Study of Efficacy and Safety of LCZ696 in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed.
• Outpatients with a diagnosis of CHF NYHA class II-IV and reduced ejection fraction:
• LVEF ≤ 35% at Visit 1 (any local measurement, made within the past 6 months usingechocardiography, MUGA, CT scanning, MRI or ventricular angiography is alsoacceptable, provided no subsequent measurement above 35%)
• NT-proBNP ≥ 600 pg/ml at Visit 1 OR NT-proBNP ≥ 400 pg/ml at Visit 1 and ahospitalization for HF within the last 12 months (according to central laboratorymeasurements)
• Patients must be on an ACEI or an ARB at a stable dose for at least 4 weeks beforeVisit 1.
• Patients must be treated with a β-blocker, unless contraindicated or not tolerated, ata stable dose for at least 4 weeks prior to Visit 1 (reason should be documented ifpatients reported contraindications or intolerance).
• An aldosterone antagonist should also be considered in all patients, taking account ofrenal function, serum potassium and tolerability. If given, the dose of aldosteroneantagonist should be optimized according to guideline recommendations and patienttolerability, and should be stable for at least 4 weeks prior to Visit 1. Otherevidence-based therapy for HF should also be considered e.g. cardiac resynchronizationtherapy and an implantable cardioverter-defibrillator in selected patients, asrecommended by guidelines.

Exclusion Criteria:

• History of hypersensitivity to any of the study drugs or to drugs of similar chemicalclasses, ACEIs, ARBs, NEP inhibitors as well as known or suspected contraindicationsto the study drugs.
• Previous documented history of intolerance to ACEIs or ARBs.
• Known history of angioedema.
• Requirement of treatment with both ACEIs and ARBs.
• Current acute decompensated HF (exacerbation of chronic HF manifested by signs andsymptoms that may require intravenous therapy).
• Symptomatic hypotension and/or a SBP < 100 mmHg at screening or < 95 mmHg at the endof run-in.
• Estimated GFR < 30 mL/min/1.73 m2 as measured by the Japanese formula at screening, orthe end of run-in or > 35% decline in eGFR between screening and end of run-in (according to local measurements).
• Serum potassium > 5.2 mmol/L (mEq/L) at screening or > 5.4 mmol/L (mEq/L) at the endof run-in (according to local measurements).
• Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or othermajor CV surgery, percutaneous coronary intervention (PCI) or carotid angioplastywithin the 3 months prior to Visit 1.
• Documented untreated ventricular arrhythmia with syncopal episodes within the 3 monthsprior to Visit 1.
• Symptomatic bradycardia or second (except asymptomatic Wenckebach block) or thirddegree heart block without a pacemaker.
• Presence of hemodynamically significant mitral and/or aortic valve disease, exceptmitral regurgitation secondary to left ventricular dilatation.
• Presence of other hemodynamically significant obstructive lesions of left ventricularoutflow tract, including aortic and sub-aortic stenosis.
• Presence of bilateral renal artery stenosis.