| Participants |
Estimated enrolment: 520
Inclusion criteria:
Written informed consent including consent for APOE4 gene testing must be obtained before any assessment is performed Male or female patients aged ≥ 60 years of age. Chronic heart failure with current symptom(s) (NYHA class II‐IV) at Screening visit. -
LVEF > 40%
By any method using most recent assessment within 6 months prior to screening visit OR By an echocardiogram performed during the screening visit, if previous assessment is not available.
NT‐proBNP ≥ 125 pg/mL at Screening visit Patient with evidence of adequate functioning (e.g.: intellectual, motor, visual and auditory) to complete the study assessments and has elementary education or 6 years of sustained employment.
Exclusion criteria:
Current acute decompensated HF requiring augmented therapy with diuretics, vasodilators and/or inotropic drugs. Acute coronary syndrome (including myocardial infarction (MI)), cardiac surgery, other major cardiovascular (CV) surgery, or urgent percutaneous coronary intervention (PCI), carotid surgery or carotid angioplasty, history of stroke or transient ischemic attack within the 3 months prior to Screening visit or an elective PCI within 30 days prior to Screening visit. Patients with history of hereditary or idiopathic angioedema or angioedema related to previous angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapies. Patients who require treatment with 2 or more of the following: an ACEi, an ARB or a renin inhibitor. Patients with one of the following:
a. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) formula at screening visit, or b. eGFR <25 mL/min/1.73m2 at Visit 103 or at end of run‐in / randomization visit, or c. eGFR reduction >35% (compared to Visit 1) at Visit 103 or Visit 199/201
MMSE score <24 at Screening visit Patients with a clinical diagnosis of Alzheimer’s disease or other dementia syndromes or any indication for or current treatment with cholinesterase inhibitors and/or another prescription Alzheimer’s Disease (AD) treatment (e.g., memantine). Any history of medical or neurological condition likely to affect the participant’s cognition (e.g., clinically significant brain trauma with loss of consciousness > 3 minutes within 6 months prior to screening, Huntington’s disease, Parkinson’s disease, Lyme’s disease, syphilis, HIV dementia, uncontrolled seizure disorder) or clinically significant abnormalities in thyroid function tests, Vitamin B12 or folate deficiencyrequiring treatment at screening. (Patients who are adequately treated may be included at investigator discretion). Inability to perform cognitive battery or other study evaluations based on significant motor (e.g. hemiplegia, muscular‐skeletal injury) or sensory (blindness, decreased or uncorrected visual or auditory acuity) skill. Score “yes” on item 4 or item 5 of the Suicidal Ideation section of the Columbia suicidality severity rating scale (C‐SSRS), if this ideation occurred in the past 6 months, or “yes” on any item of the Suicidal Behavior section, except for the “Non‐Suicidal Self‐Injurious Behavior” (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years. Clinically significant cerebral pathology, for example large cerebral aneurysm, space occupying lesion etc. that may impact cognition as assessed by MRI central reader. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. History or presence of any other disease with a life expectancy of <3 years Women of child bearing potential defined as all women physiologically capable of becoming pregnant.
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