Efficacy and Safety of Sacubitril/Valsartan Compared to Valsartan on Cognitive Function in Patients With Chronic Heart Failure and Preserved Ejection Fraction - PERSPECTIVE

Aug 26, 2022
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, FACC, MBA
Date Presented:
08/26/2022
Date Published:
08/26/2022
Date Updated:
08/26/2022
Original Posted Date:
08/26/2022
References

Contribution To Literature:

The PERSPECTIVE trial failed to show improvement in cognitive function with sacubitril/valsartan.

Description:

The goal of the trial was to evaluate sacubitril/valsartan compared with valsartan among symptomatic heart failure patients.

Study Design

  • Randomization
  • Parallel

Eligible individuals were randomized to sacubitril/valsartan 97/103 mg (n = 295) versus valsartan 160 mg (n = 297).

  • Total number of enrollees: 592
  • Duration of follow-up: 3 years
  • Mean patient age: 72.3 years
  • Percentage female: 45%
  • Percentage with diabetes: 41%

Inclusion criteria:

  • Symptomatic heart failure
  • Age ≥60 years
  • Left ventricular ejection fraction: >40%
  • N-terminal pro–B-type natriuretic peptide >200 pg/mL and/or heart failure hospitalization within prior 12 months
  • Consent to APOE4 gene testing

Exclusion criteria:

  • Serum potassium >5.4 mmol/L
  • Estimated glomerular filtration rate <25 ml/min/1.73 m2
  • Systolic blood pressure (SBP) ≥180 mm Hg
  • Symptomatic hypotension or SBP <100 mm Hg
  • Contraindication to brain magnetic resonance imaging (MRI)
  • Dementia
  • Mini-Mental State Examination (MMSE) score <24 at screening visit
  • Suicidal ideation
  • Other relevant neurological disease/inability to undertake cognitive function tests
  • Significant cerebral vascular disease on screening brain MRI

Principal Findings:

The primary outcome, global cognition composite score: difference at 36 months was -0.0180 (p = 0.74).

The secondary outcome, amyloid positron emission tomography (PET) imaging (standardized uptake value ratio): difference at 36 months was -0.0292 (p = 0.058).

Interpretation:

Among patients with symptomatic heart failure, sacubitril/valsartan was not beneficial at improving cognitive function. Beta-amyloid brain deposition was nonsignificantly reduced with sacubitril/valsartan. The effect of sacubitril/valsartan on cognitive function remains inconclusive.

References:

Presented by Dr. John J.V. McMurray at the European Society of Cardiology Congress (ESC 2022), Barcelona, Spain, August 26, 2022.

Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Computed Tomography, Magnetic Resonance Imaging, Nuclear Imaging

Keywords: ESC Congress, ESC22, Amyloid, Cognition, Diagnostic Imaging, Geriatrics, Heart Failure, Magnetic Resonance Imaging, Natriuretic Peptide, Brain, Positron-Emission Tomography, Stroke Volume, Valsartan, Ventricular Function, Left


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