Incidence and Outcomes of Pneumonia in Patients With Heart Failure

Li Shen, Pardeep S. Jhund, Inder S. Anand, Ankeet S. Bhatt, Akshay S. Desai, Aldo P. Maggioni, Felipe A. Martinez, Marc A. Pfeffer, Adel R. Rizkala, Jean L. Rouleau, Karl Swedberg, Muthiah Vaduganathan, Orly Vardeny, Dirk J. van Veldhuisen, Faiez Zannad, Michael R. Zile, Milton Packer, Scott D. Solomon, John J.V. McMurray

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Background: The incidence of pneumonia and subsequent outcomes has not been compared in patients with heart failure and reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Objectives: This study aimed to examine the rate and impact of pneumonia in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) and PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in Heart Failure with Preserved Ejection Fraction) trials. Methods: The authors analyzed the incidence of investigator-reported pneumonia and the rates of HF hospitalization, cardiovascular death, and all-cause death before and after the occurrence of pneumonia, and estimated risk after the first occurrence of pneumonia in unadjusted and adjusted analyses (the latter including N-terminal pro–B-type natriuretic peptide). Results: In PARADIGM-HF, 528 patients (6.3%) developed pneumonia after randomization, giving an incidence rate of 29 (95% CI: 27 to 32) per 1,000 patient-years. In PARAGON-HF, 510 patients (10.6%) developed pneumonia, giving an incidence rate of 39 (95% CI: 36 to 42) per 1,000 patient-years. The subsequent risk of all trial outcomes was elevated after the occurrence of pneumonia. In PARADIGM-HF, the adjusted hazard ratio (HR) for the risk of death from any cause was 4.34 (95% CI: 3.73 to 5.05). The corresponding adjusted HR in PARAGON-HF was 3.76 (95% CI: 3.09 to 4.58). Conclusions: The incidence of pneumonia was high in patients with HF, especially HFpEF, at around 3 times the expected rate. A first episode of pneumonia was associated with 4-fold higher mortality. (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF], NCT01035255; Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] With ARB [Angiotensin Receptor Blocker] Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF], NCT01920711)

Original languageEnglish (US)
Pages (from-to)1961-1973
Number of pages13
JournalJournal of the American College of Cardiology
Issue number16
StatePublished - Apr 27 2021

Bibliographical note

Funding Information:
The PARADIGM-HF and PARAGON-HF trials were funded by Novartis. Dr. McMurray is supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217). Drs Jhund, Anand, Bhatt, Desai, Maggioni, Martinez, Pfeffer, Rizkala, Rouleau, Swedberg, Vaduganathan, Vardeny, van Veldhuisen, Zannad, Zile, Packer, Solomon, and McMurray or their institutions have received funding from Novartis.

Publisher Copyright:
© 2021 The Authors


  • heart failure
  • incidence
  • pneumonia
  • risk
  • vaccination


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