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Original research article
Individual participant data analysis of two trials on aldosterone blockade in myocardial infarction
  1. Farzin Beygui1,
  2. Eric Van Belle2,
  3. Patrick Ecollan3,
  4. Jacques Machecourt4,
  5. Christian W Hamm5,
  6. Estaeban Lopez De Sa6,
  7. Marcus Flather7,
  8. Freek W A Verheugt8,
  9. Eric Vicaut9,
  10. Faiez Zannad10,
  11. Bertram Pitt11,
  12. Gilles Montalescot12
  1. 1ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Caen, EA4650 Normandie Université, Caen, Basse-Normandie, France
  2. 2INSERM U1011 and Cardiology, Institut Coeur Poumon, CHRU de Lille, Lille, France
  3. 3SAMU, ACTION Study Group, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France
  4. 4Service de Cardiologie, Centre Hospitalier Universitaire de Grenoble, Grenoble, Rhône-Alpes, France
  5. 5Kerckhoff Clinic, Bad Nauheim, Germany
  6. 6La Paz University Hospital, Madrid, Spain
  7. 7Cardiology, University of East Anglia and Norfolk and Norwich University Hospital, Norwich, UK
  8. 8Hospital Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
  9. 9ACTION Study Group, Unite de Recherche Clinique, Hôpital Lariboisière, Paris, France
  10. 10Inserm CIC 1433 and Cardiology, Centre Hospitalier Universitaire de Nancy, Vandœuvre-lès-Nancy, France
  11. 11University of Michigan Hospital, Ann Arbor, Michigan, USA
  12. 12Cardiology, Sorbonne Université-Paris 6, ACTION Study Group, Institut de Cardiologie (AP-HP), Centre Hospitalier Universitaire Pitié-Salpêtriėre, INSERM UMRS 1166, Paris, France
  1. Correspondence to Professor Farzin Beygui, ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Caen, EA4650 Normandie Université, Caen 14000, France; beygui-f{at}chu-caen.fr

Abstract

Background Two recent randomised trials studied the benefit of mineralocorticoid receptor antagonists (MRAs) in ST-segment elevation myocardial infarction (STEMI) irrespective or in absence of heart failure. The studies were both undersized to assess hard clinical endpoints. A pooled analysis was preplanned by the steering committees.

Methods We conducted a prespecified meta-analysis of patient-level data of patients with STEMI recruited in two multicentre superiority trials, randomised within 72 hours after symptom onset. Patients were allocated (1:1) to two MRA regimens: (1) an intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) versus standard therapy or (2) oral eplerenone (25–50 mg) versus placebo. The primary and key secondary outcomes, all-cause death and the composite of all-cause death or resuscitated sudden death, respectively, were assessed in the intention-to-treat population using a Cox model stratified on the study identifier.

Results Patients were randomly assigned to receive (n=1118) or not the MRA regimen (n=1123). After a median follow-up time of 188 days, the primary and secondary outcomes occurred in 5 (0.4%) and 17 (1.5%) patients (adjusted HR (adjHR) 0.31, 95% CI 0.11 to 0.86, p=0.03) and 6 (0.5%) and 22 (2%) patients (adjHR 0.26, 95% CI 0.10 to 0.65, p=0.004) in the MRA and control groups, respectively. There were also trends towards lower rates of cardiovascular death (p=0.06) and ventricular fibrillation (p=0.08) in the MRA group.

Conclusion Our analysis suggests that compared with standard therapy, MRA regimens are associated with a reduction of death and death or resuscitated sudden death in STEMI.

  • acute myocardial infarction

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Footnotes

  • Contributors Study concept and design: FB, EV and GM. Analysis and interpretation of data: FB, EV. Drafting of the manuscript: FB, GM. Critical revision of the manuscript for important intellectual content: EVB, PE, JM, CWH, ELDS, MF, FWAV, FZ and BP. Statistical analysis: FB, EV. Study supervision/guarantor: GM, BP. The first and last author had full access to all the data, prepared the first draft of the manuscript. The manuscript was approved by all coauthors, who made the decision to submit the manuscript for publication and assumed responsibility for data accuracy.

  • Funding The ALBATROSS trial was led by members of the non-profit academic research organisation ACTION, based at Pitié-Salpêtrière Hospital, Paris, France (www.action-coeur.org). The study was sponsored by the Assistance Publique-Hôpitaux de Paris (AP-HP) and exclusively funded by public grants from the French Ministry of Health and the Foundation of the Institute of Cardiometabolism And Nutrition (ICAN). The REMINDER trial was funded by Pfizer. The REMINDER steering committee and Pfizer provided the data and gave consent for the pooled analysis. The funding organisations had no involvement in the analysis of the results or writing of the present manuscript. No specific funding was used to support this work.

  • Competing interests FB has received institutional grants and/or lecture or consultancy honoraria from AstraZeneca, Medtronic, Boston Scientific, Biosensor and Acist. CWH has received speaker fees from Pfizer. GM declares his competing interests on http://action-coeur.org/declarations-dinterets/.

  • Patient consent Not required.

  • Ethics approval REMINDER trial was approved by each participating centre’s ethics committee; ALBATROSS trial was approved by the French National Institutional Ethical Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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