Methods of reducing the risk of cardiovascular events in a subject

• US 10,668,042 B2
• Filed: 04/22/2019
• Issued: 06/02/2020
• Est. Priority Date: 09/24/2018
• 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): Rao, Savitha M
• Application Number:
  US16/391,128
• Publication Number:
  US 20200093777A1
• Time in Patent Office: 407 Days
• 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 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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 disclosure provides methods reducing the risk of cardiovascular events in a subject on statin therapy by 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 one or more of:

myocardial infarction, stroke, cardiovascular death, unstable angina, coronary revascularization procedures and/or hospitalizations for unstable angina in a subject in need thereof, the method comprising administering daily to the subject 4 g of eicosapentaenoic acid ethyl ester (E-EPA) and a high intensity statin regimen, wherein the subject has elevated triglyceride levels and (1) established cardiovascular disease, or (2) diabetes and at least 2 additional risk factors for cardiovascular disease, wherein the high intensity statin regimen comprises about 40 mg to about 80 mg per day of atorvastatin or about 20 mg to about 40 mg per day of rosuvastatin.

2. The method of claim 1, wherein risk of occurrence of one or more components of a 3-point composite endpoint composed of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke is reduced in the subject.

3. The method of claim 2, wherein risk of occurrence of one or more components of the 3-point composite endpoint composed of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke is reduced by at least about 20% in the subject.

4. The method of claim 1, wherein risk of occurrence of one or more components of a 5-point composite endpoint composed of cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, or unstable angina requiring hospitalization is reduced in the subject.

5. The method of claim 4, wherein risk of occurrence of one or more components of the 5-point composite endpoint composed of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or unstable angina requiring hospitalization is reduced by at least about 20% in the subject.

6. The method of claim 1, wherein the subject is less than about 65 years of age.

7. The method of claim 1, wherein the subject has a high sensitivity reactive protein (hsCRP) level of 2 mg/L or less.

8. The method of claim 1, wherein the subject has a fasting baseline triglyceride level of at least about 200 mg/dL and a fasting baseline high density lipoprotein-C (HDL-C) level of about 35 mg/dL or less.

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

10. The method of claim 1, wherein the administering occurs for at least about 2 years.