PHARMACEUTICAL COMPOSITIONS COMPRISING EPA AND A CARDIOVASCULAR AGENT AND METHODS OF USING THE SAME

1 . A composition comprising eicosapentaenoic acid and docosahexaenoic acid in free acid form, at least one surfactant and at least one cardiovascular agent.

2 . The composition of claim 1 further comprising at least one additional fatty acid selected from the group consisting of linolenic acid, arachidonic acid, alpha-linolenic acid, stearadonic acid, eicosatrienoic acid, docosapentaenoic acid, heneicosapentaenoate, gamma-linolenic acid, or ethyl esters or tryglycerides thereof.

3 . The composition of claim 1 further comprising oleic acid or a derivative thereof.

4 . The composition of claim 1 wherein the composition comprises at least 90% omega-3 fatty acids, by weight of total fatty acid present in the composition.

5 . The composition of claim 1 having a ratio of eicosapentaenoic acid to docosahexaenoic acid from about 2:1 to about 19:1, and wherein the eicosapentaenoic acid and docosahexaenoic acid combined comprise more than about 50% by weight of total fatty acid present in the composition.

6 . The composition of claim 1 wherein the at least one surfactant is selected from the group consisting of quaternary ammonium compounds, dioctyl sodium sulfosuccinate, polyoxyethylene alkylphenyl ethers, poloxamers, polyoxyethylene fatty acid glycerides and oils, polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan esters, propylene glycol fatty acid esters, sodium lauryl sulfate, glyceryl fatty acid esters, sorbitan esters, tyloxapol, and mixtures thereof.

7 . The composition of claim 1 wherein the at least one surfactant is selected from the group consisting of polysorbate 20, polysorbate 80, and mixtures thereof.

8 . The composition of claim 1 wherein the at least one surfactant is present in an amount of about 0.25% to about 15% by total weight of the composition.

9 . The composition of claim 1 wherein the at least one cardiovascular agent is an HMG-CoA reductase inhibitor.

10 . The composition of claim 9 wherein the HMG-CoA reductase inhibitor comprises lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, fluvastatin, atorvastatin, simvastatin, or combinations thereof.

11 . The composition of claim 9 wherein the HMG-CoA reductase inhibitor is present in an amount from about 1 mg to about 1000 mg.

12 . The composition of claim 1 further comprising at least one antioxidant.

13 . The composition of claim 12 wherein the at least one antioxidant is a tocopherol.

14 . The composition of claim 12 wherein the antioxidant is present in an amount from about 0.0001% to about 5% of the total weight of the composition.

15 . A method of treating a cardiovascular-related disease in a subject in thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising: eicosapentaenoic acid, docosahexaenoic acid, at least one surfactant; and at least one cardiovascular agent.

16 . The method of claim 15 wherein the cardiovascular-related disease is selected from the group consisting of any disease or disorder of the heart or blood vessels or any symptom thereof, including, for example, acute cardiac ischemic events, acute myocardial infarction, angina, angina pectoris, arrhythmia, atrial fibrulation, atherosclerosis, arterial fibrillation, cardiac insufficiency, cardiovascular disease, chronic heart failure, chronic stable angina, congestive heart failure, coronary artery disease, coronary heart disease, deep vein thrombosis, diabetes, diabetes mellitus, diabetic neuropathy, diastolic dysfunction in subjects with diabetes mellitus, edema, essential hypertension, eventual pulmonary embolism, fatty liver disease, heart disease, heart failure, homozygous familial hypercholesterolemia (HoFH), homozygous familial sitosterolemia, hypercholesterolemia, ischemic complications in unstable angina and myocardial infarction, low blood pressure, metabolic syndrome, moderate to mild heart failure, myocardial infarction, obesity management, paroxysmal atrial/arterial fibrillation/fibrulation/flutter, paroxysmal supraventricular tachycardias (PSVT), particularly severe or rapid onset edema, platelet aggregation, primary hypercholesterolemia, primary hyperlipidemia, pulmonary arterial hypertension, pulmonary hypertension, recurrent hemodynamically unstable ventricular tachycardia (VT), recurrent ventricular arrhythmias, recurrent ventricular fibrillation (VF), ruptured aneurysm, sitisterolemia, stroke, supraventricular tachycardia, symptomatic atrial fibrillation/flutter, tachycardia, type-II diabetes, vascular disease, venous thromboembolism, ventricular arrhythmias, and combinations thereof.

17 . The method of claim 17 wherein the cardiovascular-related disease is selected from the group consisting of hyperlipidemia, hypertension, mixed dyslipidemia, and combinations thereof.

18 . The method of claim 17 wherein the cardiovascular-related disease is hypertriglyceridemia.

19 . The method of claim 17 wherein the administering step reduces fasting triglycerides by at least 10% compared to baseline or a placebo arm.

20 . The method of claim 17 wherein the administering step reduces fasting triglycerides by at least 15% compared to baseline or a placebo arm.

21 . The method of claim 17 wherein the administering step reduces fasting triglycerides by at least 20% compared to baseline or a placebo arm.

22 . The method of claim 17 wherein the administering step reduces fasting triglycerides by at least 25% and LDL-C by at least 5% compared to baseline or a placebo arm.

23 . The method of claim 17 wherein the administering step reduces fasting apolipoprotein B compared to baseline or a placebo arm.

24 . The method of claim 17 wherein the administering step reduces fasting apolipoprotein B by at least 5% compared to baseline or a placebo arm.

25 . The method of claim 17 wherein the administering step reduces fasting VLDL-C compared to baseline or a placebo arm.

26 . The method of claim 17 wherein the administering step reduces fasting VLDL-C by at least 15% compared to baseline or a placebo arm.

27 . The method of claim 17 wherein the pharmaceutical composition is administered to the subject in 1 to about 10 dosage units per day.

28 . The method of claim 27 wherein the dosage units comprise capsules.

29 . The method of claim 17 wherein the pharmaceutical composition is administered to the subject in 1 to about 4 dosage units per day.

30 . The method of claim 31 wherein the dosage units comprise capsules.