LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction

• Change in log-scale in BNP, MR-proBNP, cGMP [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: No ]
• Change in echocardiography parameters [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: No ]
• Change in the overall summary score and individual domain score of the Kansas City Cardiomyopathy questionnaire [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: No ]
• Change in clinical composite score (NYHA and global patient assessment score) time frame [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: Yes ]
• class indicators of signs and symptoms of heart failure at each visit [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: No ]

• Change in log-scale in BNP, MR-proBNP, cGMP [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Change in echocardiography parameters [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Class indicators of signs and symptoms of heart failure at each visit [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Change in the overall summary score and individual domain score of the Kansas City Cardiomyopathy questionnaire [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Change in clinical composite score (NYHA and global patient assessment score) time frame [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

The study will assess the effects of 36 weeks of treatment with LCZ696 compared to valsartan on N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in patients with chronic heart failure and preserved left-ventricular ejection fraction.

• Drug: LCZ696
  LCZ696 50 mg titrated to 100 mg and 200 mg
• Drug: Valsartan
  Valsartan 40 mg titrated to 80 mg and 160 mg

• Experimental: LCZ696
  LCZ696 50 mg titrated to 100 mg and 200 mg
  Intervention: Drug: LCZ696
• Active Comparator: Valsartan
  Valsartan 40 mg titrated to 80 mg and 160 mg
  Intervention: Drug: Valsartan

Inclusion Criteria:

• Patients with documented stable chronic heart failure (NYHA II-IV):

  • LVEF ≥ 45% (local measurement, assessed by echocardiography, MUGA, CT scan, MRI or ventricular angiography)
  • the ejection fraction must have been obtained within 6 months prior to randomization or after any MI or other event that would affect ejection fraction.
• Plasma NT-proBNP > 500 pg/ml at Visit 1.
• Patients with documented stable chronic heart failure (NYHA II-IV).
• Patients receiving ACE inhibitors (ACEi), an angiotensin receptor blockers (ARB) and/or a beta blockers must be on a stable dose of these medications stable for the 1 month period prior to Visit 1.
• Patients must be on diuretic therapy prior to Visit 1 (flexible dosing is permitted).
• Patients with a controlled systolic BP, defined as a target systolic BP less than 140 mm Hg; participants with BP up to and including 160 mm Hg are eligible for enrollment if they are on three or more medications to control BP at randomization (Visit 2).

• Patients with at least one of the following symptoms at the time of screening (Visit 1):

  • Dyspnea on exertion
  • Orthopnea
  • Paroxysmal nocturnal dyspnea
  • Peripheral edema
• Patients must have an eGFR ≥ 30 ml/min/1.73 m2 at Visit 1 (calculated by the Modification of Diet in Renal Disease formula).
• Patients with a potassium ≤5.2 mmol/l at Visit 1.

Exclusion Criteria:

• Patients with a prior LVEF reading <45%, at any time.
• Patients who require treatment with both an ACE inhibitor and an ARB.
• Isolated right heart failure due to pulmonary disease.
• Dyspnea and/or edema from non-cardiac causes, such as lung disease, anemia, or severe obesity.
• Presence of hemodynamically significant mitral and /or aortic valve disease.
• Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis.
• Presence of hypertrophic obstructive cardiomyopathy.
• Other protocol-defined inclusion/exclusion criteria may apply