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
Incidence, Predictors, and Outcomes Related to Hypo- and Hyperkalemia in Patients With Severe Heart Failure Treated With a Mineralocorticoid Receptor Antagonist
Orly Vardeny,Brian Claggett,Inder S. Anand,Patrick Rossignol,Akshay S. Desai,Faiez Zannad,Bertram Pitt,Scott D. Solomon +7 more
TL;DR: In this paper, the authors assessed incidence and predictors of hyperkalemia (potassium ≥ 5.5 mmol/L) and hypokalemia, and the relationship to outcomes in 1663 patients with class III or IV heart failure and left ventricular ejection fraction <35% randomized to treatment with spironolactone 25 mg or placebo in the Randomized Aldactone Evaluation Study (RALES) trial.
Journal ArticleDOI
Effects of renin-angiotensin system inhibition end-organ protection: Can we do better?
TL;DR: Clinical data supporting the use of RAS inhibitors (ACE inhibitors and ARBs) as monotherapy or combination therapy based on the known role of the RAS in BP regulation and the vascular response to injury is presented, and the implications of the data for future treatment are considered.
Journal ArticleDOI
Identifying Heart Failure Patients at High Risk for Near-Term Cardiovascular Events With Serial Health Status Assessments
Mikhail Kosiborod,Gabriel E. Soto,Philip G. Jones,Harlan M. Krumholz,William S. Weintraub,Prakash Deedwania,John A. Spertus +6 more
TL;DR: In heart failure outpatients, serial health status assessments with the Kansas City Cardiomyopathy Questionnaire can identify high-risk patients and may prove useful in directing the frequency of follow-up and the intensity of treatment.
Journal ArticleDOI
A New Mode of Mineralocorticoid Receptor Antagonism by a Potent and Selective Nonsteroidal Molecule
Jérôme Fagart,Jérôme Fagart,Alexander Hillisch,Jessica Huyet,Jessica Huyet,Lars Bärfacker,Michel Fay,Michel Fay,Ulrich Pleiss,Elisabeth Pook,Stefan Schäfer,Marie-Edith Rafestin-Oblin,Marie-Edith Rafestin-Oblin,Peter Kolkhof +13 more
TL;DR: It is proposed that BR-4628 is a bulky antagonist that inactivates MR through a passive mechanism and represents the prototype of a new class of MR antagonists.
Journal ArticleDOI
30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development.
Peter Kolkhof,Lars Bärfacker +1 more
TL;DR: Novel non-steroidal MRAs such as apararenone, esaxerenone and finerenone are in late-stage clinical trials in patients with heart failure, chronic kidney disease, hypertension and liver disease and the history of the various generations of MRAs is reflected.
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