MXPA01008213A - Essential fatty acids in the prevention of cardiovascular events - Google Patents

Abstract

The invention concerns the use of essential fatty acids with a high content in eicosapentaenoic acid ethyl ester (EPA) or docosahexaenoic acid ethyl ester (DHA) or a high concentration mixture thereof in the preparation of a medicament useful for preventing mortality, in particular due to sudden death, in patients who have suffered from a myocardial infarction.

Description

ESSENTIAL FATTY ACIDS IN THE PREVENTION OF CARDIOVASCULAR EVENTS DESCRIPTION OF THE INVENTION This invention relates to the use of a pharmaceutical composition containing ethyl esters of essential fatty acids originating from fish oils, in particular as a mixture of high concentration of ethyl esters of (20: 5? 3) eicosapentaenoic acid (EPA) and (22: ß? 3) docosahexaenoic acid (DHA) in the prevention of cardiovascular events, specifically mortality in patients who have survived the acute myocardial infarction hospitalization phase (AMI) ). It is well known that certain essential fatty acids contained in fish oil have a therapeutic effect in the prevention and treatment of cardiovascular disorders, such as in the treatment of thrombosis, hypercholesterolemia, arteriosclerosis, cerebral infarction and hyperlipemia. U.S. Patent Nos. 5,502,077, US 5,656,667 and US 5,698,594 can be cited as examples. REF: 131868 From the previous prior art, it is known in particular the utility of the fatty acids belonging to the family? -3, more specifically (20: 5? 3) eicosapentaenoic acid (EPA) and (22: 6? 3) Docosahexaenoic acid (DHA) in the treatment of the disorders mentioned above. The EPA actually, being a precursor of PGI3 and TxA 3, exerts a platelet aggregation prevention and an antithrombotic effect that can be assigned to the inhibition of cyclooxygenase (similar to aspirin effect) and / or to competition with arachidonic acid by this enzyme, with consequent reduction in the synthesis of PGE2 and TxA2, which are well-known platelet aggregation agents. On the other hand, DHA is the most important component of brain lipids in man and also, being a structural component of cellular platelets, indirectly intervenes in the increase of platelet fluidity, thus playing an important role in the activity antithrombotic International patent application W089 / 11521, the description of which is incorporated for reference, describes in particular an industrial process for the extraction of mixtures with a high content of polyunsaturated acids, including EPA and DHA and their ethyl esters, of oils animals and / or vegetables. The mixtures of the fatty acids, especially EPA / DHA, obtained according to W089 / 11521, are reported as being particularly useful in the treatment of cardiovascular diseases. However, currently the treatments used in human therapy have been shown to be insufficient in the prevention of cardiovascular events, and more specifically in mortality, in particular due to sudden death, which occurs in patients who have had a heart attack. myocardium, due to recurrences after a first episode of acute myocardial infarction. Therefore, there is still a need for an effective drug, in particular for the prevention of these recurrences. The object of this invention, therefore, is the use of essential fatty acids with a high content of ethyl ester-EPA or ethyl ester-DHA or a mixture of high concentration thereof, in the preparation of a useful medicament for the prevention of mortality, due, for example, to cardiovascular events or sudden death, in patients who have suffered from a myocardial infarction. According to a preferred aspect, this invention therefore provides the use of essential fatty acids with a high content of ethyl ester-EPA or ethyl ester-DHA or a mixture of high concentration thereof, in the preparation of a useful drug for the prevention of sudden death in patients who have suffered from a myocardial infarction. For ease of description the "ethyl ester-EPA" and the "ethyl ester-EHA" will also be cited as "EPA" and "DHA". An essential fatty acid with a high content of ethyl ester-EPA or ethyl ester-DHA, in accordance with the present invention, preferably contains more than 25% by weight (b.w.), in particular from about 60 to about 100% of such ester. These compounds can be obtained by known methods. In an essential fatty acid with a high concentration mixture of ethyl ester-EPA and ethyl ester-DHA, preferably such mixture has an EPA + DHA content greater than 25% by weight, in particular from about 30 to about 100% by weight, preferably about 85% by weight. In the EPA / DHA mixture, EPA is preferably present in a percentage from about 40 to about 60% by weight and DHA, preferably in a percentage from about 25 to about 45-50%. In any case the preferred EPA / DHA ratio in such EPA / DHA mixture is about 0.9 / 1.5.

PHARMACOLOGY The effectiveness of the treatment, according to the invention, is, for example, proven by the fact that a highly significant and surprising reduction in post-infarction mortality was observed by such treatment in a clinical trial that lasted for 3.5 years. , with protocols substantially designated as follows: 1 a "control" group received standard therapy which is usually given to infarcted patients; 2 a "treatment" group, in addition to the therapy given to the "control" group, received 85% EPA + DHA (1 g daily); 3 a "treatment" group, in addition to the therapy given to the "control" group, received vitamin E; Y 4 A "treatment" group, in addition to the therapy given to the control group, received 85% vitamin E and EPA + DHA (1 g daily).

In fact, the patient group "treated" according to protocol 2 showed, compared to the "control" group 1, a decrease of approximately 20% in total mortality, with a decrease of approximately 40% in mortality due to sudden death and a marked reduction in mortality due to other cardiovascular events. Conversely, no significant results were achieved in group 3 compared with control group 1, since it was a total mortality reduction of approximately 19% in group 4 compared to the control group, with results that were similar to those obtained in the treated group 2. From the above clinical results, the person skilled in the art will appreciate that, the use of a pharmaceutical composition according to the present invention is certainly useful in human therapy in the prevention of mortality in patients who have suffered from a myocardial infarction. Accordingly, this invention provides a method for the prevention of mortality in a patient who has survived a myocardial infarction, comprising administering to such a patient a therapeutically effective amount of a medicament containing essential fatty acids with a high content. in ethyl ester-EPA or ethyl ester-DHA or a mixture of high concentration thereof. As it is known, sudden death is an important contributor to the proportion of mortality in patients with heart disease, counting over 450,000 deaths per year in the United States of America. Approximately 80% of patients, particularly those survivors of acute myocardial infarction with low ventricular ejection fractions, are at high risk of sudden death or reinfarction. The above clinical results show that the present invention provides a valuable and novel therapeutic tool for the prevention of sudden death in patients, in particular in those who survive acute myocardial infarction. Accordingly, as a preferred aspect, the present invention also provides a method for the prevention of sudden death in a patient, who is a survivor of myocardial infarction, comprising administering to such a patient a therapeutically effective amount of a medicament that it contains essential fatty acids with a high content of ethyl ester-EPA or ethyl ester-DHA or a mixture of high concentration thereof. The essential fatty acids, according to the invention, can either have a high content, for example more than 25% by weight in ethyl ester-EPA or ethyl ester-DHA or in a mixture thereof. However, the ethyl ester-EPA and the ethyl ester-DHA are preferably present as a mixture thereof with an EPA + DHA content greater than 25% by weight, in particular from about 30 to about 100% by weight, preferably about 85% by weight. Based on the clinical results obtained, according to a preferred aspect of the invention, the dosage of an essential fatty acid containing a mixture of EPA + DHA with a titre of 85% by weight for oral administration to a patient can vary from approximately 0.7 g approximately 1.5 g daily, preferably about 1 g daily. This amount of the product as a mixture of EPA + DHA (or amount of ethyl ester-EPA alone or ethyl ester-DHA alone) can be administered in several divided doses throughout the day or preferably in a single administration, to achieve the level desired blood Obviously it is at the doctor's discretion to adjust the amount of the product to be administered according to the age, weight and general conditions of the patient. The medicament, for example in the form of a pharmaceutical composition, according to this invention can be prepared according to methods known in the art. The preferred route of administration is oral, however, leaving alternative routes of administration, such as the parenteral route at the doctor's discretion. The following examples illustrate the preferred formulations for oral administration, but do not attempt to limit the invention in any way.

Gelatin capsules According to known pharmaceutical techniques, capsules having the subsequent composition and containing 1 g of the active ingredient (EPA + DHA, title 85%) per capsule are prepared.

Formulation 1 ethyl ester-EPA 525 mg / capsule; ethyl ester-DHA 315 mg / capsule; d-alpha tocopherol 4 IU / capsule; gelatin 246 mg / capsule; glycerol 118 mg / capsule; red iron oxide 2.27 mg / capsule; yellow iron oxide 1.27 mg / capsule; Formulation 2 Ethyl esters of polyunsaturated fatty acids 1000 mg containing ethyl esters of polyunsaturated esters? -3 (eicosapentaenoic EPA, docosahexaenoic acid (DHA) 850 mg tocopherol 0.3 mg gelatin succinate 233 mg glycerol 67 mg p Sodium oxybenzoate 1.09 mg propyl sodium p-oxobenzoate 0.54 mg It is noted that in relation to this date the best method known by the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (9)

CLAIMS Having described the invention as above, the contents of the following claims are claimed as property:

1. The use of essential fatty acids containing a mixture of ethyl ester of eicosapentaenoic acid

(EPA) and ethyl ester of docosahexaenoic acid (DHA) in the preparation of a medicament useful for the prevention of mortality in a patient who has suffered from a myocardial infarction where the content of EPA + DHA in such a mixture is greater than 25% by weight; and the medication is for oral administration. 2. The use according to claim 1, wherein the medicament is useful for the prevention of mortality due to sudden death in a patient who has suffered from a myocardial infarction.

3. The use according to claim 1 or 2, wherein the content of EPA + DHA in the mixture is from about 30 to about 100% by weight.

4. The use according to claim 1 or 2, wherein the content of EPA + DHA in the mixture is approximately 85% by weight.

5. The use according to claim 4, wherein the medicament is for oral administration, in a dose from about 0.7 g to about 1.5 g daily.

6. The use according to claim 5, wherein the EPA / DHA ratio in the EPA + DHA mixture is approximately 0.9 / 1.5.

7. The use of essential fatty acids containing ethyl ester of eicosapentaenoic acid (EPA) and ethyl ester of docosahexaenoic acid (DHA) in the preparation of a medicament useful for the prevention of mortality in a patient who has suffered from a myocardial infarction, where the content of EPA or DHA is greater than 25% by weight; and the medication is for oral administration.

8. The use according to claim 7, wherein the medicament is useful for the prevention of mortality due to sudden death in a patient who has suffered from a myocardial infarction. The use according to claim 7 or 8, wherein the content of EPA or DHA is from about 60 to about 100% by weight.