Journal ArticleDOI
Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction
Bertram Pitt,Willem J. Remme,Faiez Zannad,James D. Neaton,Felipe Martinez,Barbara Roniker,Richard Bittman,Steve Hurley,Jay H. Kleiman,Marjorie Gatlin +9 more
Reads0
Chats0
TLDR
The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.Abstract:
background Aldosterone blockade reduces mortality and morbidity among patients with severe heart failure. We conducted a double-blind, placebo-controlled study evaluating the effect of eplerenone, a selective aldosterone blocker, on morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. methods Patients were randomly assigned to eplerenone (25 mg per day initially, titrated to a maximum of 50 mg per day; 3313 patients) or placebo (3319 patients) in addition to optimal medical therapy. The study continued until 1012 deaths occurred. The primary end points were death from any cause and death from cardiovascular causes or hospitalization for heart failure, acute myocardial infarction, stroke, or ventricular arrhythmia. results During a mean follow-up of 16 months, there were 478 deaths in the eplerenone group and 554 deaths in the placebo group (relative risk, 0.85; 95 percent confidence interval, 0.75 to 0.96; P=0.008). Of these deaths, 407 in the eplerenone group and 483 in the placebo group were attributed to cardiovascular causes (relative risk, 0.83; 95 percent confidence interval, 0.72 to 0.94; P = 0.005). The rate of the other primary end point, death from cardiovascular causes or hospitalization for cardiovascular events, was reduced by eplerenone (relative risk, 0.87; 95 percent confidence interval, 0.79 to 0.95; P=0.002), as was the secondary end point of death from any cause or any hospitalization (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.98; P=0.02). There was also a reduction in the rate of sudden death from cardiac causes (relative risk, 0.79; 95 percent confidence interval, 0.64 to 0.97; P=0.03). The rate of serious hyperkalemia was 5.5 percent in the eplerenone group and 3.9 percent in the placebo group (P = 0.002), whereas the rate of hypokalemia was 8.4 percent in the eplerenone group and 13.1 percent in the placebo group (P<0.001). conclusions The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.read more
Citations
More filters
Journal ArticleDOI
Current treatment options in (peri)myocarditis and inflammatory cardiomyopathy.
B. Maisch,S. Pankuweit +1 more
TL;DR: The epidemiologic shift in pathogenetic agents in the last 20 years is analyzed, the role of innate and aquired immunity including the T- and B-cell driven immune responses are analyzed and the potential of stem cell therapy has to be tested in future trials.
Journal ArticleDOI
How robust are clinical trials in heart failure
TL;DR: The 'fragility index' (FI) offers an additional, easy to understand metric, which augments the standard reporting of boundary P-values for statistical significance, and helps in the interpretation of the robustness of the results of RCTs.
Journal ArticleDOI
Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics
Luc Roumen,Marijn P. A. Sanders,K. Pieterse,Peter A. J. Hilbers,Ralf Plate,Erica M. G. Custers,Marcel E. de Gooyer,Jos F.M. Smits,Ilona P. E. Beugels,Judith M. A. Emmen,Harry C. J. Ottenheijm,Dirk Leysen,Johannes Jozeph Robertus Maria Hermans +12 more
TL;DR: Investigating the inhibitors in the human CYP11B models using molecular docking and molecular dynamics simulations was able to predict a similar trend in potency for the inhibitors as found in the in vitro assays, and it was possible to understand the enantioselectivity of the human enzymes for the inhibitor fadrazole.
Journal ArticleDOI
Impact of mineralocorticoid receptor antagonists on the risk of sudden cardiac death in patients with heart failure and left-ventricular systolic dysfunction: an individual patient-level meta-analysis of three randomized-controlled trials.
Xavier Rossello,Xavier Rossello,Cono Ariti,Cono Ariti,Stuart J. Pocock,Stuart J. Pocock,João Pedro Ferreira,Nicolas Girerd,John J.V. McMurray,Dirk J. van Veldhuisen,Bertram Pitt,Faiez Zannad +11 more
TL;DR: MRAs reduce the risk for SCD by 23% in patients with heart failure and LVSD, and the use of MRAs, on top of other evidence-based medications, should be optimized.
Journal ArticleDOI
Mineralocorticoid receptor blockade prevents Western diet-induced diastolic dysfunction in female mice.
Brian Bostick,Javad Habibi,Vincent G. DeMarco,Guanghong Jia,Timothy L. Domeier,Michelle D. Lambert,Annayya R. Aroor,Ravi Nistala,Shawn B. Bender,Mona Garro,Melvin R. Hayden,Lixin Ma,Camila Manrique,James R. Sowers +13 more
TL;DR: A novel blood pressure-independent effect of MR antagonism as a strategy to prevent diet-induced diastolic dysfunction in women is supported, demonstrating that WD-induced DD is associated with increased oxidant stress, fibrosis, and immune dysregulation.
References
More filters
Journal ArticleDOI
Prediction of Creatinine Clearance from Serum Creatinine
Donald W. Cockcroft,M H Gault +1 more
TL;DR: A formula has been developed to predict Creatinine clearance from serum creatinine (Scr) in adult males: Ccr = (140 – age) (wt kg)/72 × Scr (mg/100ml) (15% less i).
Journal ArticleDOI
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.
Bertram Pitt,Faiez Zannad,Willem J. Remme,Robert J. Cody,Alain Castaigne,Alfonso Perez,Jolie Palensky,Janet Wittes +7 more
TL;DR: Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure.
Journal ArticleDOI
The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure
Bertram Pitt,Faiez Zannad,Willem J. Remme,Robert J. Cody,Alain Castaigne,Alfonso Perez,Jolie Palensky,Janet Wittes +7 more
The effect of spironolactone on morbidity and mortality in patients with severe heart failure
B Ertram P Itt,F Aiez Z Annad,J. R Emme,R Obert C Ody,A Lain C Astaigne,A Lfonso P Erez,J Olie P Alensky,J Anet W Ittes +7 more
Journal ArticleDOI
Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial.
TL;DR: In patients treated long-term after an acute myocardial infarction complicated by left-ventricular systolic dysfunction, carvedilol reduced the frequency of all-cause and cardiovascular mortality, and recurrent, non-fatal myocardia infarctions.
Related Papers (5)
Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. results of the survival and ventricular enlargement trial
Marc A. Pfeffer,Eugene Braunwald,Lemuel A. Moyé,Lofty L. Basta,Edward J. Brown,Thomas E. Cuddy,Barry R. Davis,Edward M. Geltman,Steven Goldman,Greg C. Flaker,Marc Klein,Gervasio A. Lamas,Milton Packer,Jacques R. Rouleau,Jean L. Rouleau,John D. Rutherford,John H. Wertheimer,C. Morton Hawkins +17 more
Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)
Åke Hjalmarson,Sidney Goldstein,Björn Fagerberg,Hans Wedel,Finn Waagstein,John Kjekshus,John Wikstrand,G. Westergren,M. Thimell,D. El Allaf,Jiri Vitovec,J. Aldershvile,M. Halinen,Rainer Dietz,K. L. Neuhaus,András Jánosi,Gudmundur Thorgeirsson,P. Dunselman,Lars Gullestad,J. Kuch,Johan Herlitz,Peter Rickenbacher,Stephen G. Ball,Stephen S. Gottlieb,Prakash Deedwania,G. Vandenhoven,I. Nováková,S. Danker,M. Lundström,W. Meyer-Sabellek,I. Balla,M. Sveinsdottir,B. Dorhout,A. Hildebrandt,I. Szczurko,C. Larsson,E. Bucher,E. Scott,D. Dwyer,D. G. Julian,David L. DeMets,K. Chatterjee,J. Feyzi,S. Lehto,P. Karpati,W. Motz,O. Samuelsson,J. W. Viersma,B. Andersson,C. Berthe,J. M. Boutefeu,G. Boxho,P. Decroly,J. P. Derbaudrenghien,J. Pirlet,Philip D. Henry,G. Heyndrickx,L. Missault,M. Nannan,P. Timmermans,J. L. Vachiery,W. Van Mieghem,J. L. Vandenbossche,K. Dvorák,M. Herold,Jaromír Hradec,A. Kána,P. Petr,J. Rybka,J. Smíd,P. Svítil,J. Toman,E. Agner,O. Amtorp,K. Egstrup,P. Eliasen,C. O. Gotzsche,P. Hildebrandt,A. Johannesen,P. Kaiser-Nielsen,H. Nielsen,P. E. Nielsen,F. Pedersen,J. Rokkedal Nielsen,K. Skagen,T. Honkanen,E. Hussi,J. Juvonen,H. Jääskeläinen,J. Rinne,T. Salonen,D. Andresen,H. Berwing,Bethge,Beythien,Bischoff,Bundschu,Daniel,Darius,Delius,Drude,Dingerkus,Dück,Eichler,Fach,A. Förster,Girth,Goss,Hahn,Hambrecht,G. F. Hauf,Heinemann,Hepp,Janka,Klocke,Konz,B. Krosse,Kühlkamp,Lewek,B. Lüderitz,Löbe,Maier,Melchior,Müller,Mäurer,Nast,Neuhaus,Obst,Odemar,K. E. von Olshausen,Pomykaj,K. J.G. Schmailzl,Schrader,Schröder,P. L. Schwimmbeck,M. Sigmund,Simon,Strasser,Thilo,Vöhringer,H. Völler,Weibrodt,Wirtz,István Czuriga,M. Hetey,A. Katona,M. Lengyel,A. Nyárádi,A. Rednik,K. Sándori,P. Szabó,J. Tarján,J. Tenczer,S. Timar,P. Vályi,G. Veress,K. Zámolyi,B. Oze,Ge Thorgeirsson,Gu Thorgeirsson,P. J.L.M. Bernink,A. C. Bredero,R. Breedveld,P. N.W.M. Breuls,J. J.J. Bucx,Jan H. Cornel,P. A. de Milliano,Peter H.J.M. Dunselman,B. J.B. Hamer,N. Holwerda,J. Hoogsteen,J. C.A. Hoorntje,Johannes A. Kragten,A. H. Liem,G. Linssen,H. R. Michels,A. R. Ramdat Misier,H. J. Schaafsma,P. Sijbring,R. J.T. Taverne,L. H.J. Van Kempen,R. Van Stralen,P. J. Van Veldhuisen,M. J. Veerhoek,C. J.P.J. Werter,J. C.L. Wesdorp,A. R. Willems,A. J.A.M. Withagen,P. A.G. Zwart,R. Bjornerheim,M. Dahle,Kenneth Dickstein,G. S. Froland,T. Gundersen,K. Hofsoy,T. L. Hole,T. Johansen,J. Mannsverk,P. Nesje,T. M. Omland,C. Sjödin,Peter K. Smith,H. A. Tjonndal,O. Vikesdal,K. Waage,Adamus,K. Jaworska,P. Kolodziej,Z. Kornacewicz-Jach,M. Krzemiñska-Pakula,J. W. Piotrowski,W. Piwowarska,A. Stogowski,J. Wodniecki,K. Wrabec,P. Ahlström,S. Ekdahl,L. O. Hemmingson,L. Holmberg,B. Lernfelt,H. Nilsson B Widgren,K. Ångman,P. Erne,P. Mohacsi,R. Polikar,H. Schläpfer,P. Batin,K. E. Berkin,T. S. Callaghan,J. Forfar,Michael P. Frenneaux,R A Greenbaum,M. Maltz,D. Murdoch,G. Reynolds,J. Stephens,Allan D. Struthers,J. Swan,G. Tildesley,A. Abbasi,P. Alagona,J. Alderman,M. Alipour,J. L. Anderson,Z. Ansari,M. Ashraf,B. T. Beanblossom,S. Bennett,D. Benvenuti,Martin R. Berk,R. Bhalla,Seth Bilazarian,K. F. Browne,C. MBuchter,R. Carlson,C. J. Carlson,K. Danisa,Ira Dauber,Marcus A. Dewood,G. Dennish,D. M. Denny,R. DiBianco,P. M. Diller,Mark E. Dunlap,K. Dowd,A. Edmiston,M. El Shahawy,Uri Elkayam,J. Farnham,P. Fenster,S. Friedman,T. Heywood,J. P. Galichia,Michael R. Geller,Jalal K. Ghali,Mihai Gheorghiade,T. Giles,R. Gillespe,G. Goldberg,M. C. Goldberg,D. A. Goldscher,G. P. Gooden,M. Goodman,L. Goodman,J. Gorwit,Shmuel Gottlieb,A. Gradman,D. Grech,T. Hack,J. H. Hall,M. T. Hattenhauer,M. B. Higginbotham,S. Hutchins,M. Imburgia,B. J. Iteld,B. Jackson,S. Jafri,W. Jauch,S. Jennison,B. H. Kahn,W. Kao,K. Kaplan,Ronald P. Karlsberg,Harold L. Kennedy,J. J. Kennedy,L. Kirkegaard,D. H. Kraus,K. LaBresh,L. Lalonde,M. F. Lesser,R. Levites,M. Levy,R. K. Lewis,Irving K. Loh,H. Madyoon,F. Maislos,Douglas L. Mann,G. L. Maurice,A. Nisar,W. Old,J. D. Pappas,K. Phadke,S. Promisloff,A. M. Rashkow,B. Reeves,J. H. Rosen,M. Rotman,T. Saleem,S. V. Savran,R. Shah,Y. Shalev,J. Shanes,M. O'Shaughnessy,B. Silverman,Richard M. Steingart,L. Swenson,K. Syed,U. Thadani,R. D. Thorsen,M. J. Tonkon,R. Touchon,G. Uhl,K. J. Vaska,S. G. Wagner,C. J. Weaver,Robert J. Weiss,W. J. Wickemeyer,H. J. Willens,J. R. Wilson,R. Wright,L. Yellen +350 more