Methods of reducing the risk of a cardiovascular event in a subject on statin therapy
View Patent ↗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.
1. A method of reducing risk of a cardiovascular event in a subject on statin therapy with residual atherogenic dyslipidemia and clinically evident cardiovascular disease, the method comprising administering to the subject a pharmaceutical composition comprising about 4 g of eicosapentaenoic acid in triglyceride form per day for a period of at least about 2 years, wherein said administration reduces risk of cardiovascular death, risk of unstable angina and/or need for coronary revascularization.
2. The method of claim 1 , wherein the composition is administered to the subject in 1 to 4 dosage units per day.
3. The method of claim 1 , wherein the eicosapentaenoic acid in triglyceride form comprises at least about 96 wt. % of all omega-3 fatty acids in the pharmaceutical composition.
4. 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.
5. The method of claim 1 , 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.
6. The method of claim 1 , wherein the subject has: 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.
7. The method of claim 1 , wherein the statin therapy comprises administering to the subject a statin and optionally ezetimibe.
8. 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.
9. 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.
10. The method of claim 1 , wherein the pharmaceutical composition is formulated to delay onset of a first said cardiovascular event of said subject compared with control subjects, wherein each said control subject is on stable statin therapy, has a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL, and has established cardiovascular disease.
11. The method of claim 10 , wherein the medicament is formulated to delay onset of a second said cardiovascular event of said subject compared with control subjects.
12. The method of claim 10 , wherein the subject has diabetes mellitus and the control subjects each have diabetes mellitus.
13. The method of claim 10 , wherein the subject has metabolic syndrome and the control subjects each have metabolic syndrome.
14. The method of claim 1 , wherein the administration further reduces the risk of stroke and/or risk of myocardial infarction.
15. A method of reducing risk of a cardiovascular event in a subject on statin therapy with residual atherogenic dyslipidemia and clinically evident cardiovascular disease, the method comprising administering to the subject a pharmaceutical composition comprising about 4 g of eicosapentaenoic acid in triglyceride form per day for a period of at least about 2 years, wherein said administration reduces risk of cardiovascular death, need for coronary revascularization, risk of unstable angina, risk of stroke and/or risk of myocardial infarction.
16. The method of claim 15 , wherein the composition is administered to the subject in 1 to 4 dosage units per day.
17. The method of claim 15 , wherein the eicosapentaenoic acid in triglyceride form comprises at least about 96 wt. % of all omega-3 fatty acids in the pharmaceutical composition.
18. The method of claim 15 further comprising a step of measuring the subject's baseline lipid profile prior to administering the pharmaceutical composition to the subject.
19. The method of claim 15 , 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.
20. The method of claim 15 , wherein the subject has: 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.
21. The method of claim 15 , wherein the statin therapy comprises administering to the subject a statin and optionally ezetimibe.
22. The method of claim 15 , 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.
23. The method of claim 15 , wherein the subject is administered about 4 g of the pharmaceutical composition per day for at least about 3 years.
24. The method of claim 15 , wherein the pharmaceutical composition is formulated to delay onset of a first said cardiovascular event of said subject compared with control subjects, wherein each said control subject is on stable statin therapy, has a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL, and has established cardiovascular disease.
25. The method of claim 24 , wherein the first cardiovascular event of the subject is stroke and/or myocardial infarction.
26. The method of claim 24 , wherein the first cardiovascular event of the subject and the first cardiovascular event of the control subjects is stroke.
27. The method of claim 24 , wherein the first cardiovascular event of the subject and the first cardiovascular event of the control subjects is myocardial infarction.
28. The method of claim 24 , wherein the medicament is formulated to delay onset of a second said cardiovascular event of said subject compared with control subjects.
29. The method of claim 24 , wherein the subject has diabetes mellitus and the control subjects each have diabetes mellitus.
30. The method of claim 24 , wherein the subject has metabolic syndrome and the control subjects each have metabolic syndrome.