• Aucun résultat trouvé

Spironolactone for Heart Failure with Preserved Ejection Fraction

N/A
N/A
Protected

Academic year: 2022

Partager "Spironolactone for Heart Failure with Preserved Ejection Fraction"

Copied!
3
0
0

Texte intégral

(1)

20/5/2014 Spironolactone for Heart Failure with Preserved Ejection Fraction — NEJM

http://www.nejm.org/doi/full/10.1056/NEJMoa1313731 1/3

Access this article:

Or purchase this article - $15

Print Subscriber? Activate your online access now.

Learn how NEJM.org uses cookies at the Cookie Information page.

Welcome Guest Renew, Subscribe or Create Account Sign In

HOME ARTICLES & MULTIMEDIA ISSUES SPECIALTIES & TOPICS FOR AUTHORS CME Keyw ord, Title, Author, or Citation AdvancedSearch

Share:

Free Preview PRINT E-MAIL DOWNLOAD CITATION PERMISSIONS

BACKGROUND

Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction.

METHODS

In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure.

RESULTS

With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95%

confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis.

This article is available to subscribers.

Sign in now if you're a subscriber.

ORIGINA L A RT ICLE

Spironolactone for Heart Failure with Preserved Ejection Fraction

Bertram Pitt, M.D., Marc A. Pfeffer, M.D., Ph.D., Susan F. Assmann, Ph.D., Robin Boineau, M.D., Inder S. Anand, M.D., Brian Claggett, Ph.D., Nadine Clausell, M.D., Ph.D., Akshay S. Desai, M.D., M.P.H., Rafael Diaz, M.D., Jerome L. Fleg, M.D., Ivan Gordeev, M.D., Ph.D., Brian Harty, M.A., John F. Heitner, M.D., Christopher T. Kenw ood, M.S., Eldrin F. Lew is, M.D., M.P.H., Eileen O'Meara, M.D., Jeffrey L. Probstfield, M.D., Tamaz Shaburishvili, M.D., Ph.D., Sanjiv J. Shah, M.D., Scott D.

Solomon, M.D., Nancy K. Sw eitzer, M.D., Ph.D., Song Yang, Ph.D., and Sonja M. McKinlay, Ph.D. for the TOPCAT Investigators

N Engl J Med 2014; 370:1383-1392 April 10, 2014 DOI: 10.1056/NEJMoa1313731

MEDIA IN THIS ARTICLE FIGURE 1

Kaplan–Meier Plot of Time to the First Confirmed Primary- Outcome Event.

FIGURE 2

Kaplan–Meier Plots of Tw o Components of the Primary Outcome.

ARTICLE ACTIVITY 3 articles have cited this article

(2)

20/5/2014 Spironolactone for Heart Failure with Preserved Ejection Fraction — NEJM

http://www.nejm.org/doi/full/10.1056/NEJMoa1313731 2/3

CONCLUSIONS

In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number,

NCT00094302.)

The content of this article does not necessarily represent the view s of the National Heart, Lung, and Blood Institute or of the Department of Health and Human Services.

Supported by a contract from the National Heart, Lung, and Blood Institute, National Institutes of Health (HHSN268200425207C).

Dr. Pitt reports receiving consulting fees from and holding stock and stock options in AuraSense Therapeutics, receiving consulting fees from and holding stock options in Relypsa and BG Medicine, receiving consulting fees from Pfizer, Bayer, AstraZeneca, Amorcyte, Mesoblast, Takeda Pharmaceutical, and Gambro, receiving fees for serving on data and safety monitoring boards from Novartis and Johnson & Johnson, receiving fees for serving on a clinical-events committee from Juventas Therapeutics, receiving grant support from Forest Laboratories, and holding a pending patent related to site-specific delivery of eplerenone to the myocardium (14/175,733). Dr. Pfeffer reports receiving consulting fees and grant support from Amgen, consulting fees from Aastrom Biosciences, Abbott Vascular, Cerenis Therapeutics, Concert Pharmaceuticals, FibroGen, GlaxoSmithKline, Medtronic, Merck, Roche, Servier, and Teva Pharmaceuticals, and grant support from Celladon, Novartis, and Sanofi-Aventis and being a coinventor on patents related to the use of inhibitors of the renin–angiotensin system in selected survivors of myocardial infarction, w hich are licensed to Novartis and Boehringer Ingelheim (5,972,990 and 5,977,160). Dr. Desai reports receiving consulting fees from Novartis, Boston Scientific, Reata Pharmaceuticals, CardioMEMS, 5AM Ventures, Intel, and Relypsa, travel support from Amgen, and tonometry devices from AtCor Medical for use in an ancillary trial and providing expert testimony for Coverys on behalf of the defendant in a malpractice action regarding failure to diagnose heart failure. Dr. Lew is reports receiving grant support from Novartis, Amgen, and Sanofi-Aventis. Dr. O'Meara reports receiving consulting fees, lecture fees, and grant support from Servier, consulting fees and lecture fees from Pfizer, and consulting fees from Novartis. Dr. Shah reports receiving consulting fees from Novartis and Bayer and grant support from Gilead. Dr. Solomon reports receiving consulting fees and grant support from Novartis and consulting fees from Bayer.

No other potential conflict of interest relevant to this article w as reported.

Disclosure forms provided by the authors are available w ith the full text of this article at NEJM.org.

Drs. Pitt, Pfeffer, and McKinlay contributed equally to this article.

This article w as updated on April 10, 2014, at NEJM.org.

SOURCE INFORMATION

From the University of Michigan School of Medicine, Ann Arbor (B.P.); the Cardiovascular Division, Brigham and Women's Hospital, Boston (M.A.P., B.C., A.S.D., E.F.L., S.D.S.); New England Research Institutes, Watertow n, MA (S.F.A., B.H., C.T.K., S.M.M.); National Heart, Lung, and Blood Institute, Bethesda, MD (R.B., J.L.F., S.Y.); Veterans Affairs Medical Center and University of Minnesota, Minneapolis (I.S.A.); Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil (N.C.);

Estudios Clinicos Latinoamerica, Rosario, Argentina (R.D.); Pirogov Russian National Research Medical University, Moscow (I.G.); New York Methodist Hospital, Brooklyn (J.F.H.); Montreal Heart Institute, Montreal (E.O.); University of Washington Medical Center, Seattle (J.L.P.); Diagnostic Services Clinic, Tbilisi, Georgia (T.S.);

Northw estern University, Chicago (S.J.S.); and the University of Wisconsin, Madison (N.K.S.).

Address reprint requests to Dr. Pfeffer at the Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115, or at

mpfeffer@rics.bw h.harvard.edu.

A complete list of investigators and committees in the Treatment of Preserved Cardiac Function Heart Failure w ith an Aldosterone Antagonist (TOPCAT) trial is provided in the Supplementary Appendix, available at NEJM.org.

Access this article: Subscribe to NEJM | Purchase this article

CONTENT:Home Current Issue Articles Issue Index Specialties & Topics Multimedia & Images Archive 1812-1989 INFORMATION FOR:Authors Review ers Subscribers Institutions Media Advertisers

SERVICES:Subscribe Renew Pay Bill Activate Subscription Create or Manage Account Alerts RSS & Podcasts Submit a Manuscript Mobile RESOURCES:Physician Jobs Reprints Permissions Medical Meetings Conventions FAQs NEJM Know ledge+ NEJM Journal Watch Help Contact Us

(3)

20/5/2014 Spironolactone for Heart Failure with Preserved Ejection Fraction — NEJM

http://www.nejm.org/doi/full/10.1056/NEJMoa1313731 3/3

Copyright © 2014 Massachusetts Medical Society. All rights reserved.

NEJM:About Product Information Editors & Publishers 200th Anniversary Terms of Use Privacy Policy Copyright Advertising Policies NEJM Group CME:Weekly CME Program Brow se Weekly Exams Your CME Activity Purchase Exams Review CME Program

Follow us

Références

Documents relatifs

/ La version de cette publication peut être l’une des suivantes : la version prépublication de l’auteur, la version acceptée du manuscrit ou la version de l’éditeur. For

Optimal breeding strategy for mouse mutant strains Gael Grannec, Marika Nosten-Bertrand.. To cite

Our hypothesis is that these chromosome intermingling regions serve as mechanical hotspots that harbor cell- type specific gene clusters and integrate micro-environmental signals

ACICS gadgets are pairs of Indirect Call Sites (ICS) and target functions that enable Remote Code Ex- ecution (RCE) while respecting a CFG enforced using fine-grained CFI.

[r]

Currently, two papers [387,389] have proposed practical guides to address such research questions using mediation analysis through multiple pathways (i.e. potential

En effet, lorsque les affects en viennent à se confondre avec une menace d’ef- fraction ou de déformation de soi, leur effacement semble parfois s’imposer comme façon de