A Randomized, Double-blind Controlled Study Comparing LCZ696 to Medical Therapy for Comorbidities in HFpEF Patients

Inclusion Criteria:

- Left ventricular ejection fraction (LVEF) >40% by echo within 6 months prior to study
entry or during the screening epoch

- Symptom(s) of heart failure (HF) requiring treatment with diuretics (including loop,
or thiazide diuretics, or mineralocorticoid antagonist [MRAs]) for at least 30 days
prior to study entry

- NYHA class II-IV

- Structural heart disease (left atrial enlargement or left ventricular hypertrophy)
documented by echocardiogram.

- NT-proBNP > 220 pg/mL for patients with no atrial fibrillation/atrial flutter (AF) or
>600 pg/mL for patients with AF

- KCCQ clinical summary score < 75

- Patients on ACEi or ARB therapy must have a history of HTN

Exclusion Criteria:

- Any prior measurement of LVEF ≤ 40%, under stable conditions

- Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within
3 months , or urgent percutaneous coronary intervention (PCI) within 3 months or an
elective PCI within 30 days prior to study entry

- Any clinical event within the 6 months prior to Visit 1 that could have reduced the
LVEF (eg MI, coronary artery bypass graft [CABG]), unless an echo measurement was
performed after the event confirming the LVEF to be >40%

- Current (within 30 days from Visit 1) acute decompensated HF requiring therapy.

- Current (within 30 days from Visit 1) use of renin inhibitor(s), dual RAS blockade or
LCZ696

- History of hypersensitivity to LCZ696 or its components

- Patients with a known history of angioedema

- Walk distance primarily limited by non-cardiac comorbid conditions at study entry

- Alternative reason for shortness of breath such as: significant pulmonary disease or
severe COPD, hemoglobin (Hgb) <10 g/dL males and < 9.5 g/dL females, or body mass
index (BMI) > 40 kg/m^2.

- Systolic blood pressure (SBP) ≥ 180 mmHg at study entry, or SBP >150 mmHg and <180
mmHg at study entry unless the patient is receiving 3 or more antihypertensive drugs,
or SBP < 110 mmHg at study entry.

- Patients with HbA1c > 7.5% not treated for diabetes

- Patients with prior major organ transplant or intent to transplant (ie on transplant
list)

- eGFR < 30 ml/min/1.73 m^2 as measured by MDRD at screening

- Serum potassium > 5.2 mmol /L (or equivalent plasma potassium value) at study entry

- History or presence of any other disease with a life expectancy of < 3 years

- Pregnant or nursing women or women of child-bearing potential unless they are using
highly effective methods of contraception

Other protocol-defined inclusion/exclusion criteria may apply.