The Aliskiren Trial to Minimize OutcomeS in Patients with HEart failure trial (ATMOSPHERE): revised statistical analysis plan and baseline characteristics.
OBJECTIVE
To: (i) describe the baseline characteristics of patients in ATMOSPHERE and the changes in the planned analysis of ATMOSPHERE resulting from the mandated discontinuation of study treatment in patients with diabetes; (ii) compare the baseline characteristics of patients in ATMOSPHERE with those in the Prospective comparison of Angiotensin Receptor neprilysin inhibitors with Angiotensin converting enzyme inhibitors to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF); and (iii) compare the characteristics of patients with and without diabetes at baseline in ATMOSPHERE.


RESULTS
A total of 7063 patients were randomized into ATMOSPHERE April 2009-April 2014 at 755 sites in 43 countries. Their average age was 63 years and 78% were men. ATMOSPHERE patients were generally similar to those in PARADIGM-HF although fewer had diabetes, renal dysfunction, and were treated with a mineralocorticoid receptor antagonist. In ATMOSPHERE, patients with diabetes differed in numerous ways from those without. Patients with diabetes were older and had worse heart failure status but a similar left ventricular ejection fraction (mean 28%); they had a higher body mass index and more co-morbidity, especially hypertension and coronary heart disease. Mean estimated glomerular filtration rate was slightly lower in those with diabetes compared with those without.


CONCLUSIONS
ATMOSPHERE will determine whether patients with HF and reduced ejection fraction (particularly those without diabetes) benefit from the addition of a direct renin inhibitor to standard background therapy, including an angiotensin-converting enzyme inhibitor, beta-blocker, and a mineralocorticoid receptor antagonist. ATMOSPHERE will also determine whether aliskiren alone is superior to, or at least non-inferior to, enalapril.
Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia.
Henry
H
Krum
British Heart Foundation Research Centre, University of Glasgow, 126 University Place, Glasgow, 126 University Place, Scotland, UK.
John J V
JJ
McMurray
Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH, USA.
William T
WT
Abraham
Stavanger University Hospital, Stavanger, Norway and Institute of Internal Medicine, University of Bergen, Bergen, Norway.
Kenneth
K
Dickstein
Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
Lars
L
Køber
Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Akshay S
AS
Desai
Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Scott D
SD
Solomon
Novartis Pharma AG, Basel, Switzerland.
Yanntong
Y
Chiang
Novartis Pharma AG, Basel, Switzerland.
Claudio
C
Gimpelewicz
Novartis Pharma AG, Basel, Switzerland.
Bernard
B
Reimund
Novartis Pharma AG, Basel, Switzerland.
M Atif
MA
Ali
Novartis Pharma AG, Basel, Switzerland.
Georgia
G
Tarnesby
University of California, San Francisco, CA, USA.
Barry M
BM
Massie
D000577:Amides / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D002317:Cardiovascular Agents / Q000008:administration & dosage; D003920:Diabetes Mellitus; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage; D005260:Female; D005650:Fumarates / Q000008:administration & dosage*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013318:Stroke Volume; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy; D000092502:Renin Inhibitors
D000577:Amides; D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents; D004656:Enalapril; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren
Aliskiren; Characteristics; Heart failure