Author + information
- Received August 20, 2018
- Revision received September 21, 2018
- Accepted September 25, 2018
- Published online January 7, 2019.
- Pooja Dewan, MBChBa,
- Rasmus Rørth, MDa,b,
- Pardeep S. Jhund, MBChB, PhDa,
- Li Shen, MBChB, PhDa,
- Valeria Raparelli, MD, PhDc,d,
- Mark C. Petrie, MBChBa,
- William T. Abraham, MDe,
- Akshay S. Desai, MDf,
- Kenneth Dickstein, MD, PhDg,
- Lars Køber, MD, DMScb,
- Ulrik M. Mogensen, MD, PhDa,b,
- Milton Packer, MDh,
- Jean L. Rouleau, MDi,
- Scott D. Solomon, MDf,
- Karl Swedberg, MD, PhDj,k,
- Michael R. Zile, MDl and
- John J.V. McMurray, MDa,∗ (, )@TheBHF@UofGlasgow
- aBHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
- bDepartment of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
- cCenter for Outcomes Research and Evaluation, Research Institute, McGill University Health Centre, Montreal, Quebec, Canada
- dDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy
- eDivision of Cardiovascular Medicine, Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio
- fCardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts
- gDepartment of Cardiology, Stavanger University Hospital, University of Bergen, Stavanger, Norway
- hBaylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas
- iInstitut de Cardiologie de Montréal, Université de Montréal, Montréal, Quebec, Canada
- jDepartment of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
- kNational Heart and Lung Institute, Imperial College London, London, United Kingdom
- lDivision of Cardiology, Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina
- ↵∗Address for correspondence:
Dr. John J.V. McMurray, British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, United Kingdom.
Background Heart failure (HF) trials initiated in the last century highlighted many differences between men and women. Of particular concern was undertreatment of women compared with men, but much has changed during the past 20 years.
Objectives This study sought to identify these changes, which may give a new perspective on the management of, and outcomes in, women with HF.
Methods The study analyzed 12,058 men and 3,357 women enrolled in 2 large HF with reduced ejection fraction (HFrEF) trials with near identical inclusion and exclusion criteria and the same principal outcomes. Outcomes were adjusted for other prognostic variables including N-terminal pro–B-type natriuretic peptide.
Results Women were older and more often obese than men were, had slightly higher systolic blood pressure and heart rate, and were less likely to have most comorbidities, except hypertension. Women had more symptoms and signs (e.g., pedal edema 23.4% vs 19.9%; p < 0.0001) and worse quality of life—median Kansas City Cardiomyopathy Questionnaire Clinical Summary Score 71.3 (interquartile range: 53.4 to 86.5) versus 81.3 (interquartile range: 65.1 to 92.7; p < 0.0001)—despite similar left ventricular ejection fraction and N-terminal pro–B-type natriuretic peptide. However, women had lower mortality (adjusted hazard ratio: 0.68; 95% confidence interval: 0.62 to 0.74; p < 0.001) and risk of HF hospitalization (hazard ratio: 0.80; 95% confidence interval: 0.72 to 0.89; p < 0.001). Diuretics and anticoagulants were underutilized in women. Device therapy was underused in both men and women, but more so in women (e.g., defibrillator 8.6% vs. 16.6%; p < 0.0001).
Conclusions Although women with HFrEF live longer than men, their additional years of life are of poorer quality, with greater self-reported psychological and physical disability. The explanation for this different sex-related experience of HFrEF is unknown as is whether physicians recognize it. Women continue to receive suboptimal treatment, compared with men, with no obvious explanation for this shortfall.
The ATMOSPHERE and PARADIGM-HF trials were funded by Novartis and Mr. Petrie and Drs. Jhund, Abraham, Desai, Dickstein, Køber, Packer, Rouleau, Solomon, Swedberg, Zile, and McMurray or their institutions were paid by Novartis for their participation in one or both of these trials. Dr. Jhund has received speaker and advisory board membership fees from Novartis; and advisory board membership fees from Boehringer Ingelheim and Vifor Pharma. Dr. Desai has served as a consultant for Novartis, Abbott, AstraZeneca, DalCor, Relypsa, Regeneron, Signature Medical, Boston Scientific, and Boehringer Ingelheim. Dr. Packer has served as a consultant for Actavis, Amgen, Boehringer Ingelheim, AstraZeneca, Cardiorentis, Daiichi-Sankyo, Gilead, Relypsa, Sanofi, Takeda, and Synthetic Biologics. Dr. Rouleau has served as a consultant for Novartis and AstraZeneca. Dr. Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bristol-Myers Squibb, Celladon, Gilead, GlaxoSmithKline, Ionis, LoneStar Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and has served as a consultant for Akros, Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Corvia, Gilead, GlaxoSmithKline, Ironwood, Merck, Novartis, Pfizer, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, Abiomed, and Janssen. Dr. Swedberg has served as a consultant for AstraZeneca, Novartis, and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received August 20, 2018.
- Revision received September 21, 2018.
- Accepted September 25, 2018.
- 2019 The Authors