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. 2020 Apr 1;5(4):432-441.
doi: 10.1001/jamacardio.2019.5850.

Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure Registry to Predict Mortality and Morbidity in Chronic Heart Failure

Joanne Simpson  1 , Pardeep S Jhund  1 , Lars H Lund  2 , Sandosh Padmanabhan  1 , Brian L Claggett  3 , Li Shen  1 , Mark C Petrie  1 , William T Abraham  4 , Akshay S Desai  3 , Kenneth Dickstein  5 , Lars Køber  6 , Milton Packer  7 , Jean L Rouleau  8 , Guenther Mueller-Velten  9 , Scott D Solomon  3 , Karl Swedberg  10   11 , Michael R Zile  12   13 , John J V McMurray  1
Affiliations

Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure Registry to Predict Mortality and Morbidity in Chronic Heart Failure

Joanne Simpson et al. JAMA Cardiol. .

Erratum in

  • Error in Abstract.
    [No authors listed] [No authors listed] JAMA Cardiol. 2020 Apr 1;5(4):488. doi: 10.1001/jamacardio.2020.0451. JAMA Cardiol. 2020. PMID: 32159732 Free PMC article. No abstract available.

Abstract

Importance: Accurate prediction of risk of death or hospitalizations in patients with heart failure (HF) may allow physicians to explore how more accurate decisions regarding appropriateness and timing of disease-modifying treatments, advanced therapies, or the need for end-of-life care can be made.

Objective: To develop and validate a prognostic model for patients with HF.

Design, setting, and participants: Multivariable analyses were performed in a stepwise fashion. Harrell C statistic was used to assess the discriminative ability. The derivation cohort was Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF) participants. The models were validated using the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure Trial (ATMOSPHERE) study and in the Swedish Heart Failure Registry (SwedeHF). A total of 8399 participants enrolled in PARADIGM-HF. Data were analyzed between June 2016 and June 2018.

Main outcomes and measures: Cardiovascular death, all-cause mortality, and the composite of cardiovascular death or HF hospitalization at both 1 and 2 years.

Results: Complete baseline clinical data were available for 8011 patients in PARADIGM-HF. The mean (SD) age of participants was 64 (11.4) years, 78.2% were men (n = 6567 of 8399), and 70.6% were New York Heart Association class II (n = 5919 of 8399). During a mean follow-up of 27 months, 1546 patients died, and 2031 had a cardiovascular death or HF hospitalization. The common variables were: male sex, race/ethnicity (black or Asian), region (Central Europe or Latin America), HF duration of more than 5 years, New York Heart Association class III/ IV, left ventricular ejection fraction, diabetes mellitus, β-blocker use at baseline, and allocation to sacubitril/valsartan. Ranked by χ2, N-terminal pro brain natriuretic peptide was the single most powerful independent predictor of each outcome. The C statistic at 1 and 2 years was 0.74 (95% CI, 0.71-0.76) and 0.71 (95% CI, 0.70-0.73) for the primary composite end point, 0.73 (95% CI, 0.71-0.75) and 0.71 (95% CI, 0.69-0.73) for cardiovascular death, and 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.67-0.74) for all-cause death, respectively. When validated in ATMOSPHERE, the C statistic at 1 and 2 years was 0.71 (95% CI, 0.69-0.72) and 0.70 (95% CI, 0.68-0.71) for the primary composite end point, 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.69-0.72) for cardiovascular death, and 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.68-0.72) for all-cause death, respectively. An online calculator was created to allow calculation of an individual's risk (http://www.predict-hf.com).

Conclusions and relevance: Predictive models performed well and were developed and externally validated in large cohorts of geographically representative patients, comprehensively characterized with clinical and laboratory data including natriuretic peptides, who were receiving contemporary evidence-based treatment.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Jhund reported personal fees from Novartis during the conduct of the study; grants from Boehringer Ingelheim, other support from AstraZeneca, and personal fees from Cytokinetics outside the submitted work. Dr Lund reported grants and personal fees from Novartis, AstraZeneca, Boehringer Ingelheim, and Vifor Pharma; personal fees from Bayer, Sanofi, Merck, Abbott, Medscape, and Pharmacosmos; and grants from Boston Scientific outside the submitted work. Dr Petrie reported grants and personal fees from Astra Zeneca and Boehringer Ingelheim and personal fees from Novo Nordisk, Novartis, Alnylam, Cardiorentis, and Resverlogix outside the submitted work. Dr Abraham reported personal fees from Novartis during the conduct of the study and personal fees from Abbott, Boehringer Ingelheim, Edwards Lifesciences, Respicardia, and Sensible Medical outside the submitted work. Dr Desai reported grants from Novartis during the conduct of the study; grants and personal fees from Abbott, Alnylam, Biofourmis, and AstraZeneca; and personal fees from Amgen, Boston Scientific, Boehringer Ingelheim, DalCor Pharma, Novartis, Relypsa, and Regeneron outside the submitted work. Dr Køber reported other support from Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, during the conduct of the study and personal fees from speakers honorarium from Novartis and AstraZeneca outside the submitted work. Dr Packer reported personal fees from AbbVie, Akcea, Amgen, AstraZeneca, Actavis, Boehringer Ingelheim, Cardiorentis, Sankyo, Johnson & Johnson, Novo Nordisk, Pfizer, Sanofi, Synthetic Biologics, and Theravance outside the submitted work. Dr Rouleau reported personal fees from Novartis during the conduct of the study and from AstraZeneca outside the submitted work. Dr Solomon reported grants from Novartis during the conduct of the study; grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and personal fees from Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, BMS, Cardior, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GSK, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, and Tenaya outside the submitted work. Dr Swedberg reported personal fees from Novartis during the conduct of the study and from AstraZeneca, Pfizer, and Novartis outside the submitted work. Dr Zile reported grants and personal fees from Novartis during the conduct of the study. Dr McMurray reported other support from Novartis during the conduct of the study and from Novartis, Amgen, GSK, Theracos, DalCor Pharmaceuticals, AstraZeneca, BMS, and Cardurion. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Observed and Predicted Risk in Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF) at 1 Year for Primary Composite End Point (A), Cardiovascular Death (B), and All-Cause Mortality for Patients Categorized by Quintile of Risk Scores (C)
A, Predicted vs observed risk of primary composite end point at 1 year. B, Predicted vs observed risk of cardiovascular death at 1 year. C, Predicted vs observed risk of all-cause mortality at 1 year.
Figure 2.
Figure 2.. Observed and Predicted Risk in Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF) at 2 Years for Primary Composite End Point (A), Cardiovascular Death (B), and All-Cause Mortality for Patients Categorized by Quintile of Risk Score (C)
A, Predicted vs observed risk of primary composite end point at 2 years. B, Predicted vs observed risk of cardiovascular death at 2 years. C. Predicted vs observed risk of all-cause mortality at 2 years.
See this image and copyright information in PMC

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