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Randomized Controlled Trial
. 2015 Oct 7;36(38):2576-84.
doi: 10.1093/eurheartj/ehv330. Epub 2015 Jul 31.

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

Pardeep S Jhund  1 , Michael Fu  2 , Edmundo Bayram  3 , Chen-Huan Chen  4 , Marta Negrusz-Kawecka  5 , Arvo Rosenthal  6 , Akshay S Desai  7 , Martin P Lefkowitz  8 , Adel R Rizkala  8 , Jean L Rouleau  9 , Victor C Shi  8 , Scott D Solomon  7 , Karl Swedberg  10 , Michael R Zile  11 , John J V McMurray  12 , Milton Packer  13 ; PARADIGM-HF Investigators and Committees
Affiliations
Randomized Controlled Trial

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

Pardeep S Jhund et al. Eur Heart J. .

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.

Trial registration: ClinicalTrials.gov NCT01035255.

Keywords: Age; Angiotensin; Heart failure; Neprilysin; Receptors.

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Figures

Figure 1
Figure 1
Clinical outcomes of cardiovascular death or heart failure hospitalization, cardiovascular death, heart failure hospitalization, and all-cause mortality by age category and treatment group. Rates are expressed as a rate per 100 patient-years of treatment (error bars are 95% confidence intervals).
Figure 2
Figure 2
LCZ696 to enalapril hazard ratio (line) and 95% confidence intervals (shaded area) for clinical outcomes [cardiovascular death or heart failure hospitalization (A), cardiovascular death (B), heart failure hospitalization (C), and all-cause mortality (D)] according to age. A hazard ratio of 1.0 is indicated by the solid horizontal line. A hazard ratio of <1.0 favours LCZ696.
Figure 3
Figure 3
Proportion of patients with a five-point or greater fall (deterioration) in Kansas City Cardiomyopathy Questionnaire at 8 months by age category and treatment.
See this image and copyright information in PMC

References

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