Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: Insights from PARADIGM-HF

Pardeep S. Jhund, Michael Fu, Edmundo Bayram, Chen Huan Chen, Marta Negrusz-Kawecka, Arvo Rosenthal, Akshay S. Desai, Martin P. Lefkowitz, Adel R. Rizkala, Jean L. Rouleau, Victor C. Shi, Scott D. Solomon, Karl Swedberg, Michael R. Zile, John J V McMurray, Milton Packer

Research output: Contribution to journalArticle

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Abstract

Background The age at which heart failure develops varies widely between countries and drug tolerance and outcomes also vary by age.We have examined the efficacy and safety of LCZ696 according to age in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Methods In PARADIGM-HF, 8399 patients aged 18.96 years and in New York Heart Association functional class II.IV with an LVEF .40% were randomized to either enalapril or LCZ696.We examined the pre-specified efficacy and safety outcomes according to age category (years): ,55 (n . 1624), 55.64 (n . 2655), 65.74 (n . 2557), and .75 (n . 1563). Findings The rate (per 100 patient-years) of the primary outcome of cardiovascular (CV) death or heart failure hospitalization (HFH) increased from 13.4 to 14.8 across the age categories. The LCZ696:enalapril hazard ratio (HR) was ,1.0 in all categories (P for interaction between age category and treatment . 0.94) with an overall HR of 0.80 (0.73, 0.87), P , 0.001. The findings for HFH were similar for CV and all-cause mortality and the age category by treatment interactions were not significant. The pre-specified safety outcomes of hypotension, renal impairment and hyperkalaemia increased in both treatment groups with age, although the differences between treatment (more hypotension but less renal impairment and hyperkalaemia with LCZ696) were consistent across age categories. Interpretation LCZ696 was more beneficial than enalapril across the spectrum of age in PARADIGM-HF with a favourable benefit. risk profile in all age groups.

Original languageEnglish (US)
Pages (from-to)2576-2584
Number of pages9
JournalEuropean Heart Journal
Volume36
Issue number38
DOIs
StatePublished - Oct 7 2015

Fingerprint

Enalapril
Safety
Heart Failure
Hyperkalemia
Hypotension
Hospitalization
Age Groups
Drug Tolerance
Kidney
Neprilysin
Angiotensin Receptors
Mortality
Therapeutics
Angiotensin-Converting Enzyme Inhibitors
LCZ 696
Morbidity

Keywords

  • Age
  • Angiotensin
  • Heart failure
  • Neprilysin
  • Receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Jhund, P. S., Fu, M., Bayram, E., Chen, C. H., Negrusz-Kawecka, M., Rosenthal, A., ... Packer, M. (2015). Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: Insights from PARADIGM-HF. European Heart Journal, 36(38), 2576-2584. https://doi.org/10.1093/eurheartj/ehv330

Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age : Insights from PARADIGM-HF. / Jhund, Pardeep S.; Fu, Michael; Bayram, Edmundo; Chen, Chen Huan; Negrusz-Kawecka, Marta; Rosenthal, Arvo; Desai, Akshay S.; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean L.; Shi, Victor C.; Solomon, Scott D.; Swedberg, Karl; Zile, Michael R.; McMurray, John J V; Packer, Milton.

In: European Heart Journal, Vol. 36, No. 38, 07.10.2015, p. 2576-2584.

Research output: Contribution to journalArticle

Jhund, PS, Fu, M, Bayram, E, Chen, CH, Negrusz-Kawecka, M, Rosenthal, A, Desai, AS, Lefkowitz, MP, Rizkala, AR, Rouleau, JL, Shi, VC, Solomon, SD, Swedberg, K, Zile, MR, McMurray, JJV & Packer, M 2015, 'Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: Insights from PARADIGM-HF', European Heart Journal, vol. 36, no. 38, pp. 2576-2584. https://doi.org/10.1093/eurheartj/ehv330
Jhund PS, Fu M, Bayram E, Chen CH, Negrusz-Kawecka M, Rosenthal A et al. Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: Insights from PARADIGM-HF. European Heart Journal. 2015 Oct 7;36(38):2576-2584. https://doi.org/10.1093/eurheartj/ehv330
Jhund, Pardeep S. ; Fu, Michael ; Bayram, Edmundo ; Chen, Chen Huan ; Negrusz-Kawecka, Marta ; Rosenthal, Arvo ; Desai, Akshay S. ; Lefkowitz, Martin P. ; Rizkala, Adel R. ; Rouleau, Jean L. ; Shi, Victor C. ; Solomon, Scott D. ; Swedberg, Karl ; Zile, Michael R. ; McMurray, John J V ; Packer, Milton. / Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age : Insights from PARADIGM-HF. In: European Heart Journal. 2015 ; Vol. 36, No. 38. pp. 2576-2584.
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AU - Chen, Chen Huan

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AU - Lefkowitz, Martin P.

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