@article{8093156,
  abstract     = {{Background: In patients with heart failure, beta-blochade has improved morbidity and left-ventricular function, but the impact on survival is uncertain. We investigated the efficacy of bisoprolol, a beta(1) selective adrenoceptor blocker in decreasing all-cause mortality in chronic heart failure. 
Methods: In a multicentre double-blind randomised placebo-controlled trial in Europe, we enrolled 2647 symptomatic patients in New York Heart Association class III or IV, with left-ventricular ejection fraction of 35% or less receiving standard therapy with diuretics and inhibitors of angiotensin-converting enzyme. We randomly assigned patients bisoprolol 1.25 mg (n=1327) or placebo (n=1320) daily, the drug being progressively increased to a maximum of 10 mg per day. Patients were followed up for a mean of 1.3 years. Analysis was by intention to treat. 
Findings: CIBIS-II was stopped early, after the second interim analysis, because bisoprolol showed a significant mortality benefit. All-cause mortality was significantly lower with bisoprolol than on placebo (156 [11.8%] vs 228 [17.3%] deaths with a hazard ratio of 0.66 (95% CI 0.54-0.81, p<0.0001). There were significantly fewer sudden deaths among patients on bisoprolol than in those on placebo (48 [3.6%] vs 83 [6.3%] deaths), with a hazard ratio of 0.56 (0.39-0.80, p=0.0011). Treatment effects were independent of the severity or cause of heart failure. 
Interpretation: beta-blocker therapy had benefits for survival in stable heart-failure patients. Results should not, however, be extrapolated to patients with severe class IV symptoms and recent instability because safety and efficacy has not been established in these patients.}},
  author       = {{Lechat, P and Brunhuber, KW and Hofmann, R and Kuhn, P and Nesser, HJ and Slany, J and Weihs, W and Wiedermann, C and Wimmer, H and van Mieghem, W and Boland, J and Chaudron, JM and Jordaens, Luc and Melchior, JP and Aschermann, M and Bruthansl, J and Hradec, M and Kolbel, F and Semrad, B and Haghfelt, T and Fischer-Hansen, J and Goetzsche, CO and Hildebrandt, P and Kassis, E and Rasmussen, V and Rokkedal, J and Thomassen, A and Groundstroem, K and Uusimaa, P and Le Heuzey, JY and Aumont, MC and Aupetit, JF and Baille, N and Baudouy, P and Belin, A and Bonneau, A and Bonneric, G and Bousser, JP and Citron, B and Dary, P and Decoulx, E and De Groote, P and Denolle, T and Dievart, F and Duriez, P and Eicher, JC and Enjuto, G and Ferriere, M and Fournier, E and Garandeau, M and Gauthier, J and Genest, M and Gerbe, A and Godenir, JP and Guillot, B and Guillot, JP and Guillot, P and Heno, P and d'Ivernois, C and Jean, M and Kacet, S and Kalle, R and Komajda, M and Lacroix, A and Lallemand, R and Lardoux, H and Marquet, M and Martin, M and Martin, O and Mery, D and Mossaz, R and Mothes, P and Olive, T and Ostorero, M and Paganelli, F and Page, E and Pauly-Laubry, C and Puel, J and Rousseau, JF and Roux, JJ and Schenowitz, A and Sourdais, K and Tremel, F and Verdun, A and Witchiz, S and Wolf, JE and Hombach, V and Assmann, I and Beyer, T and Bischoff, KO and Darius, H and Ertl, G and Fleck, E and Forster, K and Freytag, F and Gleichmann, U and Haasis, R and Henssge, R and Hey, D and Hesse, P and Hofs, T and Keck, M and Klein, H and Kromer, ET and Kruls-Munch, J and Luderitz, B and Maisch, B and Mitrovic, V and Neubauer, S and Osterziel, KJ and Simon, H and Spitzer, SG and Stohring, R and Taubert, G and Teichmann, W and Theisen, K and Wende, W and Wieser, H and Zotz, R and Preda, I and Csanady, M and Cserhalmi, L and Edes, I and Gesztesi, T and Karpati, P and Simon, K and Tarjan, J and Fogari, R and Tramarin, R and Galie, N and Giani, P and Milanese, U and Scalvini, S and Scrutinio, D and Sechi, LA and Tettamanti, F and De Vito, F and Crean, P and McCann, H and Mulcahy, D and Sugrue, D and van Hoogenhuyze, DCA and van der Burgh, PH and Ciampricotti, R and van Dantzig, JM and DenHartog, FR and Henneman, JA and van Kesteren, HAM and Kragten, JA and Liem, KL and Limburg, A and van der Linde, MR and Linssen, GCM and Pasteuning, H and Penn, HJAM and Van Rossum, P and Schaafsma, HJ and Schelling, A and Sloos, R and Wesdorp, JCL and Korewicki, J and Achremczyk, P and Czestockowska, E and Dowgird, M and Dyduszynski, A and Gorski, J and Ilmurzynska, K and Janicki, K and Kornacewicz-Jach, Z and Kraska, T and Krzeminska-Pakula, M and Kuch, J and Nartowicz, E and Petelenz, T and Piwowarska, W and Rawczynska-Englert, I and Ruzyllo, W and Swiatecka, G and Tendera, M and Wierzchowiecki, M and Wodniecki, J and Wojciechowoski, D and Wrabec, K and Wysocki, H and Gomes, RS and Ceia, MF and Lousada, N and Campos, JMM and Providencia, LA and de Moura, ALZC and Marejev, VJ and Aronov, DM and Arutjunov, GP and Bart, BJ and Basechikin, SS and Belenkov, JN and Beloussov, JB and Bokeria, OA and Charchogljan, RA and Doschytsin, V and Fedorova, TA and Glezer, MG and Gorbachenkov, A and Gorshkov, VA and Gospodarenko, AL and Ivashkin, VT and Ivleva, AJ and Kyrichenko, AA and Lavrov, AA and Lazebnik, LB and Marynov, A and Mazaev, VP and Polejev, NR and Shpektor, A and Sidorenko, BA and Sobolev, KE and Starodoubtsev, AK and Storozhakhov, GI and Syrkin, AL and Zodionchenko, VS and Zvereva, TV and Murin, J and Kaliska, G and Rybar, R and Valle, V and Artaza, M and Conthe, P and Cruz, JM and Garcia-Moll, M and Lopez-Sendon, JL and Martinez, A and Monzon, F and Ribas, M and Roig, E and Roldan, I and Hoglund, C and Ekdahl, S and Hjelmaeus, L and Lindberg, K and Lofdahl, P and Ulvenstam, G and Warselius, L and Follath, F and Anghern, W and Dubach, P and Erne, P and Gallino, A and Moccetti, T and Bridges, A and Adgey, J and Ambepitiya, G and Boon, N and Boyle, RM and Cowley, AJ and Cripps, T and Davies, MK and Dunn, F and Findlay, J and Forsey, P and Fyfe, T and Gould, B and Greenwood, TW and Hubner, P and Khan, S and Lewis, P and Mackay, A and Maltz, M and McArthur, J and McLeod, A and McLeod, D and Metcalfe, M and Millar-Craig, M and Mills, P and Nelson, JK and Nicholls, D and Oakley, GD and Patterson, DLH and Pohl, JEF and Ray, S and Silke, B and Wilkinson, PR and Jmouro, AV}},
  issn         = {{0140-6736}},
  journal      = {{LANCET}},
  keywords     = {{HEART-RATE-VARIABILITY,BETA-BLOCKADE,CLINICAL-TRIALS,FAILURE,MORTALITY,MORBIDITY}},
  language     = {{eng}},
  number       = {{9146}},
  pages        = {{9--13}},
  title        = {{The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial}},
  volume       = {{353}},
  year         = {{1999}},
}

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