalTrials.gov ID: NCT02661217.
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- 2019
7. Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study
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Senni, M, Wachter, R, Witte, K, Straburzynska-Migaj, E, Belohlavek, J, Fonseca, C, Mueller, C, Lonn, E, Chakrabarti, A, Bao, W, Noe, A, Schwende, H, Butylin, D, Pascual-Figal, D, Transition, I, Senni M, Wachter R, Witte KK, Straburzynska-Migaj E, Belohlavek J, Fonseca C, Mueller C, Lonn E, Chakrabarti A, Bao W, Noe A, Schwende H, Butylin D, Pascual-Figal D, TRANSITION Investigators, Senni, M, Wachter, R, Witte, K, Straburzynska-Migaj, E, Belohlavek, J, Fonseca, C, Mueller, C, Lonn, E, Chakrabarti, A, Bao, W, Noe, A, Schwende, H, Butylin, D, Pascual-Figal, D, Transition, I, Senni M, Wachter R, Witte KK, Straburzynska-Migaj E, Belohlavek J, Fonseca C, Mueller C, Lonn E, Chakrabarti A, Bao W, Noe A, Schwende H, Butylin D, Pascual-Figal D, and TRANSITION Investigators
- Abstract
Aims: Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and reduced ejection fraction (HFrEF) in the ambulatory setting (PARADIGM-HF), and following stabilisation of acutely decompensated HF (ADHF) (PIONEER-HF and TRANSITION). However, data are lacking for the initiation of sacubitril/valsartan in newly diagnosed (de novo) HFrEF. Here, we assess the tolerability of initiating sacubitril/valsartan following ADHF in TRANSITION subgroups of patients with a de novo vs. prior diagnosis of HFrEF. Methods and results: TRANSITION randomised 1002 patients to pre- and post-discharge initiation of sacubitril/valsartan (analysis set n = 991, following exclusions for mis-randomisation). In this post-hoc analysis, tolerability to sacubitril/valsartan [proportion of patients achieving target dose (97/103 mg b.i.d.) at 10 weeks post-randomisation], adverse events (AEs) and serious AEs (SAEs) were compared in de novo (n = 286) and prior HFrEF (n = 705) subgroups. More de novo than prior HFrEF patients achieved target dose at Week 10 (56% vs. 45%; relative risk ratio 1.30, 95% confidence interval 1.12–1.52, P < 0.001), and fewer had SAEs and permanent treatment discontinuations. Initiation of sacubitril/valsartan did not prevent the concomitant initiation and up-titration of guideline-directed HF therapies. De novo patients showed faster and greater decreases in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin-T, and lower rates of HF and all-cause rehospitalisation vs. prior HFrEF. Conclusions: After ADHF, first-line initiation of sacubitril/valsartan in de novo HFrEF, alongside the initiation of other guideline-directed therapies, is feasible and is associated with a better risk–benefit profile than in patients with prior HFrEF. Early intervention with sacubitril/valsartan may be considered to delay disease progression in patients with de novo HFrEF. Clinical Trial Registration: ClinicalTrials.gov, NCT02661217.
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- 2019
8. NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study
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Pascual-Figal D., Wachter R., Senni M., Bao W., Noe A., Schwende H., Butylin D., Prescott M. F., Gniot J., Mozheiko M., Lelonek M., Dominguez A. R., Horacek T., Garcia del Rio E., Kobalava Z., Mueller C. E., Cavusoglu Y., Straburzynska-Migaj E., Slanina M., vom Dahl J., Ryding A., Moriarty A., Robles M. B., Villota J. N., Quintana A. G., Nitschke T., Garcia Pinilla J. M., Bonet L. A., Chaaban S., Filali zaatari S., Spinar J., Musial W., Abdelbaki K., Belohlavek J., Fehske W., Bott M. C., Hoegalmen G., Leiro M. C., Ozcan I. T., Mullens W., Kryza R., Al-Ani R., Loboz-Grudzien K., Ermoshkina L., Hojerova S., Fernandez A. A., Spinarova L., Lapp H., Bulut E., Almeida F., Vishnevsky A., Belicova M., Witte K., Wong K., Droogne W., Delforge M., Peterka M., Olbrich H. -G., Carugo S., Nessler J., McGill T. H., Huegl B., Akin I., Moreira I., Baglikov A., Thambyrajah J., Hayes C., Barrionuevo M. R., Yigit Z., Kaya H., Klimsa Z., Radvan M., Kadel C., Landmesser U., Di Tano G., Lisik M. B., Fonseca C., Oliveira L., Marques I., Santos L. M., Lenner E., Letavay P., Bueno M. G., Mota P., Wong A., Bailey K., Foley P., Hasbani E., Virani S., Massih T. A., Al-Saif S., Taborsky M., Kaislerova M., Motovska Z., Cohen A. A., Logeart D., Endemann D., Ferreira D., Brito D., Kycina P., Bollano E., Basilio E. G., Rubio L. F., Aguado M. G., Schiavi L. B., Zivano D. F., Lonn E., El Sayed A., Pouleur A. -C., Heyse A., Schee A., Polasek R., Houra M., Tribouilloy C., Seronde M. F., Galinier M., Noutsias M., Schwimmbeck P., Voigt I., Westermann D., Pulignano G., Vegsundvaag J., Da Silva Antunes J. A., Monteiro P., Stevlik J., Goncalvesova E., Hulkoova B., Castro Fernandez A. J., Davies C., Squire I., Meyer P., Sheppard R., Sahin T., Sochor K., De Geeter G., Schmeisser A., Weil J., Soares A. O., Bulashova O. V., Oshurkov A., Sunderland S. J., Glover J., Exequiel T., Decoulx E., Meyer S., Muenzel T., Frioes F., Arbolishvili G., Tokarcikova A., Karlstrom P., Trullas Vila J. C., Perez G. P., Sankaranarayanan R., Nageh T., Alasia D. C., Refaat M., Demirkan B., Al-Buraiki J., Karabsheh S., Pascual-Figal, D, Wachter, R, Senni, M, Bao, W, Noe, A, Schwende, H, Butylin, D, Prescott, M, Gniot, J, Mozheiko, M, Lelonek, M, Dominguez, A, Horacek, T, Garcia del Rio, E, Kobalava, Z, Mueller, C, Cavusoglu, Y, Straburzynska-Migaj, E, Slanina, M, vom Dahl, J, Ryding, A, Moriarty, A, Robles, M, Villota, J, Quintana, A, Nitschke, T, Garcia Pinilla, J, Bonet, L, Chaaban, S, Filali zaatari, S, Spinar, J, Musial, W, Abdelbaki, K, Belohlavek, J, Fehske, W, Bott, M, Hoegalmen, G, Leiro, M, Ozcan, I, Mullens, W, Kryza, R, Al-Ani, R, Loboz-Grudzien, K, Ermoshkina, L, Hojerova, S, Fernandez, A, Spinarova, L, Lapp, H, Bulut, E, Almeida, F, Vishnevsky, A, Belicova, M, Witte, K, Wong, K, Droogne, W, Delforge, M, Peterka, M, Olbrich, H, Carugo, S, Nessler, J, Mcgill, T, Huegl, B, Akin, I, Moreira, I, Baglikov, A, Thambyrajah, J, Hayes, C, Barrionuevo, M, Yigit, Z, Kaya, H, Klimsa, Z, Radvan, M, Kadel, C, Landmesser, U, Di Tano, G, Lisik, M, Fonseca, C, Oliveira, L, Marques, I, Santos, L, Lenner, E, Letavay, P, Bueno, M, Mota, P, Wong, A, Bailey, K, Foley, P, Hasbani, E, Virani, S, Massih, T, Al-Saif, S, Taborsky, M, Kaislerova, M, Motovska, Z, Cohen, A, Logeart, D, Endemann, D, Ferreira, D, Brito, D, Kycina, P, Bollano, E, Basilio, E, Rubio, L, Aguado, M, Schiavi, L, Zivano, D, Lonn, E, El Sayed, A, Pouleur, A, Heyse, A, Schee, A, Polasek, R, Houra, M, Tribouilloy, C, Seronde, M, Galinier, M, Noutsias, M, Schwimmbeck, P, Voigt, I, Westermann, D, Pulignano, G, Vegsundvaag, J, Da Silva Antunes, J, Monteiro, P, Stevlik, J, Goncalvesova, E, Hulkoova, B, Castro Fernandez, A, Davies, C, Squire, I, Meyer, P, Sheppard, R, Sahin, T, Sochor, K, De Geeter, G, Schmeisser, A, Weil, J, Soares, A, Bulashova, O, Oshurkov, A, Sunderland, S, Glover, J, Exequiel, T, Decoulx, E, Meyer, S, Muenzel, T, Frioes, F, Arbolishvili, G, Tokarcikova, A, Karlstrom, P, Trullas Vila, J, Perez, G, Sankaranarayanan, R, Nageh, T, Alasia, D, Refaat, M, Demirkan, B, Al-Buraiki, J, and Karabsheh, S
- Subjects
Heart Failure ,acute decompensated heart failure ,Aminobutyrates ,Biphenyl Compounds ,Aftercare ,Stroke Volume ,TRANSITION study ,Patient Discharge ,Peptide Fragments ,Angiotensin Receptor Antagonists ,Drug Combinations ,sacubitril/valsartan ,Natriuretic Peptide, Brain ,Humans ,Valsartan ,heart failure with reduced ejection fraction ,N-terminal pro–B-type natriuretic peptide - Abstract
Objectives: This study examined the effects of sacubitril/valsartan on N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response. Background: NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF). Methods: Post-hoc analysis of the TRANSITION (Comparison of Pre- and Post-discharge Initiation of Sacubitril/Valsartan Therapy in HFrEF Patients After an Acute Decompensation Event) study, including stabilized ADHF patients with reduced ejection fraction, randomized to open-label sacubitril/valsartan initiation in-hospital (pre-discharge) versus post-discharge. NT-proBNP was measured at randomization (baseline), discharge, and 4 and 10 weeks post-randomization. A favorable NT-proBNP response was defined as reduction to ≤1,000 pg/ml or >30% from baseline. Results: In patients receiving sacubitril/valsartan in-hospital, NT-proBNP was reduced by 28% at discharge, with 46% of patients obtaining favorable NT-proBNP reduction response compared with a 4% reduction and 18% favorable response rate in patients initiated post-discharge (p < 0.001). NT-proBNP was reduced similarly in patients initiating sacubitril/valsartan pre- and post-discharge (reduction at 4 weeks: 25%/22%; 10 weeks: 38%/34%) with comparable favorable response rates (46%/42% and 51%/48% at 4 and 10 weeks, respectively). NT-proBNP favorable response at 4 weeks was associated with lower risk of first heart failure (HF) rehospitalization or cardiovascular death through 26 weeks (hazard ratio: 0.57; 95% confidence interval [CI]: 0.38 to 0.86; p = 0.007). Predictors of a favorable response at 4 weeks were starting dose ≥49/51 mg twice daily, higher baseline NT-proBNP, lower baseline serum creatinine, de novo HF, no atrial fibrillation, angiotensin-converting enzyme inhibitor–naive or angiotensin receptor blocker–naive, and no prior myocardial infarction. Conclusions: In-hospital initiation of sacubitril/valsartan produced rapid reductions in NT-proBNP, statistically significant at discharge. A favorable NT-proBNP response over time was associated with a better prognosis and predicted by higher starting dose and predisposing clinical profile. (Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event [TRANSITION]; NCT02661217)
- Published
- 2020
9. EVEROLIMUS, MTORC1 INHIBITION, AND IMPACT ON HEPATOCELLULAR CARCINOMA RECURRENCE AFTER LIVER TRANSPLANTATION - 12, 24, AND 36 MONTHS DATA FROM 719 LTX RECIPIENTS: V63
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Junge, G., Fischer, L., Schemmer, P., Speziale, A., Schwende, H., Nashan, B., Neuhaus, P., and Schlitt, H. J.
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- 2014
10. mTOR Inhibition in Liver Transplantation: Do We Know How To Dose for Effective/Safe CNI Reduction?: Abstract# 714: Poster Board #-Session: P182-I
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Junge, G., Dumortier, T., Schwende, H., Kohler, S., and Fung, J.
- Published
- 2012
11. EVEROLIMUS, MTORC1 SIGNALING AND EVOLUTION OF BODY WEIGHT AFTER CARDIAC TRANSPLANTATION: 299
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Junge, G., Witte, S., Zuckermann, A., Lehmkuhl, H., Schwende, H., Wang, Z., and Kobashigawa, J.
- Published
- 2011
12. HYPERLIPIDEMIA, AN ADJUSTABLE RISK FACTOR AFTER CARDIAC TRANSPLANTATION: ANALYSIS OF 1007 HEART TRANSPLANT RECIPIENTS: 0103
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Lehmkuhl, H. B., Bara, C., Karpov, A., Schwende, H., Zuckermann, A., and Junge, G.
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- 2010
13. 1410Clinical predictors of NT-proBNP response to early initiation of sacubitril/valsartan after hospitalisation for decompensated heart failure: An analysis of the TRANSITION study
- Author
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Pascual-Figal, D, primary, Bao, W, additional, Senni, M, additional, Wachter, R, additional, Behlolavek, J, additional, Chakrabarti, A, additional, Noe, A, additional, Schwende, H, additional, Butylin, D, additional, and Prescott, M, additional
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- 2019
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14. P1637Rehospitalisations during 26 weeks of follow up from initiation of sacubitril/valsartan after acute decompensated heart failure: An analysis of the TRANSITION study
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Pascual-Figal, D, primary, Witte, K K, additional, Wachter, R, additional, Belohlavek, J, additional, Straburzynska-Migaj, E, additional, Fonseca, C, additional, Cavusoglu, Y, additional, Pouleur, A C, additional, Mueller, C, additional, Lonn, E, additional, Noe, A, additional, Schwende, H, additional, Bao, W, additional, Butylin, D, additional, and Senni, M, additional
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- 2019
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15. P773Initiation of sacubitril/valsartan and optimisation of evidence-based heart failure therapies after hospitalisation for acute decompensated heart failure: An analysis of the TRANSITION study
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Wachter, R, primary, Pascual-Figal, D, additional, Belohlavek, J, additional, Straburzynska-Migaj, E, additional, Witte, K K, additional, Fonseca, C, additional, Cavusoglu, Y, additional, Pouleur, A C, additional, Goncalvesova, E, additional, Lonn, E, additional, Noe, A, additional, Schwende, H, additional, Bao, W, additional, Butylin, D, additional, and Senni, M, additional
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- 2019
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16. In-Hospital Initiation of Sacubitril/Valsartan in Stabilised Patients with Heart Failure and Reduced Ejection Fraction Naïve to Renin-Angiotensin System Blocker: An Analysis of the Transition Study
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Wachter, R., primary, Michele, S., additional, Witte, K., additional, Straburzynska-Migaj, E., additional, Belohlavek, J., additional, Fonseca, C., additional, Mueller, C., additional, Lonn, E., additional, Bao, W., additional, Noe, A., additional, Schwende, H., additional, Butylin, D., additional, and Pascual-Figal, D., additional
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- 2019
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17. Initiation of Sacubitril/Valsartan in Patients with De Novo Heart Failure with Reduced Ejection Fraction: An Analysis of the Transition Study
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Wachter, R., primary, Michele, S., additional, Witte, K., additional, Straburzynska-Migaj, E., additional, Belohlavek, J., additional, Fonseca, C., additional, Mueller, C., additional, Lonn, E., additional, Bao, W., additional, Noe, A., additional, Schwende, H., additional, Butylin, D., additional, and Pascual-Figal, D., additional
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- 2019
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18. P6531Initiation of sacubitril/valsartan in hospitalized patients with HFrEF after hemodynamic stabilization: baseline characteristics of the TRANSITION study compared with TITRATION and PARADIGM-HF
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Senni, M, primary, Wachter, R, additional, Belohlavek, J, additional, Witte, K, additional, Strabuzynska-Migaj, E, additional, Kobalava, Z, additional, Fonseca, C, additional, Noe, A, additional, Butylin, D, additional, Schwende, H, additional, and Pascual-Figal, D, additional
- Published
- 2018
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19. mTOR Inhibition in Liver Transplantation: How to Dose for Effective/Safe CNI Reduction?
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Junge, G., primary, Dumortier, T., additional, Schwende, H., additional, and Fung, J., additional
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- 2013
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20. mTOR Inhibition in Liver Transplantation: How to Dose for Effective/Safe CNI Reduction?
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Junge, G., primary, Dumortier, T., additional, Schwende, H., additional, and Fung, J., additional
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- 2012
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21. ESTIMATION OF CARDIOVASCULAR RISK IN 1007 HEART TRANSPLANTS RECIPIENTS - THE FRAMINGHAM RISK SCORE
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Zuckermann, A., primary, Bara, C., additional, Eisen, H., additional, Karpov, A., additional, Kobashigawa, J., additional, Lehmkuhl, H. B., additional, Ross, H., additional, Schwende, H., additional, and Junge, G., additional
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- 2010
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22. PROTON PUMP INHIBITORS IMPACT CYCLOSPORINE DOSE/EXPOSURE RELATION IN DE NOVO HTXR TREATED WITH MMF OR EVEROLIMUS - EMPHASIS OF THERAPEUTIC DRUG MONITORING
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Bara, C., primary, Laufer, G., additional, Crespo, M. G., additional, Dengler, T. J., additional, Karpov, A., additional, Potena, L., additional, Schwende, H., additional, Varnous, S., additional, and Junge, G., additional
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- 2010
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23. HYPERLIPIDEMIA, A MODIFIABLE RISK FACTOR AFTER CARDIAC TRANSPLANTATION: ANALYSIS OF 1007 HEART TRANSPLANT RECIPIENTS
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Lehmkuhl, H. B., primary, Bara, C., additional, Karpov, A., additional, Schwende, H., additional, Zuckermann, A., additional, and Junge, G., additional
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- 2010
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24. BETTER RENAL ALLOGRAFT FUNCTION WITH EVEROLIMUS FACILITATED CNI REDUCTION - GRAFT TYPE, DONOR CRITERIA AND GENDER ANALYSIS
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Chan, L., primary, Lantzsch, R., additional, Riad, H., additional, Tufveson, G., additional, Cibrik, D. M., additional, Tedesco-Silva, H., additional, Schwende, H., additional, Wang, Z., additional, and Junge, G., additional
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- 2010
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25. IMPACT OF 6 DIFFERENT IMMUNOSUPPRESSIVE REGIMENS ON NEW ONSET DIABETES MELLITUS IN CARDIAC TRANSPLANT RECIPIENTS
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Lehmkuhl, H. B., primary, Bara, C., additional, Karpov, A., additional, Schwende, H., additional, Zuckermann, A., additional, and Junge, G., additional
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- 2010
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26. RATES OF CARDIAC ALLOGRAFT REJECTION IN RESPONSE TO 6 DIFFERENT IMMUNOSUPPRESSIVE REGIMENS
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Eisen, H., primary, Delgado, J., additional, Karpov, A., additional, Kobashigawa, J., additional, Lehmkuhl, H. B., additional, Pellegrini, C., additional, Schwende, H., additional, Zuckermann, A., additional, and Junge, G., additional
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- 2010
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27. 18: Efficacy Outcome in De-Novo HTxR: Comparison of 6 Immunosuppressive (IS) Regimens (ISR)
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Eisen, H.J., primary, Delgado, J.F., additional, Junge, G., additional, Karpov, A., additional, Lehmkuhl, H., additional, Pellegrini, C., additional, Kobashigawa, J., additional, Schwende, H., additional, and Zuckermann, A., additional
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- 2010
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28. 332: The Slope of Renal Function in De Novo HTxR. Can We Improve?
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Kobashigawa, J., primary, Arizon, J., additional, Dong, G., additional, Eisen, H.J., additional, Junge, G., additional, Schwende, H., additional, Zuckermann, A., additional, and Lehmkuhl, H.B., additional
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- 2010
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29. Incidences of incisional complications after de novo cardiac transplantation in AZA-, MMF- or everolimus-based regimens: a cross-study analysis on 1008 patients
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Lehmkuhl, H, primary, Bara, C, additional, Hirt, S, additional, Dengler, T, additional, Schwende, H, additional, Scheidl, S, additional, Haverich, A, additional, Hetzer, R, additional, and Barten, M, additional
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- 2010
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30. Comparative studies of cytotoxicity and the release of TNF-alpha, nitric oxide, and eicosanoids of liver macrophages treated with lipopolysaccharide and liposome-encapsulated MTP-PE.
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Dieter, P, primary, Ambs, P, additional, Fitzke, E, additional, Hidaka, H, additional, Hoffmann, R, additional, and Schwende, H, additional
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- 1995
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31. Different roles of protein kinase C-β and -δ in arachidonic acid cascade, superoxide formation and phosphoinositide hydrolysis
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Duyster, J, primary, Schwende, H, additional, Fitzke, E, additional, Hidaka, H, additional, and Dieter, P, additional
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- 1993
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32. Protein kinase C-a and -b play antagonistic roles in the differentiation process of THP-1 cells
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Dieter, P. and Schwende, H.
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- 2000
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33. MTOR INHIBITION AND EVOLUTION URINARY PROTEIN EXCRETION IN NON-RENAL TRANSPLANT PATIENTS
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Junge, G., Paolo De Simone, Saliba, Faouzi, Schwende, H., Kohler, Sven, and Fung, J.
34. Regulation of cytosolic phospholipase A2 in arachidonic acid release of rat-liver macrophages
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Ambs P, Manuela Baccarini, Schwende H, Fitzke E, and Dieter P
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Lipopolysaccharides ,Male ,Models, Biological ,Phospholipases A ,Diglycerides ,Membrane Lipids ,Cytosol ,Animals ,Phosphorylation ,Rats, Wistar ,Calcimycin ,Cells, Cultured ,Mitogen-Activated Protein Kinase 1 ,Arachidonic Acid ,Mitogen-Activated Protein Kinase 3 ,Ionophores ,Macrophages ,Phosphatidylinositol Diacylglycerol-Lyase ,Zymosan ,Rats ,Enzyme Activation ,Isoenzymes ,Lipoprotein Lipase ,Phospholipases A2 ,Liver ,Type C Phospholipases ,Calcium-Calmodulin-Dependent Protein Kinases ,Tetradecanoylphorbol Acetate ,Calcium ,Mitogen-Activated Protein Kinases ,Protein Processing, Post-Translational ,Signal Transduction
35. The Impact of mTOR Inhibition on Evolution of Renal Function and Urinary Protein Excretion-24 Months Data from 719 De Novo LTx Recipients
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Junge, G., Paolo De Simone, Saliba, F., Schwende, H., and Fung, J.
36. Impact of Everolimus on the Recurrence Rate of Hepatocellular Carcinoma after Liver Transplantation-12, 24, and 36 Months Data from 719 LTx Recipients
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Junge, G., Saliba, F., Simone, P., Fischer, L., John Fung, Dong, G., Schwende, H., and Speziale, A.
37. Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study
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W Bao, Arhit Chakrabarti, Ewa Straburzyńska-Migaj, Transition Investigators, Candida Fonseca, Michele Senni, Klaus K. Witte, Adele Noe, Rolf Wachter, Domingo A. Pascual-Figal, H Schwende, Jan Belohlavek, D Butylin, Christian Mueller, Eva Lonn, Senni, M, Wachter, R, Witte, K, Straburzynska-Migaj, E, Belohlavek, J, Fonseca, C, Mueller, C, Lonn, E, Chakrabarti, A, Bao, W, Noe, A, Schwende, H, Butylin, D, Pascual-Figal, D, and Transition, I
- Subjects
de novo ,medicine.medical_specialty ,Aftercare ,030204 cardiovascular system & hematology ,Sacubitril ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Sacubitril/valsartan ,Adverse effect ,Heart Failure ,Ejection fraction ,business.industry ,Aminobutyrates ,Biphenyl Compounds ,Tolerability ,medicine.disease ,Patient Discharge ,Drug Combinations ,Valsartan ,Heart failure ,Ambulatory ,Cardiology ,Safety ,Cardiology and Cardiovascular Medicine ,business ,TRANSITION ,Sacubitril, Valsartan ,medicine.drug - Abstract
Aims: Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and reduced ejection fraction (HFrEF) in the ambulatory setting (PARADIGM-HF), and following stabilisation of acutely decompensated HF (ADHF) (PIONEER-HF and TRANSITION). However, data are lacking for the initiation of sacubitril/valsartan in newly diagnosed (de novo) HFrEF. Here, we assess the tolerability of initiating sacubitril/valsartan following ADHF in TRANSITION subgroups of patients with a de novo vs. prior diagnosis of HFrEF. Methods and results: TRANSITION randomised 1002 patients to pre- and post-discharge initiation of sacubitril/valsartan (analysis set n = 991, following exclusions for mis-randomisation). In this post-hoc analysis, tolerability to sacubitril/valsartan [proportion of patients achieving target dose (97/103 mg b.i.d.) at 10 weeks post-randomisation], adverse events (AEs) and serious AEs (SAEs) were compared in de novo (n = 286) and prior HFrEF (n = 705) subgroups. More de novo than prior HFrEF patients achieved target dose at Week 10 (56% vs. 45%; relative risk ratio 1.30, 95% confidence interval 1.12–1.52, P < 0.001), and fewer had SAEs and permanent treatment discontinuations. Initiation of sacubitril/valsartan did not prevent the concomitant initiation and up-titration of guideline-directed HF therapies. De novo patients showed faster and greater decreases in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin-T, and lower rates of HF and all-cause rehospitalisation vs. prior HFrEF. Conclusions: After ADHF, first-line initiation of sacubitril/valsartan in de novo HFrEF, alongside the initiation of other guideline-directed therapies, is feasible and is associated with a better risk–benefit profile than in patients with prior HFrEF. Early intervention with sacubitril/valsartan may be considered to delay disease progression in patients with de novo HFrEF. Clinical Trial Registration: ClinicalTrials.gov, NCT02661217.
- Published
- 2019
38. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study
- Author
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Wachter, Rolf, Senni, Michele, Belohlavek, Jan, Straburzynska‐Migaj, Ewa, Witte, Klaus K., Kobalava, Zhanna, Fonseca, Candida, Goncalvesova, Eva, Cavusoglu, Yuksel, Fernandez, Alberto, Chaaban, Said, Bøhmer, Ellen, Pouleur, Anne‐Catherine, Mueller, Christian, Tribouilloy, Christophe, Lonn, Eva, A.L. Buraiki, Jehad, Gniot, Jacek, Mozheiko, Maria, Lelonek, Malgorzata, Noè, Adele, Schwende, Heike, Bao, Weibin, Butylin, Dmytro, Pascual‐Figal, Domingo, Dominguez, Antonio Reyes, Horacek, Thomas, del Rio, Enrique Garcia, Mueller, Christian Eugen, Straburzynska-Migaj, Ewa, Slanina, Miroslav, vom Dahl, Juergen, Ryding, Alisdair, Moriarty, Andrew, Robles, Manuel Beltran, Villota, Julio Nunez, Quintana, Antonio Garcia, Nitschke, Thorsten, Manuel Garcia Pinilla, Jose, Bonet, Luis Almenar, Filali zaatari, MD, Samia, Spinar, Jindrich, Musial, Wlodzimierz, Abdelbaki, Khaled, Fehske, Wolfgang, Bott, Michael Carlos, Hoegalmen, Geir, Leiro, Marisa Crespo, Ozcan, Ismail Turkay, Mullens, Wilfried, Kryza, Radim, Al-Ani, Riadh, Loboz-Grudzien, Krystyna, Ermoshkina, Lyudmila, Hojerova, Silvia, Fernandez, Alberto Alfredo, Spinarova, Lenka, Lapp, Harald, Bulut, Efraim, Almeida, Filipa, Vishnevsky, Alexander, Belicova, Margita, Pascual, Domingo, Witte, Klaus, Wong, Kenneth, Droogne, Walter, Delforge, Marc, Peterka, Martin, Olbrich, Hans‐Georg, Carugo, Stefano, Nessler, Jadwiga, McGill, Thao Huynh, Huegl, Burkhard, Akin, Ibrahim, Moreira, Ilidio, Baglikov, Andrey, Thambyrajah, Jeetendra, Hayes, Chris, Barrionuevo, Marcelo Raul, Yigit, Zerrin, Kaya, Hakki, Klimsa, Zdenek, Radvan, Martin, Kadel, Christoph, Landmesser, Ulf, Di Tano, Giuseppe, Lisik, Malgorzata Buksinska, Oliveira, Luis, Marques, Irene, Santos, Luis Miguel, Lenner, Egon, Letavay, Peter, Bueno, Manuel Gomez, Mota, Paula, Wong, Aaron, Bailey, Kristian, Foley, Paul, Hasbani, Eduardo, Virani, Sean, Massih, Tony Abdel, Al‐Saif, Shukri, Taborsky, Milos, Kaislerova, Marta, Motovska, Zuzana, Praha, Cohen, Aron Ariel, Logeart, Damien, Endemann, Dierk, Ferreira, Daniel, Brito, Dulce, Kycina, Peter, Bollano, Entela, Basilio, Enrique Galve, Rubio, Lorenzo Facila, Aguado, Marcos Garcia, Schiavi, Lilia Beatriz, Zivano, Daniel Francisco, Sayed, Ali El, Heyse, Alex, Schee, Alexandr, Polasek, Rostislav, Houra, Marek, Seronde, Marie France, Galinier, Michel, Noutsias, Michel, Schwimmbeck, Peter, Voigt, Ingo, Westermann, Dirk, Pulignano, Giovanni, Vegsundvaag, Johnny, Alexandre Da Silva Antunes, Jose, Monteiro, Pedro, Stevlik, Jan, Hulkoova, Beata, Juan Castro Fernandez, Antonio, Davies, Ceri, Squire, Iain, Meyer, Philippe, Sheppard, Richard, Sahin, Tayfun, Sochor, Karel, De Geeter, Guillaume, Schmeisser, Alexander, Weil, Joachim, Soares, Ana Oliveira, Vasilevna, Olga Bulashova, Oshurkov, Andrey, Sunderland, Shahid Junejo, Glover, Jason, Exequiel, Tomas, Decoulx, Eric, Meyer, Sven, Muenzel, Thomas, Frioes, Fernando, Arbolishvili, Georgy, Tokarcikova, Anna, Karlstrom, Patric, Carles Trullas Vila, Joan, Perez, Gonzalo Pena, Sankaranarayanan, Rajiv, Nageh, Thuraia, Alasia, Diego Cristian, Refaat, Marwan, Demirkan, Burcu, Al-Buraiki, Jehad, Karabsheh, Shadi, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service de pathologie cardiovasculaire, Wachter, R, Senni, M, Belohlavek, J, Straburzynska-Migaj, E, Witte, K, Kobalava, Z, Fonseca, C, Goncalvesova, E, Cavusoglu, Y, Fernandez, A, Chaaban, S, Bøhmer, E, Pouleur, A, Mueller, C, Tribouilloy, C, Lonn, E, A L Buraiki, J, Gniot, J, Mozheiko, M, Lelonek, M, Noè, A, Schwende, H, Bao, W, Butylin, D, Pascual-Figal, D, and Transition, I
- Subjects
Male ,medicine.medical_specialty ,Acute decompensated heart failure ,Tetrazoles ,Heart failure ,030204 cardiovascular system & hematology ,Sacubitril ,03 medical and health sciences ,Angiotensin Receptor Antagonists ,0302 clinical medicine ,Internal medicine ,medicine ,Clinical endpoint ,Hospitalisation ,Humans ,Sacubitril/valsartan ,Aged ,Angiotensin receptor–neprilysin inhibitor ,Heart Failure ,Ejection fraction ,Dose-Response Relationship, Drug ,business.industry ,Aminobutyrates ,Biphenyl Compounds ,Hemodynamics ,medicine.disease ,Angiotensin receptor-neprilysin inhibitor ,Patient Discharge ,3. Good health ,Discontinuation ,Drug Combinations ,Treatment Outcome ,Valsartan ,Tolerability ,Female ,Neprilysin ,business ,Cardiology and Cardiovascular Medicine ,Sacubitril, Valsartan ,medicine.drug ,Follow-Up Studies - Abstract
AIMS: To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF). METHODS AND RESULTS: TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin-angiotensin-aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1-14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day -1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79-1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83-0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92-1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90-2.46). CONCLUSIONS: Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02661217. © 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons peerReviewed
- Published
- 2019
39. Influence of diabetes on sacubitril/valsartan titration and clinical outcomes in patients hospitalized for heart failure.
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Witte KK, Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Fonseca C, Lonn E, Noè A, Schwende H, Butylin D, Chiang Y, and Pascual-Figal D
- Subjects
- Humans, Aftercare, Aminobutyrates therapeutic use, Angiotensin Receptor Antagonists therapeutic use, Biphenyl Compounds therapeutic use, Patient Discharge, Stroke Volume physiology, Tetrazoles therapeutic use, Valsartan therapeutic use, Diabetes Mellitus, Heart Failure
- Abstract
Aims: Diabetes mellitus is associated with worse outcomes and lower attainment of disease-modifying therapies in patients with heart failure with reduced ejection fraction (HFrEF). This post hoc analysis of TRANSITION compared the patterns of tolerability and uptitration of sacubitril/valsartan in patients with HFrEF stabilized after hospital admission due to acute decompensated HF depending on the presence or absence of diabetes as a co-morbidity., Methods: TRANSITION, a randomized, open-label study compared sacubitril/valsartan initiation pre-discharge vs. post-discharge (up to14 days) in 991 patients hospitalized for acutely decompensated HFrEF. The impact of diabetes status on tolerability and safety was studied at 10-week and 26-week post-randomization., Results: Among the 991 patients analysed at baseline, 460 (46.4%) had diabetes and exhibited a higher risk profile. At 10 weeks, sacubitril/valsartan target dose (97/103 mg bid) was achieved in a similar proportion of patients in each subgroup, when initiated pre-discharge or post-discharge respectively [diabetes subgroup: 47% (n = 105/226) vs. 50% (n = 115/228); relative risk ratio (RRR), 0.923; P = 0.412; non-diabetes subgroup: 45% (n = 119/267) vs. 51% (n = 133/261); RRR, 0.878; P = 0.155]. The proportions of patients achieving and maintaining either 49/51 mg or 97/103 mg bid [diabetes subgroup: 61.1% (n = 138/226) vs. 67.5% (n = 154/228); RRR, 0.909; P = 0.175; non-diabetes subgroup: 62.9% [n = 168/267] vs 69.3% [n = 181/261]; RRR, 0.906; P = 0.118] or any dose for ≥2 weeks leading to Week 10 [diabetes subgroup: 85% (n = 192/226) vs. 88.2% (n = 201/228); RRR, 0.966; P = 0.356; non-diabetes subgroup: 86.9% (n = 232/267) vs. 90.8% (n = 237/261); RRR, 0.963; P = 0.215] were also similar in each subgroup, when initiated pre-discharge or post-discharge, respectively. At 10 weeks, hypotension and renal dysfunction rates were similar, although hyperkalaemia was higher among patients with diabetes (15.9% vs. 9.5%). The rate of permanent discontinuation due to adverse events was similar in the diabetes and non-diabetes subgroups at 10 weeks, respectively: pre-discharge (7.5% vs. 7.1%) or post-discharge (5.7% vs. 4.2%). Similar patterns of uptitration and tolerability were observed at 26 weeks. Cardiac biomarkers including NT-proBNP (P < 0.005) and hs-TnT (P < 0.005) reduced significantly from baseline levels in both subgroups at Weeks 4 and 10; however, the response was greater among patients without diabetes. Mortality (diabetes vs. non-diabetes subgroups: 3.3% vs 4.0%; P = 0.438) and HF rehospitalization (diabetes vs. non-diabetes subgroups: 36.3% vs. 33.0%; P = 0.295) did not differ between the groups at 26 weeks., Conclusions: Despite a higher risk profile among patients with diabetes, sacubitril/valsartan initiation either before or shortly after discharge in hospitalized patients with HFrEF resulted in comparable rates of dose up-titration and tolerability as in those without diabetes., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
- Published
- 2023
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40. Health-related quality of life outcomes in PARAGON-HF.
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Chandra A, Polanczyk CA, Claggett BL, Vaduganathan M, Packer M, Lefkowitz MP, Rouleau JL, Liu J, Shi VC, Schwende H, Zile MR, Desai AS, Pfeffer MA, McMurray JJV, Solomon SD, and Lewis EF
- Subjects
- Humans, Quality of Life, Tetrazoles therapeutic use, Angiotensin Receptor Antagonists therapeutic use, Stroke Volume, Valsartan therapeutic use, Aminobutyrates therapeutic use, Biphenyl Compounds therapeutic use, Drug Combinations, Heart Failure drug therapy, Heart Failure chemically induced
- Abstract
Aims: Heart failure (HF) is associated with poor health-related quality of life (HRQL). Patients with HF with preserved ejection fraction (HFpEF) have similar HRQL impairment as those with reduced ejection fraction. This study describes the impact of sacubitril/valsartan on HRQL in patients with HFpEF enrolled in the PARAGON-HF trial., Methods and Results: Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQol (EQ-5D) at randomization, 4, 8 months, and annually thereafter. Changes in HRQL scores were evaluated using repeated measures models adjusted for treatment, baseline values and region. The pre-specified principal efficacy assessment was at 8 months at which time patients randomized to sacubitril/valsartan had borderline higher KCCQ clinical summary score (CSS) with least squares mean (LSM) adjusted difference of 1.0 (95% confidence interval [CI] 0.0, 2.1; p = 0.051). Including all visits up to 36 months, the LSM difference in KCCQ-CSS favoured sacubitril/valsartan with average adjusted difference of 1.1 (95% CI 0.1, 2.0; p = 0.034). Patients treated with sacubitril/valsartan had greater odds of clinically meaningful improvement (≥5-point increase) in KCCQ-CSS (odds ratio 1.31; 95% CI 1.06, 1.61) at 8 months. At 8 months, there was no significant difference in the EQ visual analogue scale between the treatment arms, but sacubitril/valsartan was associated with higher EQ-5D utility score (US-based) with LSM adjusted difference of 0.01 (95% CI 0.00, 0.02; p = 0.019)., Conclusion: Compared with valsartan, sacubitril/valsartan had a borderline benefit on KCCQ-CSS at 8 months in patients with HFpEF. This benefit became more significant when data from all visits up to 36 months were included. This modest overall benefit was also supported by greater odds of patients reporting a clinically meaningful improvement in HRQL with sacubitril/valsartan., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
- Published
- 2022
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41. NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study.
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Pascual-Figal D, Wachter R, Senni M, Bao W, Noè A, Schwende H, Butylin D, and Prescott MF
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- Aftercare, Drug Combinations, Humans, Patient Discharge, Peptide Fragments, Stroke Volume, Aminobutyrates pharmacology, Angiotensin Receptor Antagonists pharmacology, Biphenyl Compounds pharmacology, Heart Failure drug therapy, Natriuretic Peptide, Brain, Valsartan pharmacology
- Abstract
Objectives: This study examined the effects of sacubitril/valsartan on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response., Background: NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF)., Methods: Post-hoc analysis of the TRANSITION (Comparison of Pre- and Post-discharge Initiation of Sacubitril/Valsartan Therapy in HFrEF Patients After an Acute Decompensation Event) study, including stabilized ADHF patients with reduced ejection fraction, randomized to open-label sacubitril/valsartan initiation in-hospital (pre-discharge) versus post-discharge. NT-proBNP was measured at randomization (baseline), discharge, and 4 and 10 weeks post-randomization. A favorable NT-proBNP response was defined as reduction to ≤1,000 pg/ml or >30% from baseline., Results: In patients receiving sacubitril/valsartan in-hospital, NT-proBNP was reduced by 28% at discharge, with 46% of patients obtaining favorable NT-proBNP reduction response compared with a 4% reduction and 18% favorable response rate in patients initiated post-discharge (p < 0.001). NT-proBNP was reduced similarly in patients initiating sacubitril/valsartan pre- and post-discharge (reduction at 4 weeks: 25%/22%; 10 weeks: 38%/34%) with comparable favorable response rates (46%/42% and 51%/48% at 4 and 10 weeks, respectively). NT-proBNP favorable response at 4 weeks was associated with lower risk of first heart failure (HF) rehospitalization or cardiovascular death through 26 weeks (hazard ratio: 0.57; 95% confidence interval [CI]: 0.38 to 0.86; p = 0.007). Predictors of a favorable response at 4 weeks were starting dose ≥49/51 mg twice daily, higher baseline NT-proBNP, lower baseline serum creatinine, de novo HF, no atrial fibrillation, angiotensin-converting enzyme inhibitor-naive or angiotensin receptor blocker-naive, and no prior myocardial infarction., Conclusions: In-hospital initiation of sacubitril/valsartan produced rapid reductions in NT-proBNP, statistically significant at discharge. A favorable NT-proBNP response over time was associated with a better prognosis and predicted by higher starting dose and predisposing clinical profile. (Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event [TRANSITION]; NCT02661217)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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42. Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study.
- Author
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Senni M, Wachter R, Witte KK, Straburzynska-Migaj E, Belohlavek J, Fonseca C, Mueller C, Lonn E, Chakrabarti A, Bao W, Noe A, Schwende H, Butylin D, and Pascual-Figal D
- Subjects
- Aftercare, Drug Combinations, Humans, Patient Discharge, Aminobutyrates therapeutic use, Biphenyl Compounds therapeutic use, Heart Failure drug therapy, Valsartan therapeutic use
- Abstract
Aims: Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and reduced ejection fraction (HFrEF) in the ambulatory setting (PARADIGM-HF), and following stabilisation of acutely decompensated HF (ADHF) (PIONEER-HF and TRANSITION). However, data are lacking for the initiation of sacubitril/valsartan in newly diagnosed (de novo) HFrEF. Here, we assess the tolerability of initiating sacubitril/valsartan following ADHF in TRANSITION subgroups of patients with a de novo vs. prior diagnosis of HFrEF., Methods and Results: TRANSITION randomised 1002 patients to pre- and post-discharge initiation of sacubitril/valsartan (analysis set n = 991, following exclusions for mis-randomisation). In this post-hoc analysis, tolerability to sacubitril/valsartan [proportion of patients achieving target dose (97/103 mg b.i.d.) at 10 weeks post-randomisation], adverse events (AEs) and serious AEs (SAEs) were compared in de novo (n = 286) and prior HFrEF (n = 705) subgroups. More de novo than prior HFrEF patients achieved target dose at Week 10 (56% vs. 45%; relative risk ratio 1.30, 95% confidence interval 1.12-1.52, P < 0.001), and fewer had SAEs and permanent treatment discontinuations. Initiation of sacubitril/valsartan did not prevent the concomitant initiation and up-titration of guideline-directed HF therapies. De novo patients showed faster and greater decreases in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin-T, and lower rates of HF and all-cause rehospitalisation vs. prior HFrEF., Conclusions: After ADHF, first-line initiation of sacubitril/valsartan in de novo HFrEF, alongside the initiation of other guideline-directed therapies, is feasible and is associated with a better risk-benefit profile than in patients with prior HFrEF. Early intervention with sacubitril/valsartan may be considered to delay disease progression in patients with de novo HFrEF., Clinical Trial Registration: ClinicalTrials.gov, NCT02661217., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)
- Published
- 2020
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43. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study.
- Author
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Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z, Fonseca C, Goncalvesova E, Cavusoglu Y, Fernandez A, Chaaban S, Bøhmer E, Pouleur AC, Mueller C, Tribouilloy C, Lonn E, A L Buraiki J, Gniot J, Mozheiko M, Lelonek M, Noè A, Schwende H, Bao W, Butylin D, and Pascual-Figal D
- Subjects
- Aged, Angiotensin Receptor Antagonists administration & dosage, Biphenyl Compounds, Dose-Response Relationship, Drug, Drug Combinations, Female, Follow-Up Studies, Heart Failure physiopathology, Hemodynamics drug effects, Humans, Male, Neprilysin, Treatment Outcome, Valsartan, Aminobutyrates administration & dosage, Heart Failure drug therapy, Hemodynamics physiology, Patient Discharge trends, Tetrazoles administration & dosage
- Abstract
Aims: To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF)., Methods and Results: TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin-angiotensin-aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1-14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day -1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79-1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83-0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92-1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90-2.46)., Conclusions: Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks., Clinical Trial Registration: ClinicalTrials.gov ID: NCT02661217., (© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
- Published
- 2019
- Full Text
- View/download PDF
44. Formation of eicosanoids during differentiation of THP-1 cells.
- Author
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Schwende H, Fitzke E, Ambs P, and Dieter P
- Subjects
- Calcimycin pharmacology, Cell Differentiation drug effects, Dinoprostone metabolism, Gene Expression Regulation, Neoplastic drug effects, Humans, Isoenzymes biosynthesis, Isoenzymes genetics, Leukemia, Monocytic, Acute metabolism, Lipopolysaccharide Receptors biosynthesis, Lipopolysaccharide Receptors genetics, Lipopolysaccharides pharmacology, Macrophage-1 Antigen biosynthesis, Macrophage-1 Antigen genetics, Neoplasm Proteins biosynthesis, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Phagocytosis drug effects, Phospholipases A biosynthesis, Phospholipases A genetics, Superoxides metabolism, Tumor Cells, Cultured drug effects, Tumor Necrosis Factor-alpha metabolism, Cholecalciferol pharmacology, Eicosanoids biosynthesis, Leukemia, Monocytic, Acute pathology, Tetradecanoylphorbol Acetate pharmacology, Tretinoin pharmacology
- Published
- 1997
- Full Text
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45. Lipopolysaccharide and liposome-encapsulated MTP-PE-induced cytotoxicity and release of eicosanoids, tumor necrosis factor- alpha and nitric oxide in liver macrophages.
- Author
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Dieter P, Ambs P, Fitzke E, and Schwende H
- Subjects
- Acetylmuramyl-Alanyl-Isoglutamine administration & dosage, Acetylmuramyl-Alanyl-Isoglutamine pharmacology, Animals, Cells, Cultured, Diglycerides metabolism, Drug Carriers, Lipopolysaccharides pharmacology, Liposomes, Macrophages metabolism, Phosphatidylethanolamines administration & dosage, Signal Transduction drug effects, Signal Transduction physiology, Tumor Cells, Cultured, Acetylmuramyl-Alanyl-Isoglutamine analogs & derivatives, Cytotoxicity, Immunologic drug effects, Eicosanoids metabolism, Macrophage Activation drug effects, Macrophages drug effects, Nitric Oxide physiology, Phosphatidylethanolamines pharmacology, Tumor Necrosis Factor-alpha metabolism
- Published
- 1997
- Full Text
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46. Differences in the state of differentiation of THP-1 cells induced by phorbol ester and 1,25-dihydroxyvitamin D3.
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Schwende H, Fitzke E, Ambs P, and Dieter P
- Subjects
- Blotting, Western, Cell Differentiation drug effects, Cell Division drug effects, Cytosol enzymology, Dinoprostone metabolism, Enzyme Activation, Humans, Isoenzymes metabolism, Leukemia, Monocytic, Acute chemically induced, Leukemia, Monocytic, Acute metabolism, Lipopolysaccharide Receptors biosynthesis, Macrophage-1 Antigen biosynthesis, Phagocytosis drug effects, Phospholipases A metabolism, Phospholipases A2, Protein Kinase C metabolism, Superoxides metabolism, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha metabolism, Calcitriol pharmacology, Carcinogens pharmacology, Leukemia, Monocytic, Acute pathology, Tetradecanoylphorbol Acetate pharmacology
- Abstract
Human THP-1 leukemia cells differentiate along the monocytic lineage following exposure to phorbol-12-myristate-13-acetate (PMA) or 1,25-dihydroxyvitamin D3 (VD3). In the monocytic cell line THP-1, PMA treatment resulted in a more differentiated phenotype than VD3, according to adherence, loss of proliferation, phagocytosis of latex beads, and expression of CD11b and CD14. Both differentiating substances induced similar effects in the release of superoxide anions (O2-). VD3-differentiated cells did not release prostaglandin E2 (PGE2), in contrast to PMA-differentiated cells, and in PMA-differentiated cells phospholipase A2 (PLA2) activity and expression was increase. Lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha) release was higher in PMA-treated cells. PMA- but not VD3-differentiation resulted in a translocation of protein kinase C (PKC) isoenzymes to membrane fractions. Both differentiating agents up-regulated the expression of PKC isoenzymes. Whereas VD3 elevated mainly the expression of PKC-beta, PMA caused a strong increase in PKC-delta and a weak increase in PKC-alpha, PKC-epsilon, and PKC-zeta expression. These results indicate that phorbol ester and the active metabolite of vitamin D induce different signal pathways, which might result in different achievement of differentiation.
- Published
- 1996
47. Different roles of protein kinase C-beta and -delta in arachidonic acid cascade, superoxide formation and phosphoinositide hydrolysis.
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Duyster J, Schwende H, Fitzke E, Hidaka H, and Dieter P
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- Animals, Cells, Cultured, Hydrolysis, Liver cytology, Macrophages enzymology, Male, Phorbol Esters pharmacology, Rats, Rats, Wistar, Signal Transduction, Tetradecanoylphorbol Acetate pharmacology, Arachidonic Acid metabolism, Isoenzymes metabolism, Phosphatidylinositols metabolism, Protein Kinase C metabolism, Superoxides metabolism
- Abstract
In contrast with protein kinase C (PKC)-beta, PKC-delta is exclusively detectable in the membrane fraction of liver macrophages. After long-term treatment with phorbol 12-myristate 13-acetate (PMA) PKC-beta is depleted faster (within 3 h) than PKC-delta (> 7h). Simultaneously, pretreatment with PMA for 3 h inhibits the PMA- and zymosan-induced generation of superoxide and the PMA-induced formation of prostaglandin (PG) E2, whereas a preincubation of more than 7 h is required to affect the zymosan-induced release of PGE2 and inositol phosphates. These results support an involvement of PKC-beta in the PMA-induced activation of the arachidonic acid cascade and in superoxide formation and imply an involvement of PKC-delta in zymosan-induced phosphoinositide hydrolysis and PGE2 formation. Two phorbol ester derivates, sapintoxin A (SAPA) and 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPA), which have been previously reported to activate preferentially PLC-beta but not PKC-delta in vitro [Ryves, Evans, Olivier, Parker and Evans (1992) FEBS Lett. 288, 5-9], induce the formation of PGE2 and superoxide, down-regulate PKC-delta and potentiate inositol phosphate formation in parallel SAPA, but not DOPPA, down-regulates PKC-beta and inhibits the PMA-induced formation of eicosanoids and superoxide.
- Published
- 1993
- Full Text
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