Prospective ARNI vs ACE Inhibitor Trial to DetermIne Superiority in Reducing Heart Failure Events After MI

Inclusion Criteria:

1. Male or female patients ≥ 18 years of age.

2. Diagnosis of spontaneous AMI based on the universal MI definition* with randomization
to occur between 12 hours and 7 days after index event presentation. (*patients with
spontaneous MI event determined to be secondary to another medical condition such as
anemia, hypotension, or arrhythmia OR thought to be caused by coronary vasospasm with
document normal coronary arteries are not eligible; patients with clinical
presentation thought to be related to Takotsubo cardiomyopathy are also not eligible)

3. Evidence of LV systolic dysfunction and/or pulmonary congestion requiring intravenous
treatment associated with the index MI event defined as:

- LVEF ≤40% after index MI presentation and prior to randomization and/or

- Pulmonary congestion requiring intravenous treatment with diuretics,
vasodilators, vasopressors and/or inotropes, during the index hospitalization

4. At least one of the following 8 risk factors:

- Age ≥ 70 years

- eGFR <60 mL/min/1.73 m^2 based on MDRD formula at screening visit

- Type I or II diabetes mellitus

- Documented history of prior MI

- Atrial fibrillation as noted by ECG, associated with index MI

- LVEF <30% associated with index MI

- Worst Killip class III or IV associated with index MI requiring intravenous
treatment

- STEMI without reperfusion therapy within the first 24 hours after presentation

5. Hemodynamically stable defined as:

- SBP ≥ 100 mmHg at randomization for patients who received ACEi/ARB during the
last 24 hours prior to randomization

- SBP ≥ 110 mmHg at randomization for patients who did not receive ACEi/ARB during
the last 24 hours prior to randomization

- No IV treatment with diuretics, vasodilators, vasopressors and/or inotropes
during the 24 hours prior to randomization

Key Exclusion Criteria:

1. Known history of chronic HF prior to randomization

2. Cardiogenic shock within the last 24 hours prior to randomization

3. Persistent clinical HF at the time of randomization

4. Coronary artery bypass graft (CABG) performed or planned for index MI

5. Clinically significant right ventricular MI as index MI

6. Symptomatic hypotension at screening or randomization

7. Patients with a known history of angioedema

8. Stroke or transient ischemic attack within one month prior to randomization

9. Known or suspected bilateral renal artery stenosis

10. Clinically significant obstructive cardiomyopathy

11. Open-heart surgery performed within one month prior to randomization or planned
cardiac surgery w/in the 3 months prior to randomization

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

13. Serum potassium > 5.2 mmol /L (or equivalent plasma potassium value) at randomization

14. Known hepatic impairment (as evidenced by total bilirubin > 3.0 mg/dL or increased
ammonia levels, if performed), or history of cirrhosis with evidence of portal
hypertension such as esophageal varices

15. Previous use of LCZ696

16. History of malignancy of any organ system (other than localized basal cell carcinoma
of the skin) within the past 3 years with a life expectancy of less than 1year.

17. History of hypersensitivity to the study drugs or drugs of similar chemical classes or
known intolerance or contraindications to study drugs or drugs of similar chemical
classes including ACE inhibitors, ARB or NEP inhibitors

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