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Dementia-related adverse effects in the prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF).

Session Poster session 1 Saturday 08:30 -17:30

Speaker John McMurray

Congress : Heart Failure 2015

  • Topic : heart failure
  • Sub-topic : Chronic Heart Failure
  • Session type : Poster Session
  • FP Number : P242

Authors : J Cannon (Glasgow,GB), S Boytsov (Moscow,RU), M Senni (Bergamo,IT), J L Rouleau (Montreal,CA), S D Solomon (Boston,US), K Swedberg (Gothenburg,SE), M Zile (Charleston,US), F Chen (Hanover,US), J J V Mcmurray (Glasgow,GB), M Packer (Dallas,US)

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Authors:
J Cannon1 , S Boytsov2 , M Senni3 , J L Rouleau4 , S D Solomon5 , K Swedberg6 , M Zile7 , F Chen8 , J J V Mcmurray1 , M Packer9 , 1University of Glasgow, BHF Cardiovascular Research Centre - Glasgow - United Kingdom , 2National Research Center for Preventive Medicine - Moscow - Russian Federation , 3Ospedale Papa Giovanni XXIII - Bergamo - Italy , 4University of Montreal - Montreal - Canada , 5Brigham and Women's Hospital - Boston - United States of America , 6University of Gothenburg, Department of Molecular and Clinical Medicine - Gothenburg - Sweden , 7Medical University of South Carolina - Charleston - United States of America , 8Novartis Pharmaceutical Corporation - Hanover - United States of America , 9University of Texas Southwestern Medical School - Dallas - United States of America ,

On behalf: PARADIGM-HF Committees and Investigators

Citation:
European Journal of Heart Failure Abstracts Supplement ( 2015 ) 17 ( Supplement 1 ), 49

Background: Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction, as shown in PARADIGM-HF which compared the angiotensin receptor neprilysin inhibitor (ARNI) LCZ696 (sacubitril-valsartan) to enalapril. As neprilysin is also one of many enzymes clearing amyloid-β peptides from the brain, there is theoretical concern about the long-term effects of LCZ696 on cognition. Therefore, we examined dementia-related adverse effects in PARADIGM-HF.

Methods: Patients with NYHA class II-IV heart failure (HF), a LVEF ≤40% and a mildly elevated BNP/NT proBNP were randomized to LCZ696 200mg bid or enalapril 10mg bid in a 1:1 ratio. We searched adverse event reports (AERs) coded using the Medical Dictionary for Regulatory Activities (MedRA) using Standardized MedRA Queries (SMQs) with "broad" and "narrow" preferred terms (PTs) related to cognition, memory, dementia-like and related events.

Results: 8399 patients aged 18-96 yrs were randomized and followed for a median of 2.25 yrs (up to 4.3 yrs). The narrow SMQ search identified 27 relevant AERs: 15 (0.35%) on enalapril and 12 (0.29%) on LCZ696 (HR 0.79, 0.37-1.70). The numbers using the broad search were: 83 (1.96%) and 86 (2.05%), respectively, HR 1.03 (0.76, 1.39). The most common PTs in each treatment group are shown in the Table.

Conclusion: We found no evidence that LCZ696, compared with enalapril, increased dementia-related adverse events in PARADIGM-HF.

Broad SMQ Dementia

LCZ696 n (%)

Enalapril n (%)

Confusional state

12 (0.29)

18 (0.43)

Somnolence

11 (0.26)

9 (0.21)

Amnesia

10 (0.24)

7 (0.17)

Delirium

10 (0.24)

8 (0.19)

Agitation

7 (0.17)

3 (0.07)

Memory impairment

6 (0.14)

6 (0.14)

Dementia

6 (0.14)

10 (0.24)

Narrow SMQ Dementia

Dementia

6 (0.14)

10 (0.24)

Dementia Alzheimer's type

2 (0.05)

2 (0.05)

Vascular dementia

2 (0.05)

1 (0.02)

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It is now only available year-round to HFA Silver & Gold Members, Fellows of the ESC and Young combined Members



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