Methods of reducing the risk of a cardiovascular event in a subject at risk for cardiovascular disease

• US 10,383,840 B2
• Filed: 02/27/2019
• Issued: 08/20/2019
• Est. Priority Date: 06/29/2012
• Status: Active Grant

• Current Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Original Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Inventors: Soni, Paresh
• Primary Examiner(s): Vajda, Kristin A
• Application Number:
  US16/287,157
• Publication Number:
  US 20190192472A1
• Time in Patent Office: 174 Days
• Field of Search: 514549
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: A61K 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

In various embodiments, the present invention provides methods of reducing the risk of a cardiovascular event in a subject on statin therapy and, in particular, a method of reducing the risk of a cardiovascular event in a subject on statin therapy having a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL, and administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of eicosapentaenoic acid ethyl ester or a derivative thereof.

Claims

1. A method of reducing risk of a cardiovascular event in a subject with at least one risk factor for cardiovascular disease who is at LDL-C goal, the method comprising administering to said subject a pharmaceutical composition comprising about 4 g of icosapent ethyl per day for a period effective to reduce risk of the cardiovascular event in the subject.

2. The method of claim 1, wherein the cardiovascular event is one or more of:

cardiovascular death, myocardial infarction, stroke, coronary revascularization, and unstable angina.

3. The method of claim 1, wherein the administration affects a relative risk reduction of said cardiovascular event of at least about 25%.

4. The method of claim 1, wherein the subject has a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL.

5. The method of claim 1, wherein the LDL-C goal is an LDL-C level of about 40 mg/dL to about 100 mg/dL.

6. The method of claim 1, wherein the subject has established cardiovascular disease.

7. The method of claim 1, wherein the subject has diabetes.

8. The method of claim 1, wherein the at least one risk factor for cardiovascular disease is selected from the following risk factors:

(a) the subject is a male of at least 55 years of age or a female of at least 65 years of age, (b) the subject smokes cigarettes or has stopped smoking cigarettes within three months before administration of the pharmaceutical composition, (c) the subject has a blood pressure of at least 140 mmHg systolic or at least 90 mmHg diastolic, (d) the subject is receiving antihypertension medication, (e) the subject is a male with HDL-cholesterol level 40 mg/dL or less or is a female with HDL-cholesterol level 50 mg/dL or less, (0 the subject has a hs-CRP level of greater than 3 mg/L, (g) the subject has a creatine clearance between 30 mL/min and 60 mL/min, (h) the subject has non-proliferative retinopathy, (i) the subject has pre-proliferative retinopathy, (j) the subject has proliferative retinopathy, (k) the subject has maculopathy, (l) the subject has advanced diabetic eye disease or a history of photocoagulation, (m) the subject has micro- or macro-albuminuria, and (n) the subject has a asymptomatic ankle-brachial index of less than 0.9.

9. The method of claim 1, wherein the pharmaceutical composition is administered to the subject in 1 to 8 dosage units per day.

10. The method of claim 1, wherein the icosapent ethyl comprises at least about 90 wt. % of all omega-3 fatty acids in the pharmaceutical composition.

11. The method of claim 1, wherein the icosapent ethyl comprises at least about 96 wt. % of all omega-3 fatty acids in the pharmaceutical composition.

12. The method of claim 1 further comprising a step of measuring the subject'"'"'s baseline lipid profile prior to administering the pharmaceutical composition to the subject.

13. The method of claim 12, wherein the subject has one or more of:

a baseline non-HDL-C value of about 200 mg/dL to about 300 mg/dL;

a baseline total cholesterol value of about 250 mg/dL to about 300 mg/dL;

a baseline VLDL-C value of about 140 mg/dL to about 200 mg/dL;

a baseline HDL-C value of about 10 to about 30 mg/dL; and

/or a baseline LDL-C value of about 40 to about 100 mg/dL.

14. The method of claim 1, wherein the subject:

(a) has not been administered 200 mg or more per day of niacin and/or fibrates for at least 28 days before administration of the pharmaceutical composition;

(b) has not been administered omega-3 fatty acid prescription for a period of time beginning 28 days prior to administration of the pharmaceutical composition;

or (c) has not ingested dietary supplements comprising omega-3 fatty acids for a period of time beginning 28 days prior to administration of the pharmaceutical composition.

15. The method of claim 1, wherein said period ends about 6 months, about 1 year, about 2 years, about 3 years, about 4 years, about 5 years, or more than about 5 years after the first administration of the pharmaceutical composition.

16. The method of claim 1, wherein the subject is administered about 4 g of the pharmaceutical composition per day for at least about 3 years.