Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

Ulrik M Mogensen; Jianjian Gong; Pardeep S Jhund; Li Shen; Lars Køber; Akshay S Desai; Martin P Lefkowitz; Milton Packer; Jean L Rouleau; Scott D Solomon; Brian L Claggett; Karl Swedberg; Michael R Zile; Guenther Mueller-Velten; John J V McMurray

doi:10.1002/ejhf.1139

Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

Ulrik M Mogensen, Jianjian Gong, Pardeep S Jhund, Li Shen, Lars Køber, Akshay S Desai, Martin P Lefkowitz, Milton Packer, Jean L Rouleau, Scott D Solomon, Brian L Claggett, Karl Swedberg, Michael R Zile, Guenther Mueller-Velten, John J V McMurray

Department of Clinical Medicine

33 Citations (Scopus)

25 Downloads (Pure)

Abstract

Aims: Recurrent hospitalizations are a major part of the disease burden in heart failure (HF), but conventional analyses consider only the first event. We compared the effect of sacubitril/valsartan vs. enalapril on recurrent events, incorporating all HF hospitalizations and cardiovascular (CV) deaths in PARADIGM-HF, using a variety of statistical approaches advocated for this type of analysis. Methods and results: In PARADIGM-HF, a total of 8399 patients were randomized and followed for a median of 27 months. We applied various recurrent event analyses, including a negative binomial model, the Wei, Lin and Weissfeld (WLW), and Lin, Wei, Ying and Yang (LWYY) methods, and a joint frailty model, all adjusted for treatment and region. Among a total of 3181 primary endpoint events (including 1251 CV deaths) during the trial, only 2031 (63.8%) were first events (836 CV deaths). Among a total of 1195 patients with at least one HF hospitalization, 410 (34%) had at least one further HF hospitalization. Sacubitril/valsartan compared with enalapril reduced the risk of recurrent HF hospitalization using the negative binomial model [rate ratio (RR) 0.77, 95% confidence interval (CI) 0.67–0.89], the WLW method [hazard ratio (HR) 0.79, 95% CI 0.71–0.89], the LWYY method (RR 0.78, 95% CI 0.68–0.90), and the joint frailty model (HR 0.75, 95% CI 0.66–0.86) (all P < 0.001). The effect of sacubitril/valsartan vs. enalapril on recurrent HF hospitalizations/CV death was similar. Conclusions: In PARADIGM-HF, approximately one third of patients with a primary endpoint (time-to-first) experienced a further event. Compared with enalapril, sacubitril/valsartan reduced both first and recurrent events. The treatment effect size was similar, regardless of the statistical approach applied.

Original language	English
Journal	European Journal of Heart Failure
Volume	20
Issue number	4
Pages (from-to)	760-768
Number of pages	9
ISSN	1388-9842
DOIs	https://doi.org/10.1002/ejhf.1139
Publication status	Published - Apr 2018

Keywords

Aged
Aminobutyrates/administration & dosage
Angiotensin Receptor Antagonists/administration & dosage
Angiotensin-Converting Enzyme Inhibitors/administration & dosage
Dose-Response Relationship, Drug
Enalapril/administration & dosage
Europe/epidemiology
Female
Heart Failure/drug therapy
Humans
Male
Middle Aged
Morbidity/trends
Prospective Studies
Recurrence
Stroke Volume/physiology
Survival Rate/trends
Tetrazoles/administration & dosage
United States/epidemiology

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10.1002/ejhf.1139Licence: CC BY-NC

Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF)Final published version, 720 KBLicence: CC BY-NC

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Mogensen, U. M., Gong, J., Jhund, P. S., Shen, L., Køber, L., Desai, A. S., Lefkowitz, M. P., Packer, M., Rouleau, J. L., Solomon, S. D., Claggett, B. L., Swedberg, K., Zile, M. R., Mueller-Velten, G., & McMurray, J. J. V. (2018). Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). European Journal of Heart Failure, 20(4), 760-768. https://doi.org/10.1002/ejhf.1139

Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). / Mogensen, Ulrik M; Gong, Jianjian; Jhund, Pardeep S et al.

In: European Journal of Heart Failure, Vol. 20, No. 4, 04.2018, p. 760-768.

Research output: Contribution to journal › Journal article › Research › peer-review

Mogensen, UM, Gong, J, Jhund, PS, Shen, L, Køber, L, Desai, AS, Lefkowitz, MP, Packer, M, Rouleau, JL, Solomon, SD, Claggett, BL, Swedberg, K, Zile, MR, Mueller-Velten, G & McMurray, JJV 2018, 'Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)', European Journal of Heart Failure, vol. 20, no. 4, pp. 760-768. https://doi.org/10.1002/ejhf.1139

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title = "Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)",

abstract = "Aims: Recurrent hospitalizations are a major part of the disease burden in heart failure (HF), but conventional analyses consider only the first event. We compared the effect of sacubitril/valsartan vs. enalapril on recurrent events, incorporating all HF hospitalizations and cardiovascular (CV) deaths in PARADIGM-HF, using a variety of statistical approaches advocated for this type of analysis. Methods and results: In PARADIGM-HF, a total of 8399 patients were randomized and followed for a median of 27 months. We applied various recurrent event analyses, including a negative binomial model, the Wei, Lin and Weissfeld (WLW), and Lin, Wei, Ying and Yang (LWYY) methods, and a joint frailty model, all adjusted for treatment and region. Among a total of 3181 primary endpoint events (including 1251 CV deaths) during the trial, only 2031 (63.8%) were first events (836 CV deaths). Among a total of 1195 patients with at least one HF hospitalization, 410 (34%) had at least one further HF hospitalization. Sacubitril/valsartan compared with enalapril reduced the risk of recurrent HF hospitalization using the negative binomial model [rate ratio (RR) 0.77, 95% confidence interval (CI) 0.67–0.89], the WLW method [hazard ratio (HR) 0.79, 95% CI 0.71–0.89], the LWYY method (RR 0.78, 95% CI 0.68–0.90), and the joint frailty model (HR 0.75, 95% CI 0.66–0.86) (all P < 0.001). The effect of sacubitril/valsartan vs. enalapril on recurrent HF hospitalizations/CV death was similar. Conclusions: In PARADIGM-HF, approximately one third of patients with a primary endpoint (time-to-first) experienced a further event. Compared with enalapril, sacubitril/valsartan reduced both first and recurrent events. The treatment effect size was similar, regardless of the statistical approach applied.",

keywords = "Aged, Aminobutyrates/administration & dosage, Angiotensin Receptor Antagonists/administration & dosage, Angiotensin-Converting Enzyme Inhibitors/administration & dosage, Dose-Response Relationship, Drug, Enalapril/administration & dosage, Europe/epidemiology, Female, Heart Failure/drug therapy, Humans, Male, Middle Aged, Morbidity/trends, Prospective Studies, Recurrence, Stroke Volume/physiology, Survival Rate/trends, Tetrazoles/administration & dosage, United States/epidemiology",

author = "Mogensen, {Ulrik M} and Jianjian Gong and Jhund, {Pardeep S} and Li Shen and Lars K{\o}ber and Desai, {Akshay S} and Lefkowitz, {Martin P} and Milton Packer and Rouleau, {Jean L} and Solomon, {Scott D} and Claggett, {Brian L} and Karl Swedberg and Zile, {Michael R} and Guenther Mueller-Velten and McMurray, {John J V}",

note = "{\textcopyright} 2018 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.",

year = "2018",

month = apr,

doi = "10.1002/ejhf.1139",

language = "English",

volume = "20",

pages = "760--768",

journal = "European Journal of Heart Failure, Supplement",

issn = "1567-4215",

publisher = "JohnWiley & Sons Ltd",

number = "4",

}

TY - JOUR

T1 - Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

AU - Mogensen, Ulrik M

AU - Gong, Jianjian

AU - Jhund, Pardeep S

AU - Shen, Li

AU - Køber, Lars

AU - Desai, Akshay S

AU - Lefkowitz, Martin P

AU - Packer, Milton

AU - Rouleau, Jean L

AU - Solomon, Scott D

AU - Claggett, Brian L

AU - Swedberg, Karl

AU - Zile, Michael R

AU - Mueller-Velten, Guenther

AU - McMurray, John J V

PY - 2018/4

Y1 - 2018/4

N2 - Aims: Recurrent hospitalizations are a major part of the disease burden in heart failure (HF), but conventional analyses consider only the first event. We compared the effect of sacubitril/valsartan vs. enalapril on recurrent events, incorporating all HF hospitalizations and cardiovascular (CV) deaths in PARADIGM-HF, using a variety of statistical approaches advocated for this type of analysis. Methods and results: In PARADIGM-HF, a total of 8399 patients were randomized and followed for a median of 27 months. We applied various recurrent event analyses, including a negative binomial model, the Wei, Lin and Weissfeld (WLW), and Lin, Wei, Ying and Yang (LWYY) methods, and a joint frailty model, all adjusted for treatment and region. Among a total of 3181 primary endpoint events (including 1251 CV deaths) during the trial, only 2031 (63.8%) were first events (836 CV deaths). Among a total of 1195 patients with at least one HF hospitalization, 410 (34%) had at least one further HF hospitalization. Sacubitril/valsartan compared with enalapril reduced the risk of recurrent HF hospitalization using the negative binomial model [rate ratio (RR) 0.77, 95% confidence interval (CI) 0.67–0.89], the WLW method [hazard ratio (HR) 0.79, 95% CI 0.71–0.89], the LWYY method (RR 0.78, 95% CI 0.68–0.90), and the joint frailty model (HR 0.75, 95% CI 0.66–0.86) (all P < 0.001). The effect of sacubitril/valsartan vs. enalapril on recurrent HF hospitalizations/CV death was similar. Conclusions: In PARADIGM-HF, approximately one third of patients with a primary endpoint (time-to-first) experienced a further event. Compared with enalapril, sacubitril/valsartan reduced both first and recurrent events. The treatment effect size was similar, regardless of the statistical approach applied.

AB - Aims: Recurrent hospitalizations are a major part of the disease burden in heart failure (HF), but conventional analyses consider only the first event. We compared the effect of sacubitril/valsartan vs. enalapril on recurrent events, incorporating all HF hospitalizations and cardiovascular (CV) deaths in PARADIGM-HF, using a variety of statistical approaches advocated for this type of analysis. Methods and results: In PARADIGM-HF, a total of 8399 patients were randomized and followed for a median of 27 months. We applied various recurrent event analyses, including a negative binomial model, the Wei, Lin and Weissfeld (WLW), and Lin, Wei, Ying and Yang (LWYY) methods, and a joint frailty model, all adjusted for treatment and region. Among a total of 3181 primary endpoint events (including 1251 CV deaths) during the trial, only 2031 (63.8%) were first events (836 CV deaths). Among a total of 1195 patients with at least one HF hospitalization, 410 (34%) had at least one further HF hospitalization. Sacubitril/valsartan compared with enalapril reduced the risk of recurrent HF hospitalization using the negative binomial model [rate ratio (RR) 0.77, 95% confidence interval (CI) 0.67–0.89], the WLW method [hazard ratio (HR) 0.79, 95% CI 0.71–0.89], the LWYY method (RR 0.78, 95% CI 0.68–0.90), and the joint frailty model (HR 0.75, 95% CI 0.66–0.86) (all P < 0.001). The effect of sacubitril/valsartan vs. enalapril on recurrent HF hospitalizations/CV death was similar. Conclusions: In PARADIGM-HF, approximately one third of patients with a primary endpoint (time-to-first) experienced a further event. Compared with enalapril, sacubitril/valsartan reduced both first and recurrent events. The treatment effect size was similar, regardless of the statistical approach applied.

KW - Aged

KW - Aminobutyrates/administration & dosage

KW - Angiotensin Receptor Antagonists/administration & dosage

KW - Angiotensin-Converting Enzyme Inhibitors/administration & dosage

KW - Dose-Response Relationship, Drug

KW - Enalapril/administration & dosage

KW - Europe/epidemiology

KW - Female

KW - Heart Failure/drug therapy

KW - Humans

KW - Male

KW - Middle Aged

KW - Morbidity/trends

KW - Prospective Studies

KW - Recurrence

KW - Stroke Volume/physiology

KW - Survival Rate/trends

KW - Tetrazoles/administration & dosage

KW - United States/epidemiology

U2 - 10.1002/ejhf.1139

DO - 10.1002/ejhf.1139

M3 - Journal article

C2 - 29431251

SN - 1567-4215

VL - 20

SP - 760

EP - 768

JO - European Journal of Heart Failure, Supplement

JF - European Journal of Heart Failure, Supplement

IS - 4

ER -

Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

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Keywords

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