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2. Prognostic significance of anaemia in patients with heart failure with preserved and reduced ejection fraction: Results from the MAGGIC individual patient data meta-analysis
- Author
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Berry, C, Poppe, K, Gamble, G, Earle, N, Ezekowitz, J, Squire, I, Mcmurray, J, Mcalister, F, Komajda, M, Swedberg, K, Maggioni, A, Ahmed, A, Whalley, G, Doughty, R, Tarantini, L, Granger, C, Køber, L, Massie, B, Pocock, S, Somaratne, J, Andersson, B, Bayes-Genis, A, Cowie, M, Cubbon, R, Gonzalez-Juanatey, J, Gorini, M, Gotsman, I, Grigorian-Shamagian, L, Guazzi, M, Kearney, M, Di Lenarda, A, Lenzen, M, Lucci, D, Macín, S, Madsen, B, Martínez-Sellés, M, Oliva, F, Rich, M, Richards, M, Senni, M, Taffet, G, Tribouilloy, C, Troughton, R, Tsutsui, H, Ariti, C, Dobson, J, Hall, C, Lainchbury, J, Hogg, K, Norrie, J, Stevenson, K, Brett, M, Pfeffer, M, Held, P, Michelson, E, Olofsson, B, Östergren, J, Yusuf, S, Torp-Pedersen, C, Scholte op Reimer, W, Boersma, E, Vantrimpont, P, Follath, F, Cleland, J, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Varela-Roman, A, Mazón-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, M, Myers, J, Arena, R, Armstrong, P, Cujec, B, Paterson, I, Wood, D, Coats, A, Thompson, S, Suresh, V, Poole-Wilson, P, Sutton, G, Robles, J, Prieto, L, Muñoa, M, Frades, E, Díaz-Castro, O, Almendral, J, Faggiano, P, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, T, Boesgaard, S, Hassager, C, Nielsen, O, Aldershvile, J, Nielsen, H, Kober, L, Perna, E, Cimbaro Canella, J, Alvarenga, P, Pantich, R, Ríos, N, Farias, E, Badaracco, J, Hansen, J, Stokholm, K, Brons, J, Husum, D, Mortensen, L, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardají, A, Pascual-Figal, D, Ordoñez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Fiol, M, Nieto, V, Macaya, C, Cinca, J, Cygankiewitz, I, Bayes De Luna, A, Newton, J, Blackledge, H, Wright, S, Kerzner, R, Gage, B, Freedland, K, Huynh, B, Rovner, A, Carney, R, Teasdale, T, Bleyer, A, Kutka, N, Luchi, R, Rusinaru, D, Mahjoub, H, Soulière, V, Lévy, F, Peltier, M, Tsuchihashi, M, Takeshita, A, Maccarthy, P, Nolan, J, Lee, A, Prescott, R, Shah, A, Brooksby, W, Fox, K, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, J, Gude, F, Berry C, Poppe KK, Gamble GD, Earle NJ, Ezekowitz JA, Squire IB, McMurray JJV, McAlister FA, Komajda M, Swedberg K, Maggioni AP, Ahmed A, Whalley GA, Doughty RN, Tarantini L, Granger C, Køber L, Massie B, Pocock S, Somaratne J, Andersson B, Bayes-Genis A, Cowie M, Cubbon R, Gonzalez-Juanatey J, Gorini M, Gotsman I, Grigorian-Shamagian L, Guazzi M, Kearney M, Di Lenarda A, Lenzen M, Lucci D, Macín S, Madsen B, Martínez-Sellés M, Oliva F, Rich M, Richards M, Senni M, Taffet G, Tribouilloy C, Troughton R, Tsutsui H, Ariti C, Dobson J, Hall C, Lainchbury J, Hogg K, Norrie J, Stevenson K, Brett M, Pfeffer MA, Held P, Michelson EL, Olofsson B, Östergren J, Yusuf S, Torp-Pedersen C, Scholte op Reimer W, Boersma E, Vantrimpont PJMJ, Follath F, Cleland J, Zwas D, Planer D, Azaz-Livshits T, Admon D, Lotan C, Keren A, Varela-Roman A, Mazón-Ramos P, Rigeiro-Veloso P, Bandin-Dieguez MA, Myers J, Arena R, Armstrong PW, Cujec B, Paterson I, Wood DA, Coats AJS, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC, Robles JAG, Prieto L, Muñoa MD, Frades E, Díaz-Castro O, Almendral J, Faggiano P, Bertoli D, Porcu M, Opasich C, Tavazzi L, Kirk V, Bay M, Parner J, Krogsgaard K, Herzog TM, Boesgaard S, Hassager C, Nielsen OW, Aldershvile J, Nielsen H, Kober L, Perna ER, Cimbaro Canella JP, Alvarenga P, Pantich R, Ríos N, Farias EF, Badaracco JR, Hansen JF, Stokholm KH, Brons J, Husum D, Mortensen LS, Vazquez R, Puig T, Fernandez-Palomeque C, Bardají A, Pascual-Figal D, Ordoñez-Llanos J, Valdes M, Gabarrus A, Pavon R, Pastor L, Fiol M, Nieto V, Macaya C, Cinca J, Cygankiewitz I, Bayes De Luna A, Newton JD, Blackledge HM, Wright SP, Kerzner R, Gage BF, Freedland KE, Huynh BC, Rovner A, Carney RM, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi RJ, Rusinaru D, Mahjoub H, Soulière V, Lévy F, Peltier M, Tsuchihashi M, Takeshita A, MacCarthy PA, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KAA, Basante P, Trillo R, Garcia-Seara J, Martinez-Sande JL, Gude F, Berry, C, Poppe, K, Gamble, G, Earle, N, Ezekowitz, J, Squire, I, Mcmurray, J, Mcalister, F, Komajda, M, Swedberg, K, Maggioni, A, Ahmed, A, Whalley, G, Doughty, R, Tarantini, L, Granger, C, Køber, L, Massie, B, Pocock, S, Somaratne, J, Andersson, B, Bayes-Genis, A, Cowie, M, Cubbon, R, Gonzalez-Juanatey, J, Gorini, M, Gotsman, I, Grigorian-Shamagian, L, Guazzi, M, Kearney, M, Di Lenarda, A, Lenzen, M, Lucci, D, Macín, S, Madsen, B, Martínez-Sellés, M, Oliva, F, Rich, M, Richards, M, Senni, M, Taffet, G, Tribouilloy, C, Troughton, R, Tsutsui, H, Ariti, C, Dobson, J, Hall, C, Lainchbury, J, Hogg, K, Norrie, J, Stevenson, K, Brett, M, Pfeffer, M, Held, P, Michelson, E, Olofsson, B, Östergren, J, Yusuf, S, Torp-Pedersen, C, Scholte op Reimer, W, Boersma, E, Vantrimpont, P, Follath, F, Cleland, J, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Varela-Roman, A, Mazón-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, M, Myers, J, Arena, R, Armstrong, P, Cujec, B, Paterson, I, Wood, D, Coats, A, Thompson, S, Suresh, V, Poole-Wilson, P, Sutton, G, Robles, J, Prieto, L, Muñoa, M, Frades, E, Díaz-Castro, O, Almendral, J, Faggiano, P, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, T, Boesgaard, S, Hassager, C, Nielsen, O, Aldershvile, J, Nielsen, H, Kober, L, Perna, E, Cimbaro Canella, J, Alvarenga, P, Pantich, R, Ríos, N, Farias, E, Badaracco, J, Hansen, J, Stokholm, K, Brons, J, Husum, D, Mortensen, L, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardají, A, Pascual-Figal, D, Ordoñez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Fiol, M, Nieto, V, Macaya, C, Cinca, J, Cygankiewitz, I, Bayes De Luna, A, Newton, J, Blackledge, H, Wright, S, Kerzner, R, Gage, B, Freedland, K, Huynh, B, Rovner, A, Carney, R, Teasdale, T, Bleyer, A, Kutka, N, Luchi, R, Rusinaru, D, Mahjoub, H, Soulière, V, Lévy, F, Peltier, M, Tsuchihashi, M, Takeshita, A, Maccarthy, P, Nolan, J, Lee, A, Prescott, R, Shah, A, Brooksby, W, Fox, K, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, J, Gude, F, Berry C, Poppe KK, Gamble GD, Earle NJ, Ezekowitz JA, Squire IB, McMurray JJV, McAlister FA, Komajda M, Swedberg K, Maggioni AP, Ahmed A, Whalley GA, Doughty RN, Tarantini L, Granger C, Køber L, Massie B, Pocock S, Somaratne J, Andersson B, Bayes-Genis A, Cowie M, Cubbon R, Gonzalez-Juanatey J, Gorini M, Gotsman I, Grigorian-Shamagian L, Guazzi M, Kearney M, Di Lenarda A, Lenzen M, Lucci D, Macín S, Madsen B, Martínez-Sellés M, Oliva F, Rich M, Richards M, Senni M, Taffet G, Tribouilloy C, Troughton R, Tsutsui H, Ariti C, Dobson J, Hall C, Lainchbury J, Hogg K, Norrie J, Stevenson K, Brett M, Pfeffer MA, Held P, Michelson EL, Olofsson B, Östergren J, Yusuf S, Torp-Pedersen C, Scholte op Reimer W, Boersma E, Vantrimpont PJMJ, Follath F, Cleland J, Zwas D, Planer D, Azaz-Livshits T, Admon D, Lotan C, Keren A, Varela-Roman A, Mazón-Ramos P, Rigeiro-Veloso P, Bandin-Dieguez MA, Myers J, Arena R, Armstrong PW, Cujec B, Paterson I, Wood DA, Coats AJS, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC, Robles JAG, Prieto L, Muñoa MD, Frades E, Díaz-Castro O, Almendral J, Faggiano P, Bertoli D, Porcu M, Opasich C, Tavazzi L, Kirk V, Bay M, Parner J, Krogsgaard K, Herzog TM, Boesgaard S, Hassager C, Nielsen OW, Aldershvile J, Nielsen H, Kober L, Perna ER, Cimbaro Canella JP, Alvarenga P, Pantich R, Ríos N, Farias EF, Badaracco JR, Hansen JF, Stokholm KH, Brons J, Husum D, Mortensen LS, Vazquez R, Puig T, Fernandez-Palomeque C, Bardají A, Pascual-Figal D, Ordoñez-Llanos J, Valdes M, Gabarrus A, Pavon R, Pastor L, Fiol M, Nieto V, Macaya C, Cinca J, Cygankiewitz I, Bayes De Luna A, Newton JD, Blackledge HM, Wright SP, Kerzner R, Gage BF, Freedland KE, Huynh BC, Rovner A, Carney RM, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi RJ, Rusinaru D, Mahjoub H, Soulière V, Lévy F, Peltier M, Tsuchihashi M, Takeshita A, MacCarthy PA, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KAA, Basante P, Trillo R, Garcia-Seara J, Martinez-Sande JL, and Gude F
- Abstract
Background: Anaemia is common among patients with heart failure (HF) and is an important prognostic marker. Aim: We sought to determine the prognostic importance of anaemia in a large multinational pooled dataset of prospectively enrolled HF patients, with the specific aim to determine the prognostic role of anaemia in HF with preserved and reduced ejection fraction (HF-PEF and HF-REF, respectively). Design: Individual person data meta-analysis. Methods: Patients with haemoglobin (Hb) data fromthe MAGGIC dataset were used. Anaemia was defined as Hb < 120 g/l in women and <130 g/l inmen. HF-PEF was defined as EF ≥ 50%; HF-REF was EF < 50%. Cox proportional hazardmodelling, with adjustment for clinically relevant variables, was undertaken to investigate factors associated with 3-year all-causemortality. Results: Thirteen thousand two hundred and ninety-five patients with HF from 19 studies (9887 with HF-REF and 3408 with HF-PEF). The prevalence of anaemia was similar among those with HF-REF and HF-PEF (42.8 and 41.6% respectively). Compared with patients with normal Hb values, those with anaemia were older, were more likely to have diabetes, ischaemic aetiology, New York Heart Association class IV symptoms, lower estimated glomerular filtration rate and were more likely to be taking diuretic and less likely to be taking a beta-blocker. Patients with anaemia had higher all-cause mortality (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.25-1.51), independent of EF group: aHR 1.67 (1.39-1.99) in HFPEF and aHR 2.49 (2.13-2.90) in HF-REF. Conclusions: Anaemia is an adverse prognostic factor in HF irrespective of EF. The prognostic importance of anaemia was greatest in patients with HF-REF.
- Published
- 2016
3. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis
- Author
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Granger, C, Massie, B, Somaratne, J, Ahmed, A, Cowie, M, Gonzalez-Juanatey, J, Gorini, M, Kearney, M, di Lenarda, A, Lenzen, M, Macin, S, Madsen, B, Maggioni, A, McAlister, F, Oliva, F, Rich, M, Richards, M, Squire, I, Taffet, G, Earle, N, Perera, K, Dobson, J, Pocock, S, Poppe, K, Whalley, G, Andersson, B, Hall, C, Richards, AM, Troughton, R, Lainchbury, J, Berry, C, Hogg, K, Norrie, J, Stevenson, K, Brett, M, McMurray, J, Pfeffer, MA, Granger, CB, Held, P, McMurray, JJV, Michelson, EL, Olofsson, B, Ostergren, J, Yusuf, S, Torp-Pedersen, C, Lenzen, MJ, Reimer, WJMS, Boersma, E, Vantrimpont, PJMJ, Follath, F, Swedberg, K, Cleland, J, Komajda, M, Gotsman, I, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Grigorian-Shamagian, L, Mazon-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, MA, Guazzi, M, Myers, J, Arena, R, McAlister, FA, Ezekowitz, J, Armstrong, PW, Cujec, B, Paterson, I, Cowie, MR, Wood, DA, Coats, AJS, Thompson, SG, Suresh, V, Poole-Wilson, PA, Sutton, GC, Martinez-Selles, M, Robles, JAG, Prieto, L, Munoa, MD, Frades, E, Diaz-Castro, O, Tarantini, L, Faggiano, P, Senni, M, Lucci, D, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Maggioni, AP, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, TM, Boesgaard, S, Hassager, C, Nielsen, OW, Aldershvile, J, Nielsen, H, Kober, L, Macin, SM, Perna, ER, Canella, JPC, Alvarenga, P, Pantich, R, Rios, N, Farias, EF, Badaracco, JR, Madsen, BK, Hansen, JF, Stokholm, KH, Brons, J, Husum, D, Mortensen, LS, Bayes-Genis, A, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardaji, A, Pascual-Figal, D, Ordonez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Almendral, J, Fiol, M, Nieto, V, Macaya, C, Cinca, J, de Luna, AB, Newton, JD, Blackledge, HM, Squire, IB, Wright, SP, Whalley, GA, Doughty, RN, Kerzner, R, Gage, BF, Huynh, BC, Rovner, A, Freedland, KE, Carney, RM, Rich, MW, Taffet, GE, Teasdale, TA, Bleyer, AJ, Kutka, NJ, Luchi, RJ, Tribouilloy, C, Rusinaru, D, Mahjoub, H, Souliere, V, Levy, F, Peltier, M, Tsutsui, H, Tsuchihashi, M, Takeshita, A, MacCarthy, PA, Kearney, MT, Cubbon, R, Nolan, J, Lee, AJ, Prescott, RJ, Shah, AM, Brooksby, WP, Fox, KAA, Varela-Roman, A, Gonzalez-Juanatey, JR, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, JL, and Gude, F
- Subjects
Meta-analysis ,Heart failure ,Prognosis - Abstract
A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF). We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF epsilon 50. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28), and have a history of hypertension (51 vs. 41). Ischaemic aetiology was less common (43 vs. 59) in patients with HF-PEF. There were 121 [95 confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95 CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95 CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40. Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.
- Published
- 2012
4. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis
- Author
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Berry C, Doughty RN, Granger C, Kober L, Massie B, McAlister F, McMurray J, Pocock S, Poppe K, Swedberg K, Somaratne J, Whalley GA, Ahmed A, Andersson B, Bayes-Genis A, Cowie M, Cubbon R, Ezekowitz J, Gonzalez-Juanatey J, Gorini M, Gotsman I, Grigorian-Shamagian L, Guazzi M, Kearney M, Komajda M, di Lenarda A, Lenzen M, Lucci D, Macin S, Madsen B, Maggioni A, Martinez-Selles M, Oliva F, Rich M, Richards M, Senni M, Squire I, Taffet G, Tarantini L, Tribouilloy C, Troughton R, Tsutsui H, Earle N, Perera K, Dobson J, Whalley G, Hall C, Richards AM, Lainchbury J, Hogg K, Norrie J, Stevenson K, Brett M, Pfeffer MA, Granger CB, Held P, McMurray JJV, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Torp-Pedersen C, Lenzen MJ, Reimer WJMS, Boersma E, Vantrimpont PJMJ, Follath F, Cleland J, Zwas D, Planer D, Azaz-Livshits T, Admon D, Lotan C, Keren A, Varela-Roman A, Mazon-Ramos P, Rigeiro-Veloso P, Bandin-Dieguez MA, Gonzalez-Juanatey JR, Myers J, Arena R, McAlister FA, Armstrong PW, Cujec B, Paterson I, Cowie MR, Wood DA, Coats AJS, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC, Robles JAG, Prieto L, Munoa MD, Frades E, Diaz-Castro O, Almendral J, Faggiano P, Bertoli D, Porcu M, Opasich C, Tavazzi L, Maggioni AP, Kirk V, Bay M, Parner J, Krogsgaard K, Herzog TM, Boesgaard S, Hassager C, Nielsen OW, Aldershvile J, Nielsen H, Macin SM, Perna ER, Canella JPC, Alvarenga P, Pantich R, Rios N, Farias EF, Badaracco JR, Madsen BK, Hansen JF, Stokholm KH, Brons J, Husum D, Mortensen LS, Vazquez R, Puig T, Fernandez-Palomeque C, Bardaji A, Pascual-Figal D, Ordonez-Llanos J, Valdes M, Gabarrus A, Pavon R, Pastor L, Fiol M, Nieto V, Macaya C, Cinca J, de Luna AB, Newton JD, Blackledge HM, Squire IB, Wright SP, Kerzner R, Gage BF, Freedland KE, Rich MW, Huynh BC, Rovner A, Carney RM, Taffet GE, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi RJ, Rusinaru D, Mahjoub H, Souliere V, Levy F, Peltier M, Tsuchihashi M, Takeshita A, MacCarthy PA, Kearney MT, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KAA, Basante P, Trillo R, Garcia-Seara J, Martinez-Sande JL, Gude F, Berry, C, Doughty, R, Granger, C, Kober, L, Massie, B, Mcalister, F, Mcmurray, J, Pocock, S, Poppe, K, Swedberg, K, Somaratne, J, Whalley, G, Ahmed, A, Andersson, B, Bayes-Genis, A, Cowie, M, Cubbon, R, Ezekowitz, J, Gonzalez-Juanatey, J, Gorini, M, Gotsman, I, Grigorian-Shamagian, L, Guazzi, M, Kearney, M, Komajda, M, di Lenarda, A, Lenzen, M, Lucci, D, Macin, S, Madsen, B, Maggioni, A, Martinez-Selles, M, Oliva, F, Rich, M, Richards, M, Senni, M, Squire, I, Taffet, G, Tarantini, L, Tribouilloy, C, Troughton, R, Tsutsui, H, Earle, N, Perera, K, Dobson, J, Hall, C, Richards, A, Lainchbury, J, Hogg, K, Norrie, J, Stevenson, K, Brett, M, Pfeffer, M, Held, P, Michelson, E, Olofsson, B, Ostergren, J, Yusuf, S, Torp-Pedersen, C, Reimer, W, Boersma, E, Vantrimpont, P, Follath, F, Cleland, J, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Varela-Roman, A, Mazon-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, M, Myers, J, Arena, R, Armstrong, P, Cujec, B, Paterson, I, Wood, D, Coats, A, Thompson, S, Suresh, V, Poole-Wilson, P, Sutton, G, Robles, J, Prieto, L, Munoa, M, Frades, E, Diaz-Castro, O, Almendral, J, Faggiano, P, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, T, Boesgaard, S, Hassager, C, Nielsen, O, Aldershvile, J, Nielsen, H, Perna, E, Canella, J, Alvarenga, P, Pantich, R, Rios, N, Farias, E, Badaracco, J, Hansen, J, Stokholm, K, Brons, J, Husum, D, Mortensen, L, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardaji, A, Pascual-Figal, D, Ordonez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Fiol, M, Nieto, V, Macaya, C, Cinca, J, de Luna, A, Newton, J, Blackledge, H, Wright, S, Kerzner, R, Gage, B, Freedland, K, Huynh, B, Rovner, A, Carney, R, Teasdale, T, Bleyer, A, Kutka, N, Luchi, R, Rusinaru, D, Mahjoub, H, Souliere, V, Levy, F, Peltier, M, Tsuchihashi, M, Takeshita, A, Maccarthy, P, Nolan, J, Lee, A, Prescott, R, Shah, A, Brooksby, W, Fox, K, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, J, and Gude, F
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Male ,medicine.medical_specialty ,Prognosi ,Heart failure ,Lower risk ,Risk Factors ,Cause of Death ,Internal medicine ,medicine ,Humans ,Meta-analysi ,Aged ,Randomized Controlled Trials as Topic ,Ejection fraction ,business.industry ,Hazard ratio ,Stroke Volume ,Atrial fibrillation ,medicine.disease ,Confidence interval ,Meta-analysis ,Cardiology ,Etiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF). Methods and results We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF ≥ 50%. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28%), and have a history of hypertension (51 vs. 41%). Ischaemic aetiology was less common (43 vs. 59%) in patients with HF-PEF. There were 121 [95% confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95% CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95% CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40%. Conclusion Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.
- Published
- 2012
5. Association of heart rate and outcomes in a broad spectrum of patients with chronic heart failure: results from the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and morbidity) program
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Castagno, Davide, Skali, H, Takeuchi, M, Swedberg, K, Yusuf, S, Granger, Cb, Michelson, El, Pfeffer, Ma, Mcmurray, Jj, Solomon, Sd, and Charm, Investigators
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Heart Failure ,Left ventricular ejection fraction ,Heart rate ,Beta adrenergic receptor blocking agent ,Atrial fibrillation ,Prognosis - Published
- 2012
6. Interaction between heart rate and effect of candesartan on mortality in a broad spectrum of patients with chronic heart failure: results from the CHARM programme
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Castagno, Davide, Skali, H, Swedberg, K, Yusuf, S, Granger, Cb, Michelson, El, Pfeffer, Ma, Solomon, Sd, and Mcmurray, J. J. V.
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Heart Failure ,Heart Failure With Preserved Ejection Fraction ,Heart rate ,Heart Failure With Reduced Ejection Fraction - Published
- 2011
7. Heart rate and outcomes in a broad spectrum of patients with chronic heart failure: results from the CHARM programme
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Castagno, Davide, Skali, H, Swedberg, K, Yusuf, S, Granger, Cb, Michelson, El, Pfeffer, Ma, Mcmurray, Jjv, and Solomon, S. D.
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Heart Failure ,Heart Rate ,Heart Failure With Preserved Ejection Fraction ,Heart Failure With Reduced Ejection Fraction - Published
- 2011
8. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis
- Author
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Berry, C, Doughty, R, Granger, C, Kober, L, Massie, B, Mcalister, F, Mcmurray, J, Pocock, S, Poppe, K, Swedberg, K, Somaratne, J, Whalley, G, Ahmed, A, Andersson, B, Bayes-Genis, A, Cowie, M, Cubbon, R, Ezekowitz, J, Gonzalez-Juanatey, J, Gorini, M, Gotsman, I, Grigorian-Shamagian, L, Guazzi, M, Kearney, M, Komajda, M, di Lenarda, A, Lenzen, M, Lucci, D, Macin, S, Madsen, B, Maggioni, A, Martinez-Selles, M, Oliva, F, Rich, M, Richards, M, Senni, M, Squire, I, Taffet, G, Tarantini, L, Tribouilloy, C, Troughton, R, Tsutsui, H, Earle, N, Perera, K, Dobson, J, Hall, C, Richards, A, Lainchbury, J, Hogg, K, Norrie, J, Stevenson, K, Brett, M, Pfeffer, M, Held, P, Michelson, E, Olofsson, B, Ostergren, J, Yusuf, S, Torp-Pedersen, C, Reimer, W, Boersma, E, Vantrimpont, P, Follath, F, Cleland, J, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Varela-Roman, A, Mazon-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, M, Myers, J, Arena, R, Armstrong, P, Cujec, B, Paterson, I, Wood, D, Coats, A, Thompson, S, Suresh, V, Poole-Wilson, P, Sutton, G, Robles, J, Prieto, L, Munoa, M, Frades, E, Diaz-Castro, O, Almendral, J, Faggiano, P, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, T, Boesgaard, S, Hassager, C, Nielsen, O, Aldershvile, J, Nielsen, H, Perna, E, Canella, J, Alvarenga, P, Pantich, R, Rios, N, Farias, E, Badaracco, J, Hansen, J, Stokholm, K, Brons, J, Husum, D, Mortensen, L, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardaji, A, Pascual-Figal, D, Ordonez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Fiol, M, Nieto, V, Macaya, C, Cinca, J, de Luna, A, Newton, J, Blackledge, H, Wright, S, Kerzner, R, Gage, B, Freedland, K, Huynh, B, Rovner, A, Carney, R, Teasdale, T, Bleyer, A, Kutka, N, Luchi, R, Rusinaru, D, Mahjoub, H, Souliere, V, Levy, F, Peltier, M, Tsuchihashi, M, Takeshita, A, Maccarthy, P, Nolan, J, Lee, A, Prescott, R, Shah, A, Brooksby, W, Fox, K, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, J, Gude, F, Berry C, Doughty RN, Granger C, Kober L, Massie B, McAlister F, McMurray J, Pocock S, Poppe K, Swedberg K, Somaratne J, Whalley GA, Ahmed A, Andersson B, Bayes-Genis A, Cowie M, Cubbon R, Ezekowitz J, Gonzalez-Juanatey J, Gorini M, Gotsman I, Grigorian-Shamagian L, Guazzi M, Kearney M, Komajda M, di Lenarda A, Lenzen M, Lucci D, Macin S, Madsen B, Maggioni A, Martinez-Selles M, Oliva F, Rich M, Richards M, Senni M, Squire I, Taffet G, Tarantini L, Tribouilloy C, Troughton R, Tsutsui H, Earle N, Perera K, Dobson J, Whalley G, Hall C, Richards AM, Lainchbury J, Hogg K, Norrie J, Stevenson K, Brett M, Pfeffer MA, Granger CB, Held P, McMurray JJV, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Torp-Pedersen C, Lenzen MJ, Reimer WJMS, Boersma E, Vantrimpont PJMJ, Follath F, Cleland J, Zwas D, Planer D, Azaz-Livshits T, Admon D, Lotan C, Keren A, Varela-Roman A, Mazon-Ramos P, Rigeiro-Veloso P, Bandin-Dieguez MA, Gonzalez-Juanatey JR, Myers J, Arena R, McAlister FA, Armstrong PW, Cujec B, Paterson I, Cowie MR, Wood DA, Coats AJS, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC, Robles JAG, Prieto L, Munoa MD, Frades E, Diaz-Castro O, Almendral J, Faggiano P, Bertoli D, Porcu M, Opasich C, Tavazzi L, Maggioni AP, Kirk V, Bay M, Parner J, Krogsgaard K, Herzog TM, Boesgaard S, Hassager C, Nielsen OW, Aldershvile J, Nielsen H, Macin SM, Perna ER, Canella JPC, Alvarenga P, Pantich R, Rios N, Farias EF, Badaracco JR, Madsen BK, Hansen JF, Stokholm KH, Brons J, Husum D, Mortensen LS, Vazquez R, Puig T, Fernandez-Palomeque C, Bardaji A, Pascual-Figal D, Ordonez-Llanos J, Valdes M, Gabarrus A, Pavon R, Pastor L, Fiol M, Nieto V, Macaya C, Cinca J, de Luna AB, Newton JD, Blackledge HM, Squire IB, Wright SP, Kerzner R, Gage BF, Freedland KE, Rich MW, Huynh BC, Rovner A, Carney RM, Taffet GE, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi RJ, Rusinaru D, Mahjoub H, Souliere V, Levy F, Peltier M, Tsuchihashi M, Takeshita A, MacCarthy PA, Kearney MT, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KAA, Basante P, Trillo R, Garcia-Seara J, Martinez-Sande JL, Gude F, Berry, C, Doughty, R, Granger, C, Kober, L, Massie, B, Mcalister, F, Mcmurray, J, Pocock, S, Poppe, K, Swedberg, K, Somaratne, J, Whalley, G, Ahmed, A, Andersson, B, Bayes-Genis, A, Cowie, M, Cubbon, R, Ezekowitz, J, Gonzalez-Juanatey, J, Gorini, M, Gotsman, I, Grigorian-Shamagian, L, Guazzi, M, Kearney, M, Komajda, M, di Lenarda, A, Lenzen, M, Lucci, D, Macin, S, Madsen, B, Maggioni, A, Martinez-Selles, M, Oliva, F, Rich, M, Richards, M, Senni, M, Squire, I, Taffet, G, Tarantini, L, Tribouilloy, C, Troughton, R, Tsutsui, H, Earle, N, Perera, K, Dobson, J, Hall, C, Richards, A, Lainchbury, J, Hogg, K, Norrie, J, Stevenson, K, Brett, M, Pfeffer, M, Held, P, Michelson, E, Olofsson, B, Ostergren, J, Yusuf, S, Torp-Pedersen, C, Reimer, W, Boersma, E, Vantrimpont, P, Follath, F, Cleland, J, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Varela-Roman, A, Mazon-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, M, Myers, J, Arena, R, Armstrong, P, Cujec, B, Paterson, I, Wood, D, Coats, A, Thompson, S, Suresh, V, Poole-Wilson, P, Sutton, G, Robles, J, Prieto, L, Munoa, M, Frades, E, Diaz-Castro, O, Almendral, J, Faggiano, P, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, T, Boesgaard, S, Hassager, C, Nielsen, O, Aldershvile, J, Nielsen, H, Perna, E, Canella, J, Alvarenga, P, Pantich, R, Rios, N, Farias, E, Badaracco, J, Hansen, J, Stokholm, K, Brons, J, Husum, D, Mortensen, L, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardaji, A, Pascual-Figal, D, Ordonez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Fiol, M, Nieto, V, Macaya, C, Cinca, J, de Luna, A, Newton, J, Blackledge, H, Wright, S, Kerzner, R, Gage, B, Freedland, K, Huynh, B, Rovner, A, Carney, R, Teasdale, T, Bleyer, A, Kutka, N, Luchi, R, Rusinaru, D, Mahjoub, H, Souliere, V, Levy, F, Peltier, M, Tsuchihashi, M, Takeshita, A, Maccarthy, P, Nolan, J, Lee, A, Prescott, R, Shah, A, Brooksby, W, Fox, K, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, J, Gude, F, Berry C, Doughty RN, Granger C, Kober L, Massie B, McAlister F, McMurray J, Pocock S, Poppe K, Swedberg K, Somaratne J, Whalley GA, Ahmed A, Andersson B, Bayes-Genis A, Cowie M, Cubbon R, Ezekowitz J, Gonzalez-Juanatey J, Gorini M, Gotsman I, Grigorian-Shamagian L, Guazzi M, Kearney M, Komajda M, di Lenarda A, Lenzen M, Lucci D, Macin S, Madsen B, Maggioni A, Martinez-Selles M, Oliva F, Rich M, Richards M, Senni M, Squire I, Taffet G, Tarantini L, Tribouilloy C, Troughton R, Tsutsui H, Earle N, Perera K, Dobson J, Whalley G, Hall C, Richards AM, Lainchbury J, Hogg K, Norrie J, Stevenson K, Brett M, Pfeffer MA, Granger CB, Held P, McMurray JJV, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Torp-Pedersen C, Lenzen MJ, Reimer WJMS, Boersma E, Vantrimpont PJMJ, Follath F, Cleland J, Zwas D, Planer D, Azaz-Livshits T, Admon D, Lotan C, Keren A, Varela-Roman A, Mazon-Ramos P, Rigeiro-Veloso P, Bandin-Dieguez MA, Gonzalez-Juanatey JR, Myers J, Arena R, McAlister FA, Armstrong PW, Cujec B, Paterson I, Cowie MR, Wood DA, Coats AJS, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC, Robles JAG, Prieto L, Munoa MD, Frades E, Diaz-Castro O, Almendral J, Faggiano P, Bertoli D, Porcu M, Opasich C, Tavazzi L, Maggioni AP, Kirk V, Bay M, Parner J, Krogsgaard K, Herzog TM, Boesgaard S, Hassager C, Nielsen OW, Aldershvile J, Nielsen H, Macin SM, Perna ER, Canella JPC, Alvarenga P, Pantich R, Rios N, Farias EF, Badaracco JR, Madsen BK, Hansen JF, Stokholm KH, Brons J, Husum D, Mortensen LS, Vazquez R, Puig T, Fernandez-Palomeque C, Bardaji A, Pascual-Figal D, Ordonez-Llanos J, Valdes M, Gabarrus A, Pavon R, Pastor L, Fiol M, Nieto V, Macaya C, Cinca J, de Luna AB, Newton JD, Blackledge HM, Squire IB, Wright SP, Kerzner R, Gage BF, Freedland KE, Rich MW, Huynh BC, Rovner A, Carney RM, Taffet GE, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi RJ, Rusinaru D, Mahjoub H, Souliere V, Levy F, Peltier M, Tsuchihashi M, Takeshita A, MacCarthy PA, Kearney MT, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KAA, Basante P, Trillo R, Garcia-Seara J, Martinez-Sande JL, and Gude F
- Abstract
Aims: A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reportedmixed resultswhether survival is similar to those patientswith heart failure and reduced EF (HF-REF). Methods and results: We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF ≥ 50%. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28%), and have a history of hypertension (51 vs. 41%). Ischaemic aetiology was less common (43 vs. 59%) in patients with HF-PEF. There were 121 [95% confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95% CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95% CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40%. Conclusion: Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.
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- 2012
9. Efficacy and safety of angiotensin receptor blockade are not modified by aspirin in patients with chronic heart failure: a cohort study from the Candesartan in Heart failure--Assessment of Reduction in Mortality and morbidity (CHARM) programme.
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Chang SM, Granger CB, Johansson PA, Kosolcharoen P, McMurray JJ, Michelson EL, Murray DR, Olofsson B, Pfeffer MA, Solomon SD, Swedberg K, Yusuf S, Dunlap ME, and CHARM Investigators
- Published
- 2010
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10. The hemoglobin A1c level as a progressive risk factor for cardiovascular death, hospitalization for heart failure, or death in patients with chronic heart failure: an analysis of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program.
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Gerstein HC, Swedberg K, Carlsson J, McMurray JJV, Michelson EL, Olofsson B, Pfeffer MA, Yusuf S, and CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) Program Investigators
- Published
- 2008
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11. An evaluation of the effects of an angiotensin receptor blocker on health-related quality of life in patients with high-normal blood pressure (prehypertension) in the Trial of Preventing Hypertension (TROPHY).
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Williams SA, Michelson EL, Cain VA, Yang M, Nesbitt SD, Egan BM, Julius S, TROPHY Study Investigators, Williams, Setareh A, Michelson, Eric L, Cain, Valerie A, Yang, Min, Nesbitt, Shawna D, Egan, Brent M, and Julius, Stevo
- Abstract
The Trial of Preventing Hypertension (TROPHY) demonstrated the feasibility of possibly reducing the incidence of hypertension with the angiotensin receptor blocker candesartan compared with placebo. The long-term benefits of pharmacologic therapy in high-normal blood pressure, or prehypertension are not known, and the long-term effect on health-related quality of life (HRQL) has not been determined. An analysis of covariance model was used to assess treatment differences from baseline in the HRQL scores using Short Form (SF)-36, and component measures at subsequent visits. Of the 809 randomized patients, 734 had both baseline and > or =1 HRQL follow-up assessment: 95% (379 of 397) of patients receiving candesartan and 91% (355 of 388) of patients receiving placebo. There were no statistically significant between-group differences in least-squares mean physical component survey and mental component survey scores or the individual scales at each scheduled visit relative to baseline values (P >.05). In TROPHY, patients with prehypertension had relatively high baseline HRQL, and HRQL was maintained with the angiotensin receptor blocker candesartan over both the 2-year treatment period and a total 4-year trial period. [ABSTRACT FROM AUTHOR]
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- 2008
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12. Efficacy and tolerability of adding an angiotensin receptor blocker in patients with heart failure already receiving an angiotensin-converting inhibitor plus aldosterone antagonist, with or without a beta blocker. Findings from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial.
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Weir RA, McMurray JJ, Puu M, Solomon SD, Olofsson B, Granger CB, Yusuf S, Michelson EL, Swedberg K, Pfeffer MA, and CHARM Investigators
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- 2008
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13. Influence of nonfatal hospitalization for heart failure on subsequent mortality in patients with chronic heart failure.
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Solomon SD, Dobson J, Pocock S, Skali H, McMurray JJ, Granger CB, Yusuf S, Swedberg K, Young JB, Michelson EL, Pfeffer MA, and Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity Investigators
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- 2007
14. Body mass index and prognosis in patients with chronic heart failure: insights from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program.
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Kenchaiah S, Pocock SJ, Wang D, Finn PV, Zornoff LA, Skali H, Pfeffer MA, Yusuf S, Swedberg K, Michelson EL, Granger CB, McMurray JJ, Solomon SD, and CHARM Investigators
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- 2007
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15. Sex differences in clinical characteristics and prognosis in a broad spectrum of patients with heart failure: results of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program.
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O'Meara E, Clayton T, McEntegart MB, McMurray JJ, Piña IL, Granger CB, Ostergren J, Michelson EL, Solomon SD, Pocock S, Yusuf S, Swedberg K, Pfeffer MA, and CHARM Investigators
- Published
- 2007
16. Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program.
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O'Meara E, Clayton T, McEntegart MB, McMurray JJ, Lang CC, Roger SD, Young JB, Solomon SD, Granger CB, Ostergren J, Olofsson B, Michelson EL, Pocock S, Yusuf S, Swedberg K, Pfeffer MA, and CHARM Committees and Investigators
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- 2006
17. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure.
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Hillege HL, Nitsch D, Pfeffer MA, Swedberg K, McMurray JJ, Yusuf S, Granger CB, Michelson EL, Ostergren J, Cornel JH, de Zeeuw D, Pocock S, van Veldhuisen DJ, and CHARM Investigators
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- 2006
18. Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients.
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Solomon SD, Anavekar N, Skali H, McMurray JJ, Swedberg K, Yusuf S, Granger CB, Michelson EL, Wang D, Pocock S, Pfeffer MA, and Candesartan in Heart Failure Reduction in Mortality (CHARM) Investigators
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- 2005
19. Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM Low-Left Ventricular Ejection Fraction Trials.
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Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, Granger CB, Hradec J, Kuch J, McKelvie RS, McMurray JJV, Michelson EL, Olofsson B, Ostergren J, Held P, Solomon SD, Yusuf S, Swedberg K, and Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity Investigators and Committees
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- 2004
20. Effect of candesartan on cause-specific mortality in heart failure patients: the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program.
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Solomon SD, Wang D, Finn P, Skali H, Zornoff L, McMurray JJV, Swedberg K, Yusuf S, Granger CB, Michelson EL, Pocock S, Pfeffer MA, Solomon, Scott D, Wang, Duolao, Finn, Peter, Skali, Hicham, Zornoff, Leonardo, McMurray, John J V, Swedberg, Karl, and Yusuf, Salim
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- 2004
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21. Evaluation of arrhythmogenicity of surgically induced endocardial versus ischemic myocardial damage
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Michelson El, Harken Ah, Moore En, and Lewis Wetstein
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,biology ,business.industry ,Fissipedia ,Ischemia ,Anterior Descending Coronary Artery ,medicine.disease ,biology.organism_classification ,Group B ,Internal medicine ,Occlusion ,cardiovascular system ,medicine ,Carnivora ,Cardiology ,Surgery ,cardiovascular diseases ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business ,Endocardium - Abstract
Ventricular tachyarrhythmias are common sequelae of ischemic myocardial damage. To assess the susceptibility to sustained ventricular tachycardia in a canine model in which endocardial excision was performed, 30 adult mongrel dogs were divided into three groups and studied in an open-chest condition, anesthetized under pentobarbital anesthesia, 7 to 14 days after undergoing one of three alternative procedures: (Group A) sham-operated controls, 10 dogs; (Group B) left ventricular endocardial excision, 10 dogs; and (Group C) myocardial infarction produced by a 2-hour occlusion and subsequent reperfusion of the left anterior descending coronary artery, 10 dogs. Using programmed ventricular pacing with two extrastimuli via plunge electrodes at 10 normal sites in the distribution of the left anterior descending coronary artery in each dog, sustained ventricular tachycardia was induced in 0/10 Group A dogs at 0/100 sites and in 0/10 Group B dogs at 0/100 sites; in contrast, in Group C, 7/10 (70%, p
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- 1984
22. Association of Heart Rate and Outcomes in a Broad Spectrum of Patients With Chronic Heart Failure: Results From the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and morbidity) Program.
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Castagno D, Skali H, Takeuchi M, Swedberg K, Yusuf S, Granger CB, Michelson EL, Pfeffer MA, McMurray JJ, Solomon SD, and CHARM Investigators
- Published
- 2012
23. The Incidence of Bradyarrhythmias and Clinical Bradyarrhythmic Events in Patients With Acute Coronary Syndromes Treated With Ticagrelor or Clopidogrel in the PLATO (Platelet Inhibition and Patient Outcomes) Trial Results of the Continuous Electrocardiographic Assessment Substudy.
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Scirica BM, Cannon CP, Emanuelsson H, Michelson EL, Harrington RA, Husted S, James S, Katus H, Pais P, Raev D, Spinar J, Steg PG, Storey RF, Wallentin L, and PLATO Investigators
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- 2011
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24. Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program.
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Sedai AS, Swedberg K, McMurray JJV, Granger CB, Yusuf S, Young JB, Dunlap ME, Solomon SD, Hainer JW, Olofsson B, Michelson EL, Pfeffer MA, and CHARM Program Investigators
- Published
- 2007
25. Feasibility of treating prehypertension with an angiotensin-receptor blocker.
- Author
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Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, Black HR, Grimm RH Jr., Messerli FH, Oparil S, Schork MA, Trial of Preventing Hypertension (TROPHY) Study Investigators, Julius, Stevo, Nesbitt, Shawna D, Egan, Brent M, Weber, Michael A, Michelson, Eric L, Kaciroti, Niko, Black, Henry R, and Grimm, Richard H Jr
- Abstract
Background: Prehypertension is considered a precursor of stage 1 hypertension and a predictor of excessive cardiovascular risk. We investigated whether pharmacologic treatment of prehypertension prevents or postpones stage 1 hypertension.Methods: Participants with repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower, or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hg, were randomly assigned to receive two years of candesartan (Atacand, AstraZeneca) or placebo, followed by two years of placebo for all. When a participant reached the study end point of stage 1 hypertension, treatment with antihypertensive agents was initiated. Both the candesartan group and the placebo group were instructed to make changes in lifestyle to reduce blood pressure throughout the trial.Results: A total of 409 participants were randomly assigned to candesartan, and 400 to placebo. Data on 772 participants (391 in the candesartan group and 381 in the placebo group; mean age, 48.5 years; 59.6 percent men) were available for analysis. During the first two years, hypertension developed in 154 participants in the placebo group and 53 of those in the candesartan group (relative risk reduction, 66.3 percent; P<0.001). After four years, hypertension had developed in 240 participants in the placebo group and 208 of those in the candesartan group (relative risk reduction, 15.6 percent; P<0.007). Serious adverse events occurred in 3.5 percent of the participants assigned to candesartan and 5.9 percent of those receiving placebo.Conclusions: Over a period of four years, stage 1 hypertension developed in nearly two thirds of patients with untreated prehypertension (the placebo group). Treatment of prehypertension with candesartan appeared to be well tolerated and reduced the risk of incident hypertension during the study period. Thus, treatment of prehypertension appears to be feasible. (ClinicalTrials.gov number, NCT00227318.). [ABSTRACT FROM AUTHOR]- Published
- 2006
26. Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial.
- Author
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Granger BB, Swedberg K, Ekman I, Granger CB, Olofsson B, McMurray JJ, Yusuf S, Michelson EL, Pfeffer MA, and CHARM investigators
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- 2005
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27. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial.
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Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJV, Michelson EL, Olofsson B, Östergren J, and CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) Investigators and Committees
- Published
- 2003
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28. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial.
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Granger CB, McMurray JJV, Yusuf S, Held P, Michelson EL, Olofsson B, Östergren J, Pfeffer MA, Swedberg K, and CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) Investigators and Committees
- Published
- 2003
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29. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial.
- Author
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McMurray JJV, Östergren J, Swedberg K, Granger CB, Held P, Michelson EL, Olofsson B, Yusuf S, Pfeffer MA, and CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) Investigators and Committees
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- 2003
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30. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme.
- Author
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Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJV, Michelson EL, Olofsson B, Östergren J, Yusuf S, CHARM (Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity) Investigators and Committees, Pfeffer, Marc A, Swedberg, Karl, Granger, Christopher B, Held, Peter, McMurray, John J V, Michelson, Eric L, Olofsson, Bertil, Ostergren, Jan, Yusuf, Salim, and Pocock, Stuart
- Abstract
Background: Patients with chronic heart failure (CHF) are at high risk of cardiovascular death and recurrent hospital admissions. We aimed to find out whether the use of an angiotensin-receptor blocker could reduce mortality and morbidity.Methods: In parallel, randomised, double-blind, controlled, clinical trials we compared candesartan with placebo in three distinct populations. We studied patients with left-ventricular ejection fraction (LVEF) 40% or less who were not receiving angiotensin-converting-enzyme inhibitors because of previous intolerance or who were currently receiving angiotensin-converting-enzyme inhibitors, and patients with LVEF higher than 40%. Overall, 7601 patients (7599 with data) were randomly assigned candesartan (n=3803, titrated to 32 mg once daily) or matching placebo (n=3796), and followed up for at least 2 years. The primary outcome of the overall programme was all-cause mortality, and for all the component trials was cardiovascular death or hospital admission for CHF. Analysis was by intention to treat.Findings: Median follow-up was 37.7 months. 886 (23%) patients in the candesartan and 945 (25%) in the placebo group died (unadjusted hazard ratio 0.91 [95% CI 0.83-1.00], p=0.055; covariate adjusted 0.90 [0.82-0.99], p=0.032), with fewer cardiovascular deaths (691 [18%] vs 769 [20%], unadjusted 0.88 [0.79-0.97], p=0.012; covariate adjusted 0.87 [0.78-0.96], p=0.006) and hospital admissions for CHF (757 [20%] vs 918 [24%], p<0.0001) in the candesartan group. There was no significant heterogeneity for candesartan results across the component trials. More patients discontinued candesartan than placebo because of concerns about renal function, hypotension, and hyperkalaemia.Interpretation: Candesartan was generally well tolerated and significantly reduced cardiovascular deaths and hospital admissions for heart failure. Ejection fraction or treatment at baseline did not alter these effects. [ABSTRACT FROM AUTHOR]- Published
- 2003
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31. Comparison of effects of nisoldipine-extended release and amlodipine in patients with systemic hypertension and chronic stable angina pectoris.
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Pepine CJ, Cooper-DeHoff RM, Weiss RJ, Koren M, Bittar N, Thadani U, Minkwitz MC, Michelson EL, Hutchinson HG, Comparative Efficacy and Safety of Nisoldipine and Amlodipine (CESNA-II) Study Investigators, Pepine, Carl J, Cooper-DeHoff, Rhonda M, Weiss, Robert J, Koren, Michael, Bittar, Neville, Thadani, Udho, Minkwitz, Margaret C, Michelson, Eric L, and Hutchinson, Howard G
- Abstract
The efficacy and safety of nisoldipine-extended release (ER) and amlodipine were compared in a 6-week multicenter, randomized, double-blind, double-dummy, parallel group, titration-to-effect trial in patients with stage 1 to 2 systemic hypertension (90 to 109 mm Hg diastolic blood pressure [BP]) and chronic stable angina pectoris. After a 3-week placebo run-in period, patients (n = 120) were randomly assigned to active treatment with either nisoldipine-ER (20 to 40 mg) or amlodipine (5 to 10 mg) once daily, titrated as necessary after 2 weeks to achieve diastolic BP <90 mm Hg. After 6 weeks, the mean reduction in systolic/diastolic BP from baseline was 15/13 mm Hg with nisoldipine-ER and 13/11 mm Hg with amlodipine (p = NS/p = NS). Both drugs resulted in similar BP responder rates (diastolic BP <90 mm Hg in 87% of patients who received nisoldipine-ER and 78% of patients on amlodipine, p = NS) and anti-ischemic responder rates (increasing exercise time >20% in 20% and 27%, respectively [p = NS], and increasing exercise time >60 seconds in 32% and 29% of patients, respectively [p = NS]. Also, after 6 weeks of active therapy, there was a similar mean increase in total exercise duration (23 seconds in the nisoldipine-ER group and 21 seconds in the amlodipine group, p = NS). Neither drug increased heart rate and both decreased frequency of anginal episodes. Adverse events were infrequent, and typically were vasodilator-related effects (including headache and peripheral edema) that occurred with somewhat higher incidence in the nisoldipine-ER group. Thus, nisoldipine-ER and amlodipine provided comparable antihypertensive and anti-ischemic efficacy, and both were generally well tolerated. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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32. The association of seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease: a prospective study.
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Haider AW, Wilson PWF, Larson MG, Evans JC, Michelson EL, Wolf PA, O'Donnell CJ, Levy D, Haider, Agha W, Wilson, Peter W F, Larson, Martin G, Evans, Jane C, Michelson, Eric L, Wolf, Philip A, O'Donnell, Christopher J, and Levy, Daniel
- Abstract
Objectives: We sought to determine whether seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus (CMV) is an independent predictor of incident cardiovascular disease.Background: Recent reports have suggested that infections may contribute to risk of cardiovascular disease. However, prospective studies of these associations in a free-living population are lacking.Methods: We measured serum H. pylori IgG, C. pneumoniae IgG and IgA, and CMV IgG levels in Framingham Heart Study cohort participants. Blood samples were drawn during the 16th biennial examination cycle (1979 to 1982) from 1,187 participants free of cardiovascular disease (mean age 69 years) and stored at -20 degrees C. A pooled primary end point of myocardial infarction, atherothrombotic stroke, and coronary heart disease deaths was studied in relation to serology. Using a Cox model, hazard ratios (HR) and 95% confidence intervals (CI) were calculated, adjusting for age, gender, and established risk factors.Results: Seropositivity to H. pylori IgG, C. pneumoniae IgG, C. pneumoniae IgA, and CMV IgG was 60%, 45%, 11%, and 69%, respectively. During 10 years of follow-up, incident cardiovascular disease occurred in 199 participants (16.8%). In age- and gender-adjusted models, H. pylori IgG (HR 1.09, 95% CI 0.81 to 1.46), C. pneumoniae IgG (HR 0.91, 95% CI 0.68 to 1.20), C. pneumoniae IgA (HR 0.65, 95% CI 0.39 to 1.07), and CMV IgG (HR 0.84, 95% CI 0.62 to 1.12) were not associated with incident cardiovascular disease. These associations were further attenuated after adjustment for risk factors including body mass index, total and high-density lipoprotein cholesterol, diabetes mellitus, smoking, and hypertension. These estimates did not change for the individual components of cardiovascular disease, and seropositivity to more than one organism did not alter these risk estimates substantially.Conclusions: In this elderly cohort, chronic H. pylori, C. pneumoniae, and CMV infections, as evidenced by seropositivity, were not associated with increased risk for cardiovascular disease. Additional studies are needed to determine the relations of chronic infections to cardiovascular disease risk in younger persons. [ABSTRACT FROM AUTHOR]- Published
- 2002
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33. Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators.
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Kloner RA, Weinberger M, Pool JL, Chrysant SG, Prasad R, Harris SM, Zyczynski TM, Leidy NK, Michelson EL, Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy Study Investigators, Kloner, R A, Weinberger, M, Pool, J L, Chrysant, S G, Prasad, R, Harris, S M, Zyczynski, T M, Leidy, N K, Michelson, E L, and Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators
- Abstract
The comparative antihypertensive efficacy and tolerability of the angiotensin II receptor blocker candesartan cilexetil and the calcium channel blocker amlodipine were evaluated in an 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study in 251 adult patients (45% women, 16% black) with mild hypertension (stage 1). Following a 4- to 5-week placebo run-in period, patients with sitting diastolic blood pressure (BP) of 90 to 99 mm Hg received candesartan cilexetil 16 mg (n = 123) or amlodipine 5 mg (n = 128) once daily. After 4 weeks of double-blind treatment, patients were uptitrated to candesartan cilexetil 32 mg or amlodipine 10 mg once daily. There were no significant differences between the candesartan cilexetil and amlodipine regimens for reducing BP; mean systolic BP/diastolic BP reductions were -15.2/-10.2 mm Hg versus -15.4/-11.3 mm Hg, respectively (p = 0.88/0.25). Overall, 79% of patients on candesartan cilexetil and 87% of those on amlodipine were controlled (diastolic BP <90 mm Hg). A total of 3.3% of patients on candesartan cilexetil discontinued treatment, compared with 9.4% of patients on amlodipine, including 2.4% versus 4.7% for adverse events and 0% versus 1.6% for peripheral edema, respectively. Peripheral edema, the prespecified primary tolerability end point, occurred with significantly greater frequency in patients on amlodipine (22.1%; mild 8.7%, moderate 11.8%, severe 1.6%) versus patients on candesartan cilexetil (8.9%; mild 8.1%, moderate 0.8%) (p = 0.005). Candesartan cilexetil and amlodipine are both highly effective in controlling BP in patients with mild hypertension. Candesartan cilexetil offers a significant tolerability advantage with respect to less risk of developing peripheral edema. [ABSTRACT FROM AUTHOR]
- Published
- 2001
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34. Effects of candesartan cilexetil in patients with severe systemic hypertension. Candesartan Cilexetil Study Investigators.
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Oparil S, Levine JH, Zuschke CA, Gradman AH, Ripley E, Jones DW, Hardison JD, Cushing DJ, Prasad R, Michelson EL, Candesartan Cilexetil Study Investigators, Oparil, S, Levine, J H, Zuschke, C A, Gradman, A H, Ripley, E, Jones, D W, Hardison, J D, Cushing, D J, and Prasad, R
- Abstract
The efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients (68% men, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Patients with sitting diastolic blood pressure (BP) > or =110 mm Hg during the placebo run-in received HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan cilexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. After 1 week of double-blind treatment, patients with sitting diastolic BP > or =90 mm Hg were uptitrated to candesartan cilexetil 16 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitration. Primary efficacy measurement was a change in trough (24+/-3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to double-blind week 4. Mean changes in systolic and diastolic BP were significantly greater with candesartan cilexetil than with placebo, -11.3/-9.1 mm Hg versus -4.1/-3.1 mm Hg, p <0.001/p <0.001, respectively. Patients with higher sitting diastolic BP at the end of the HCTZ run-in tended to have greater decreases in BP (p <0.05). Most patients (53%) receiving candesartan cilexetil were responders (diastolic BP <90 mm Hg or > or =10 mm Hg decrease) and 32% were controlled (diastolic BP <90 mm Hg). Tolerability and safety profiles were similar in the candesartan and placebo groups. In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effective and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in the United States. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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35. Effective dose range of candesartan cilexetil for systemic hypertension. Candesartan Cilexetil Study Investigators.
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Bell TP, DeQuattro V, Lasseter KC, Ruff D, Hardison JD, Cushing D, Kezer AE, Michelson EL, Candesartan Cilexetil Study Investigators, Bell, T P, DeQuattro, V, Lasseter, K C, Ruff, D, Hardison, J D, Cushing, D, Kezer, A E, and Michelson, E L
- Abstract
The results of this randomized, double-blind, placebo-controlled, forced-dose titration study in a diverse population of hypertensive patients in the US indicate that candesartan cilexetil has clinically meaningful dose-related blood pressure-lowering effects and that maximum blood pressure reduction is achieved with doses of 16 and 32 mg given once daily. This study confirms that candesartan cilexetil is a highly effective antihypertensive agent with an excellent tolerability and safety profile, without dose-related adverse effects. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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36. Effects of candesartan cilexetil in patients with systemic hypertension. Candesartan Cilexetil Study Investigators.
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Reif M, White WB, Fagan TC, Oparil S, Flanagan TL, Edwards DT, Cushing DJ, Michelson EL, Candesartan Cilexetil Study Investigators, Reif, M, White, W B, Fagan, T C, Oparil, S, Flanagan, T L, Edwards, D T, Cushing, D J, and Michelson, E L
- Abstract
The objectives of this double-blind, multicenter, randomized, parallel-arm, placebo-controlled study were to evaluate the dose-related efficacy, tolerability, and safety of candesartan cilexetil, a potent, AT1 selective, long-acting angiotensin II receptor blocker, in 365 adult patients with systemic hypertension and mean sitting diastolic blood pressure (BP) of 95 to 114 mm Hg. Patients received either placebo or candesartan cilexetil 2, 4, 8, 16, or 32 mg once daily for 8 weeks. All doses of candesartan cilexetil reduced trough (24 hours after treatment) sitting diastolic and systolic BP significantly compared with placebo (p < 0.005). A significant (p < or = 0.0001) dose response was evident, with greater decreases in BP at higher doses. Mean changes in BP were -10.7/-7.8 mm Hg and -12.6/-10.2 mm Hg in the 16- and 32-mg groups, respectively, versus -0.3/-2.6 mm Hg in the placebo group. The 16- and 32-mg doses were consistently significantly superior to placebo in antihypertensive effect with regard to all BP measurements, including peak (6 hours after treatment), trough, sitting, and standing measurements of diastolic and systolic BP. Responder rates (trough sitting diastolic BP < 90 or > or = 10 mm Hg BP decrease) were 54% and 64% for the 16- and 32-mg groups, respectively. Tolerability and safety profiles were similar to placebo at all doses. In conclusion, candesartan cilexetil administered once daily effectively reduces BP in a dose-related manner while maintaining safety and tolerability; doses of 16 and 32 mg are most effective for treatment of hypertension. [ABSTRACT FROM AUTHOR]
- Published
- 1998
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37. Can Magnetic Resonance Imaging Predict Pathologic Findings for Endometrioid Endometrial Cancer?
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Dickson Michelson EL, Kram JJF, Heslin K, Baugh D, Bamra V, Hu J, Shukla A, and Kamelle SA
- Abstract
This pilot study aimed to assess the feasibility of precisely measuring tumor diameter and myometrial invasion in patients with endometrioid endometrial cancer (EEC) using preoperative contrast-enhanced magnetic resonance imaging (MRI). Adult patients with confirmed diagnosis of complex hyperplasia with atypia or EEC were included. Three radiologists separately measured tumor diameter and myometrial invasion. Basic descriptive statistics were used to describe patient characteristics and to compare radiology- and pathology-measured tumor diameter and myometrial invasion. Using the pathology results for tumor diameter as the gold standard for comparison, at least 1 radiologist was able to predict largest tumor diameter within 5 mm for 41.7% of patients. Similarly, based on pathology results for myometrial invasion, at least 1 radiologist was able to predict myometrial invasion within 5% for 50% of patients. All radiologists were able to predict superficial (<50%) or deep (≥50%) myometrial invasion for 75% of patients, with greater sensitivity, specificity, and accuracy for deep myometrial invasion. Given variation among radiologic measurements, it is difficult to recommend preoperative MRI as a basis for measuring tumor diameter and myometrial invasion. Even so, the ability to predict superficial versus deep myometrial invasion may benefit patients with EEC for whom surgery is not a viable option or for those seeking fertility-sparing treatment options., Competing Interests: Conflicts of Interest None., (© 2020 Aurora Health Care, Inc.)
- Published
- 2020
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38. Uterine Cervical Sarcoma With a Novel RET-SPECC1L Fusion in an Adult: A Case Which Expands the Homology Between RET-rearranged and NTRK-rearranged Tumors.
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Weisman PS, Altinok M, Carballo EV, Kushner DM, Kram JJF, Ladanyi M, Chiang S, Buehler D, and Dickson Michelson EL
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- Female, Genetic Predisposition to Disease, Humans, Phenotype, Sarcoma pathology, Sarcoma surgery, Treatment Outcome, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms surgery, Young Adult, Biomarkers, Tumor genetics, Gene Fusion, Gene Rearrangement, Phosphoproteins genetics, Proto-Oncogene Proteins c-ret genetics, Receptors, Nerve Growth Factor genetics, Sarcoma genetics, Uterine Cervical Neoplasms genetics
- Published
- 2020
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39. Sexual quality of life after the treatment of gynecologic cancer: what women want.
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Hubbs JL, Dickson Michelson EL, Vogel RI, Rivard CL, Teoh DGK, and Geller MA
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- Cancer Survivors psychology, Cross-Sectional Studies, Female, Genital Neoplasms, Female physiopathology, Genital Neoplasms, Female psychology, Humans, Middle Aged, Patient Preference, Quality of Life, Sexual Behavior physiology, Sexual Behavior psychology, Sexual Dysfunction, Physiological physiopathology, Sexual Dysfunction, Physiological psychology, Sexual Health, Genital Neoplasms, Female therapy, Sexual Dysfunction, Physiological therapy
- Abstract
Purpose: While the incidence of sexual dysfunction after treatment for gynecologic malignancies is well documented, few studies describe how patients want healthcare providers to address these concerns. The objective of this study was to evaluate changes in sexual function and describe patient preferences regarding healthcare provider roles in addressing and treating sexual dysfunction in gynecologic cancer survivors., Methods: Patients undergoing gynecologic cancer treatment from 2013 to 2014 at a single University-based Gynecologic Cancer clinic were surveyed using a modified Changes in Sexual Function Questionnaire (CSFQ), along with questions relating to healthcare provider interactions and preferences., Results: Among 277 eligible patients approached to participate, 85 (30.7%) completed the survey. The mean age was 52.2 ± 12.3 years; most were non-Hispanic White (78.8%), partnered (73.2%), had endometrial or ovarian cancer (30.6% and 44.7%, respectively), and were in surveillance (57.3%). Most women (64.7%) reported much or great sexual enjoyment 1 year prior to cancer treatment which decreased to 27.4% currently; 33.3% report only rare sexual activity. There were no statistically significant differences in mean total CSFQ scores by treatment modality. A minority wanted healthcare providers to initiate sexual health discussions (25.3%); the remaining reported not wanting sexual health addressed or preferred raising the issue themselves. The most commonly cited barrier to communication was the feeling that there are more important issues to discuss with their oncology providers (46.2%)., Conclusions: While gynecologic cancer patients report changes in sexual function following cancer therapy, many believe there are other issues more paramount to be addressed. Further studies are warranted to develop better strategies for addressing sexual health in women receiving treatment for gynecologic cancers.
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- 2019
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40. Relationship Between Early and Late Nonsustained Ventricular Tachycardia and Cardiovascular Death in Patients With Acute Coronary Syndrome in the Platelet Inhibition and Patient Outcomes (PLATO) Trial.
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Bui AH, Cannon CP, Steg PG, Storey RF, Husted S, Guo J, Im K, James SK, Michelson EL, Himmelmann A, Held C, Varenhorst C, Wallentin L, and Scirica BM
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- Acute Coronary Syndrome blood, Acute Coronary Syndrome complications, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome mortality, Adenosine therapeutic use, Aged, Biomarkers blood, Cause of Death, Clopidogrel, Electrocardiography, Female, Humans, Incidence, Male, Middle Aged, Natriuretic Peptide, Brain blood, Peptide Fragments blood, Risk Assessment, Risk Factors, Tachycardia, Ventricular blood, Tachycardia, Ventricular diagnosis, Tachycardia, Ventricular mortality, Ticagrelor, Ticlopidine therapeutic use, Time Factors, Treatment Outcome, Acute Coronary Syndrome drug therapy, Adenosine analogs & derivatives, Death, Sudden, Cardiac etiology, Platelet Aggregation Inhibitors therapeutic use, Tachycardia, Ventricular etiology, Ticlopidine analogs & derivatives
- Abstract
Background: Nonsustained ventricular tachycardia (NSVT) is common after acute coronary syndrome (ACS) and a marker of increased risk of arrhythmogenic death. However, the prognostic significance of NSVT when evaluated with other contemporary risk markers and at later time points after ACS remains uncertain., Methods and Results: In the Platelet Inhibition and Patient Outcomes (PLATO) trial, continuous ECGs were performed during the first 7 days after ACS (n=2866) and repeated for another 7 days at day 30 (n=1991). Median follow-up was 1 year. There was a time-varying interaction between NSVT and cardiovascular death such that NSVT was significantly associated with increased risk within the first 30 days after randomization (22/999 [2.2%] versus 16/1825 [0.9%]; adjusted hazard ratio, 2.84; 95% confidence interval, 1.39-5.79; P=0.004) but not after 30 days (28/929 [3.0%] versus 42/1734 [2.4%]; P=0.71). Detection of NSVT during the convalescent phase (n=428/1991; 21.5%) was also associated with an increased risk of cardiovascular death, and was most marked within the first 2 months after detection (1.9% versus 0.3%; adjusted hazard ratio, 5.48; 95% confidence interval, 1.07-28.20; P=0.01), and then decreasing over time such that the relationship was no longer significant by ≈5 months after ACS., Conclusions: NSVT occurred frequently during the acute and convalescent phases of ACS. The risk of cardiovascular death associated with NSVT was the greatest during the first 30 days after presentation; however, patients with NSVT detected during the convalescent phase were also at a significantly increased risk of cardiovascular death that persisted for an additional several months after the index event., Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT00391872., (© 2016 American Heart Association, Inc.)
- Published
- 2016
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41. Considerations for assessing the potential effects of antidiabetes drugs on cardiac ventricular repolarization: A report from the Cardiac Safety Research Consortium.
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Heller S, Darpö B, Mitchell MI, Linnebjerg H, Leishman DJ, Mehrotra N, Zhu H, Koerner J, Fiszman ML, Balakrishnan S, Xiao S, Todaro TG, Hensley I, Guth BD, Michelson EL, and Sager P
- Subjects
- Brugada Syndrome, Cardiac Conduction System Disease, Dipeptidyl-Peptidase IV Inhibitors adverse effects, Electrocardiography, Glucagon-Like Peptide-1 Receptor, Glycoside Hydrolase Inhibitors, Heart Ventricles, Humans, Patch-Clamp Techniques, Receptors, Glucagon agonists, Sodium-Glucose Transporter 2 Inhibitors, Sulfonylurea Compounds adverse effects, Thiazolidinediones adverse effects, Ventricular Function, Arrhythmias, Cardiac chemically induced, Heart Conduction System abnormalities, Hypoglycemic Agents adverse effects, Long QT Syndrome chemically induced
- Abstract
Thorough QT studies conducted according to the International Council on Harmonisation E14 guideline are required for new nonantiarrhythmic drugs to assess the potential to prolong ventricular repolarization. Special considerations may be needed for conducting such studies with antidiabetes drugs as changes in blood glucose and other physiologic parameters affected by antidiabetes drugs may prolong the QT interval and thus confound QT/corrected QT assessments. This review discusses potential mechanisms for QT/corrected QT interval prolongation with antidiabetes drugs and offers practical considerations for assessing antidiabetes drugs in thorough QT studies. This article represents collaborative discussions among key stakeholders from academia, industry, and regulatory agencies participating in the Cardiac Safety Research Consortium. It does not represent regulatory policy., (Copyright © 2015 Elsevier Inc. All rights reserved.)
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- 2015
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42. Analysing recurrent hospitalizations in heart failure: a review of statistical methodology, with application to CHARM-Preserved.
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Rogers JK, Pocock SJ, McMurray JJ, Granger CB, Michelson EL, Östergren J, Pfeffer MA, Solomon SD, Swedberg K, and Yusuf S
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- Data Interpretation, Statistical, Global Health, Humans, Morbidity trends, Survival Rate trends, Heart Failure epidemiology, Hospitalization statistics & numerical data, Risk Assessment methods
- Abstract
Aims: Heart failure is characterized by recurrent hospitalizations, but often only the first event is considered in clinical trial reports. In chronic diseases, such as heart failure, analysing all events gives a more complete picture of treatment benefit. We describe methods of analysing repeat hospitalizations, and illustrate their value in one major trial., Methods and Results: The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved study compared candesartan with placebo in 3023 patients with heart failure and preserved systolic function. The heart failure hospitalization rates were 12.5 and 8.9 per 100 patient-years in the placebo and candesartan groups, respectively. The repeat hospitalizations were analysed using the Andersen-Gill, Poisson, and negative binomial methods. Death was incorporated into analyses by treating it as an additional event. The win ratio method and a method that jointly models hospitalizations and mortality were also considered. Using repeat events gave larger treatment benefits than time to first event analysis. The negative binomial method for the composite of recurrent heart failure hospitalizations and cardiovascular death gave a rate ratio of 0.75 [95% confidence interval (CI) 0.62-0.91, P = 0.003], whereas the hazard ratio for time to first heart failure hospitalization or cardiovascular death was 0.86 (95% CI 0.74-1.00, P = 0.050)., Conclusions: In patients with preserved EF, candesartan reduces the rate of admissions for worsening heart failure, to a greater extent than apparent from analysing only first hospitalizations. Recurrent events should be routinely incorporated into the analysis of future clinical trials in heart failure., (© 2013 The Authors. European Journal of Heart Failure © 2013 European Society of Cardiology.)
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- 2014
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43. Assessment of drug-induced increases in blood pressure during drug development: report from the Cardiac Safety Research Consortium.
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Sager P, Heilbraun J, Turner JR, Gintant G, Geiger MJ, Kowey PR, Mansoor GA, Mendzelevski B, Michelson EL, Stockbridge N, Weber MA, and White WB
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- Blood Pressure Monitoring, Ambulatory, Cardiovascular Diseases chemically induced, Clinical Trials as Topic, Drug Discovery, Drug Evaluation, Preclinical, Humans, Patient Safety, Risk Assessment, Blood Pressure drug effects
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This White Paper, prepared by members of the Cardiac Safety Research Consortium, discusses several important issues regarding the evaluation of blood pressure (BP) responses to drugs being developed for indications not of a direct cardiovascular (CV) nature. A wide range of drugs are associated with off-target BP increases, and both scientific attention and regulatory attention to this topic are increasing. The article provides a detailed summary of scientific discussions at a Cardiac Safety Research Consortium-sponsored Think Tank held on July 18, 2012, with the intention of moving toward consensus on how to most informatively collect and analyze BP data throughout clinical drug development to prospectively identify unacceptable CV risk and evaluate the benefit-risk relationship. The overall focus in on non-CV drugs, although many of the points also pertain to CV drugs. Brief consideration of how clinical assessment can be informed by nonclinical investigation is also outlined. These discussions present current thinking and suggestions for furthering our knowledge and understanding of off-target drug-induced BP increases and do not represent regulatory guidance., (Copyright © 2013 Mosby, Inc. All rights reserved.)
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- 2013
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44. The evaluation and management of drug effects on cardiac conduction (PR and QRS intervals) in clinical development.
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Nada A, Gintant GA, Kleiman R, Gutstein DE, Gottfridsson C, Michelson EL, Strnadova C, Killeen M, Geiger MJ, Fiszman ML, Koplowitz LP, Carlson GF, Rodriguez I, and Sager PT
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- Anti-Arrhythmia Agents pharmacology, Clinical Trials as Topic, Drug Discovery, Drug Evaluation, Preclinical, Electrocardiography, Humans, Risk Assessment, Cardiovascular Diseases physiopathology, Heart Conduction System drug effects
- Abstract
Recent advances in electrocardiographic monitoring and waveform analysis have significantly improved the ability to detect drug-induced changes in cardiac repolarization manifested as changes in the QT/corrected QT interval. These advances have also improved the ability to detect drug-induced changes in cardiac conduction. This White Paper summarizes current opinion, reached by consensus among experts at the Cardiac Safety Research Consortium, on the assessment of electrocardiogram-based safety measurements of the PR and QRS intervals, representing atrioventricular and ventricular conduction, respectively, during drug development., (Copyright © 2013 Mosby, Inc. All rights reserved.)
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- 2013
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45. Cardiac imaging approaches to evaluate drug-induced myocardial dysfunction.
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Christian JB, Finkle JK, Ky B, Douglas PS, Gutstein DE, Hockings PD, Lainee P, Lenihan DJ, Mason JW, Sager PT, Todaro TG, Hicks KA, Kane RC, Ko HS, Lindenfeld J, Michelson EL, Milligan J, Munley JY, Raichlen JS, Shahlaee A, Strnadova C, Ye B, and Turner JR
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- Cardiomyopathies chemically induced, Echocardiography, Humans, Magnetic Resonance Imaging, Radionuclide Angiography, Risk Assessment, Cardiac Imaging Techniques, Cardiomyopathies diagnosis, Cardiovascular Agents adverse effects
- Abstract
The ability to make informed benefit-risk assessments for potentially cardiotoxic new compounds is of considerable interest and importance at the public health, drug development, and individual patient levels. Cardiac imaging approaches in the evaluation of drug-induced myocardial dysfunction will likely play an increasing role. However, the optimal choice of myocardial imaging modality and the recommended frequency of monitoring are undefined. These decisions are complicated by the array of imaging techniques, which have varying sensitivities, specificities, availabilities, local expertise, safety, and costs, and by the variable time-course of tissue damage, functional myocardial depression, or recovery of function. This White Paper summarizes scientific discussions of members of the Cardiac Safety Research Consortium on the main factors to consider when selecting nonclinical and clinical cardiac function imaging techniques in drug development. We focus on 3 commonly used imaging modalities in the evaluation of cardiac function: echocardiography, magnetic resonance imaging, and radionuclide (nuclear) imaging and highlight areas for future research., (Copyright © 2012 Mosby, Inc. All rights reserved.)
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- 2012
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46. Days alive and out of hospital and the patient journey in patients with heart failure: Insights from the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) program.
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Ariti CA, Cleland JG, Pocock SJ, Pfeffer MA, Swedberg K, Granger CB, McMurray JJ, Michelson EL, Ostergren J, and Yusuf S
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- Aged, Biphenyl Compounds, Female, Heart Failure drug therapy, Heart Failure pathology, Humans, Linear Models, Male, Mortality, Randomized Controlled Trials as Topic, Severity of Illness Index, Treatment Outcome, United States, Angiotensin II Type 1 Receptor Blockers administration & dosage, Benzimidazoles administration & dosage, Heart Failure mortality, Hospitalization statistics & numerical data, Models, Statistical, Tetrazoles administration & dosage
- Abstract
Background: Conventional composite outcomes in heart failure (HF) trials, for example, time to cardiovascular death or first HF hospitalization, have recognized limitations. We propose an alternative outcome, days alive and out of hospital (DAOH), which incorporates mortality and all hospitalizations into a single measure. A refinement, the patient journey, also uses functional status (New York Heart Association [NYHA] class) measured during follow-up. The CHARM program is used to illustrate the methodology., Methods: CHARM randomized 7,599 patients with symptomatic HF to placebo or candesartan, with median follow-up of 38 months. We related DAOH and percent DAOH (ie, percentage of time spent alive and out of hospital) to treatment using linear regression adjusting for follow-up time., Results: Mean increase in DAOH for patients on candesartan versus placebo was 24.1 days (95% CI 9.8-38.3 days, P < .001). The corresponding mean increase in percent DAOH was 2.0% (95% CI 0.8%-3.1%, P < .001). These findings were dominated by reduced mortality (23 days) but enhanced by reduced time in hospital (1 day). Percent time spent in hospital because of HF was reduced by 0.10% (95% CI 0.04%-0.14%, P < .001). The patient journey analysis showed that patients in the candesartan group spent more follow-up time in NYHA classes I and II and less in NYHA class IV., Conclusions: Days alive and out of hospital, especially percent DAOH, provide a valuable tool for summarizing the overall absolute treatment effect on mortality and morbidity. In future HF trials, percent DAOH can provide a useful alternative perspective on the effects of treatment., (Copyright © 2011 Mosby, Inc. All rights reserved.)
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- 2011
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47. Baseline characteristics and outcomes of patients with heart failure receiving bronchodilators in the CHARM programme.
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Hawkins NM, Wang D, Petrie MC, Pfeffer MA, Swedberg K, Granger CB, Yusuf S, Solomon SD, Ostergren J, Michelson EL, Pocock SJ, Maggioni AP, and McMurray JJ
- Subjects
- Aged, Biphenyl Compounds, Comorbidity, Female, Heart Failure mortality, Humans, Male, Middle Aged, Prognosis, Proportional Hazards Models, Pulmonary Disease, Chronic Obstructive drug therapy, Benzimidazoles therapeutic use, Bronchodilator Agents therapeutic use, Heart Failure epidemiology, Pulmonary Disease, Chronic Obstructive epidemiology, Tetrazoles therapeutic use
- Abstract
Aims: Heart failure (HF) and chronic obstructive pulmonary disease are common partners. Bronchodilators are associated with adverse cardiovascular outcomes in patients with pulmonary disease. The outcome of patients with HF prescribed bronchodilators is poorly defined., Methods and Results: The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomized 7599 patients with symptomatic HF to receive candesartan or placebo. The relative risk conveyed by bronchodilator therapy was examined using a multivariable Cox proportional hazards model. The prevalence of bronchodilator therapy was similar in patients with reduced and preserved systolic function (respectively, 8.7 vs. 9.2%, P = 0.46). Beta-blocker utilization was markedly lower in patients receiving bronchodilators compared with those without (overall 31.9 vs. 57.6%, P < 0.0001). Bronchodilator use was associated with increased all-cause mortality [HR 1.26 (1.09-1.45), P = 0.0015], cardiovascular death [HR 1.21 (1.03-1.42), P = 0.0216], HF hospitalization [HR 1.49 (1.29-1.72), P < 0.0001], and major adverse cardiovascular events [HR 1.32 (1.17-1.76), P < 0.0001]. The adverse outcomes were consistent in patients with reduced and preserved systolic function. No significant interaction was observed between bronchodilators and beta-blockade with respect to outcomes., Conclusion: Bronchodilator use is a powerful independent predictor of worsening HF and increased mortality in a broad spectrum of patients with HF. Whether this relates to a toxic effect of bronchodilators, underlying pulmonary disease, or both is unclear and warrants further investigation.
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- 2010
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48. Albuminuria in chronic heart failure: prevalence and prognostic importance.
- Author
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Jackson CE, Solomon SD, Gerstein HC, Zetterstrand S, Olofsson B, Michelson EL, Granger CB, Swedberg K, Pfeffer MA, Yusuf S, and McMurray JJ
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- Age Distribution, Aged, Albuminuria diagnosis, Albuminuria metabolism, Angiotensin II Type 1 Receptor Blockers therapeutic use, Benzimidazoles therapeutic use, Biphenyl Compounds, Canada epidemiology, Cause of Death, Chronic Disease, Comorbidity, Creatinine metabolism, Female, Glomerular Filtration Rate, Heart Failure drug therapy, Heart Failure epidemiology, Heart Failure physiopathology, Humans, Male, Mass Screening, Multivariate Analysis, Patient Admission statistics & numerical data, Predictive Value of Tests, Prevalence, Prognosis, Proportional Hazards Models, Risk Assessment, Stroke Volume, Tetrazoles therapeutic use, United States epidemiology, Ventricular Function, Left, Albuminuria epidemiology, Albuminuria etiology, Heart Failure complications
- Abstract
Background: Increased excretion of albumin in urine might be a marker of the various pathophysiological changes that arise in patients with heart failure. Therefore our aim was to assess the prevalence and prognostic value of a spot urinary albumin to creatinine ratio (UACR) in patients with heart failure., Methods: UACR was measured at baseline and during follow-up of 2310 patients in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Programme. The prevalence of microalbuminuria and macroalbuminuria, and the predictive value of UACR for the primary composite outcome of each CHARM study--ie, death from cardiovascular causes or admission to hospital with worsening heart failure--and death from any cause were assessed., Findings: 1349 (58%) patients had a normal UACR, 704 (30%) had microalbuminuria, and 257 (11%) had macroalbuminuria. The prevalence of increased UACR was similar in patients with reduced and preserved left ventricular ejection fractions. Patients with an increased UACR were older, had more cardiovascular comorbidity, worse renal function, and a higher prevalence of diabetes mellitus than did those with normoalbuminuria. However, a high prevalence of increased UACR was still noted among patients without diabetes, hypertension, or renal dysfunction. Elevated UACR was associated with increased risk of the composite outcome and death even after adjustment for other prognostic variables including renal function, diabetes, and haemoglobin A1c. The adjusted hazard ratio (HR) for the composite outcome in patients with microalbuminuria versus normoalbuminuria was 1.43 (95% CI 1.21-1.69; p<0.0001) and for macroalbuminuria versus normoalbuminuria was 1.75 (1.39-2.20; p<0.0001). The adjusted values for death were 1.62 (1.32-1.99; p<0.0001) for microalbuminuria versus normoalbuminuria, and 1.76 (1.32-2.35; p=0.0001) for macroalbuminuria versus normoalbuminuria. Treatment with candesartan did not reduce or prevent the development of excessive excretion of urinary albumin., Interpretation: Increased UACR is a powerful and independent predictor of prognosis in heart failure., Funding: AstraZeneca.
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- 2009
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49. Predictors of development of diabetes in patients with chronic heart failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program.
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Preiss D, Zetterstrand S, McMurray JJ, Ostergren J, Michelson EL, Granger CB, Yusuf S, Swedberg K, Pfeffer MA, Gerstein HC, and Sattar N
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- Aged, Blood Pressure, Body Mass Index, Chronic Disease, Female, Follow-Up Studies, Glycated Hemoglobin analysis, Heart Failure epidemiology, Heart Failure mortality, Humans, Hypertension epidemiology, Male, Middle Aged, Models, Statistical, Odds Ratio, Regression Analysis, Smoking epidemiology, Ventricular Function, Left, Diabetes Mellitus epidemiology, Heart Failure complications
- Abstract
Objective: The purpose of this study was to identify predictors of incident diabetes during follow-up of nondiabetic patients with chronic heart failure (CHF) in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program., Research Design and Methods: A total of 1,620 nondiabetic patients had full baseline datasets. We compared baseline demographic, medication, and laboratory data for patients who did or did not develop diabetes and conducted logistic regression and receiver operator characteristic curve analyses., Results: Over a median period of 2.8 years, 126 of the 1,620 patients (7.8%) developed diabetes. In multiple logistic regression analysis, the following baseline characteristics were independently associated with incident diabetes in decreasing order of significance by stepwise selection: higher A1C (odds ratio [OR] 1.78 per 1 SD increase; P < 0.0001), higher BMI (OR 1.64 per 1 SD increase; P < 0.0001), lipid-lowering therapy (OR 2.05; P = 0.0005), lower serum creatinine concentration (OR 0.68 per 1 SD increase; P = 0.0018), diuretic therapy (OR 4.81; P = 0.003), digoxin therapy (OR 1.65; P = 0.022), higher serum alanine aminotransferase concentration (OR 1.15 per 1 SD increase; P = 0.027), and lower age (OR 0.81 per 1 SD increase; P = 0.048). Using receiver operating characteristic curve analysis, A1C and BMI yielded areas under the curve of 0.723 and 0.712, respectively, increasing to 0.788 when combined. Addition of other variables independently associated with diabetes risk minimally improved prediction of diabetes., Conclusions: In nondiabetic patients with CHF in CHARM, A1C and BMI were the strongest predictors of the development of diabetes. Other minor predictors in part reflected CHF severity or drug-associated diabetes risk. Identifying patients with CHF at risk of diabetes through simple criteria appears possible and could enable targeted preventative measures.
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- 2009
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50. Liver function abnormalities and outcome in patients with chronic heart failure: data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program.
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Allen LA, Felker GM, Pocock S, McMurray JJ, Pfeffer MA, Swedberg K, Wang D, Yusuf S, Michelson EL, and Granger CB
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- Aged, Alanine Transaminase blood, Alkaline Phosphatase blood, Aspartate Aminotransferases blood, Bilirubin blood, Chronic Disease, Female, Heart Failure complications, Heart Failure mortality, Hospitalization, Humans, Liver Diseases complications, Liver Diseases diagnosis, Male, Middle Aged, Prognosis, Proportional Hazards Models, Serum Albumin analysis, Ventricular Function, Left, Heart Failure physiopathology, Liver Function Tests
- Abstract
Aims: The prevalence and importance of liver function test (LFT) abnormalities in a large contemporary cohort of heart failure patients have not been systematically evaluated., Methods and Results: We characterized the LFTs of 2679 patients with symptomatic chronic heart failure from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity program (CHARM). We used multivariable modelling to assess the relationships between baseline LFT values and long-term outcomes. Liver function test abnormalities were common in patients with chronic heart failure, ranging from alanine aminotransferase elevation in 3.1% of patients to low albumin in 18.3% of patients; total bilirubin was elevated in 13.0% of patients. In multivariable analysis, elevated total bilirubin was the strongest LFT predictor of adverse outcome for both the composite outcome of cardiovascular death or heart failure hospitalization (HR 1.21 per 1 SD increase, P<0.0001) and all-cause mortality (HR 1.19 per 1 SD increase, P<0.0001). Even after adjustment for other variables, elevated total bilirubin was one of the strongest independent predictors of poor prognosis (by global chi-square)., Conclusion: Bilirubin is independently associated with morbidity and mortality. Changes in total bilirubin may offer insight into the underlying pathophysiology of chronic heart failure.
- Published
- 2009
- Full Text
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