Alirocumab in Patients With Acute Myocardial Infarction

This research will study the effects of early initiation of alirocumab in addition to high
intensity statin therapy in patients who have previously been treated with high intensity
statins with poor response, who present with a type I (spontaneous) acute NSTEMI. Patients
will be dosed with drug or placebo once during the first day of their hospital admission.
Blood samples will be collected at baseline, 3 days and 14 days after randomization for
biomarker testing. Particular attention will be paid to additional LDL lowering effects, as
well as the effects on PCSK9 levels and inflammatory biomarkers. Safety and tolerability will
be monitored with complete blood count + differential and complete metabolic panels at each
study visit.

Inclusion Criteria:

1. Acute type I (spontaneous) NSTEMI defined as chest pain (or equivalent) with an onset
of symptoms within 12 hours of presentation, a duration of >15 minutes, and elevated
cardiac troponin I levels, with or without electrocardiographic changes [with the
exclusion of ST elevation];

2. On medical therapy with high intensity statin prior to admission (either atorvastatin
40-80 mg or rosuvastatin 20-40 mg) as documented by hospital or pharmacy records and
with known LDL cholesterol ≥70 mg/dL within the prior 12 months.

Exclusion Criteria:

1. Age <21 years of age

2. Inability to give informed consent

3. Previous, current or planned treatment with a PCSK9 inhibitor

4. Known history of loss of function of PCSK9 (genetic mutation or sequence variation)

5. Patient with homozygous familial hypercholesterolemia (clinically or by previous
genotyping)

6. Recent (<14 days) or active use of immunosuppressive drugs (including but not limited
to high-dose corticosteroids [>1mg/kg of prednisone equivalent], Tumor Necrosis
Factor-α blockers, cyclosporine) not including non-steroidal antinflammatory drugs or
corticosteroids used for IV dye allergy or corticosteroids used as replacement therapy
for pituitary/adrenal disease with a stable regimen for at least 6 weeks prior to
randomization (note: topical, intra-articular, nasal, inhaled, and ophthalmic steroid
therapies are not considered "systemic" and are allowed);

7. Chronic auto-immune or auto-inflammatory disease (including but not limited to
rheumatoid arthritis, systemic lupus erythematosus);

8. History of cancer within the past 5 years, except for adequately treated basal cell
skin cancer, squamous cell skin cancer, or in situ cervical cancer;

9. Known chronic hepatitis B or C infection (excluding patients with a positive antibody
who were successfully treated or who have demonstrated no viral load);

10. Known human immunodeficiency virus infection.

11. Use of fibrates other than fenofibrate within 6 weeks of the screening visit.

12. Uncontrolled hypothyroidism. Note: patients on thyroid replacement therapy can be
included if the dosage of thyroxin has been stable for at least 12 weeks prior to
screening.

13. Known history of a hemorrhagic stroke.

14. Has been previously treated with at least 1 dose of alirocumab or any other anti-PCSK9
monoclonal antibody in other clinical studies.

15. Conditions/situations such as:

1. Any clinically significant abnormality identified at the time of screening that
in the judgment of the investigator or any sub-investigator would preclude safe
completion of the study or constrain assessment of endpoints, such as major
systemic diseases or patients with short life expectancy.

2. Patients considered by the investigator or any sub-investigator to be
inappropriate for this study for any reason:

i. Those patients deemed unable to meet specific protocol requirements, such as
scheduled visits.

ii. Those patients the investigator deems unable to administer or tolerate long-term
injections.

c. Investigator or any sub-investigator, pharmacist, study coordinator, other study
staff, or relative thereof directly involved in the conduct of the protocol.

d. Presence of any other conditions (geographic or social), actual or anticipated,
that the investigator feels would restrict or limit the patient's participation for
the duration of the study.

16. Thyroid-stimulating hormone (TSH) < lower limit of normal (LLN) or > upper limit of
normal (ULN); if TSH is abnormal due to controlled hypothyroidism (patient is on a
stable dose of thyroid replacement therapy), the patient may be enrolled into the
study;

17. Exclusion Criteria Related to the Active Comparator and/or Mandatory Background
Therapies: All contraindications to the background therapies or warnings/precautions
of use (when appropriate) as displayed in the respective national product labeling.

18. Exclusion Criteria Related to the Current Knowledge of Alirocumab

1. Known hypersensitivity to monoclonal antibody therapeutics

2. Pregnant or breastfeeding women

19. Women of childbearing potential who are not protected by highly effective method(s) of
birth control throughout the entire duration of study treatment and for 10 weeks after
the last dose of study drug and/or who are unwilling or unable to be tested for
pregnancy.

20. Men capable of impregnating women who are not protected by highly effective method(s)
of birth control and/or who are unwilling to use an effective contraceptive method
throughout the entire duration of study treatment and for 10 weeks after the last dose
of study drug.