Combination therapy of angiotensin converting enzyme inhibitor and aldosterone antagonist for reducing morbidity and mortality from cardiovascular disease
AssigneeG.D. Searle & Co.
InventorsAlfonzo T. Perez, Debra J. Asner, Richard J. LaChapelle, John C. Alexander, Barbara Roniker
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Abstract
Combinations of an ACE inhibitor, an aldosterone antagonist, and a loop diuretic are described for use in treatment of circulatory disorders. Of particular interest are therapies using captopril, enalapril or lisinopril co-administered with spironolactone. This co-therapy would be particularly useful to reduce the death rate or the number of non-fatal hospitalizations or prevent the progression of congestive heart failure in patients with cardiovascular disease.
Claims64
A co-therapy for treating a cardiovascular disorder in a subject, wherein said co-therapy comprises administering a therapeutically-effective amount of an angiotensin converting enzyme inhibitor and administering an aldosterone antagonist in an amount therapeutically effective to antagonize aldosterone to reduce the death rate or the number of non-fatal hospitalizations as compared to monotherapy with an angiotensin converting enzyme inhibitor.
A combination therapy for treating a cardiovascular disorder in a subject, wherein said combination therapy comprises administering an angiotensin converting enzyme inhibitor, an aldosterone antagonist and a loop diuretic to the subject, and wherein the angiotensin converting enzyme inhibitor, the aldosterone antagonist and the loop diuretic are administered at doses that in combination result in a statistically significant reduction in the death rate or the number of non-fatal hospitalizations as compared to said combination therapy without the aldosterone antagonist, and wherein said loop diuretic has no substantial aldosterone antagonistic effect.
A combination therapy for treating a cardiovascular disorder in a subject, wherein said combination therapy comprises administering an angiotensin converting enzyme inhibitor, an aldosterone antagonist and a loop diuretic to the subject, and wherein the angiotensin converting enzyme inhibitor, the aldosterone antagonist and the loop diuretic are administered at doses that in combination result in a statistically significant reduction in the death rate as compared to said combination therapy without the aldosterone antagonist, and wherein said loop diuretic has no substantial aldosterone antagonistic effect.
A combination therapy for treating a cardiovascular disorder in a subject, wherein said combination therapy comprises administering an angiotensin converting enzyme inhibitor, an aldosterone antagonist and a loop diuretic to the subject, and wherein the angiotensin converting enzyme inhibitor, the aldosterone antagonist and the loop diuretic are administered at doses that in combination result in a statistically significant reduction in the number of non-fatal hospitalizations as compared to said combination therapy without the aldosterone antagonist, and wherein said loop diuretic has no substantial aldosterone antagonistic effect.
A combination therapy for treating a cardiovascular disorder in a subject, wherein said combination therapy comprises administering an angiotensin converting enzyme inhibitor, an aldosterone antagonist and a loop diuretic to the subject, and wherein the angiotensin converting enzyme inhibitor, the aldosterone antagonist and the loop diuretic are administered at doses that in combination result in a statistically significant reduction in the rate of deaths resulting from sudden death in subjects afflicted with or susceptible to elevated heart rate variability as compared to said combination therapy without the aldosterone antagonist, and wherein said loop diuretic has no substantial aldosterone antagonistic effect.
A combination therapy for treating a cardiovascular disorder in a subject, wherein said combination therapy comprises administering an angiotensin converting enzyme inhibitor, an aldosterone antagonist and a loop diuretic to the subject, and wherein the angiotensin converting enzyme inhibitor, the aldosterone antagonist and the loop diuretic are administered at doses that in combination result in a statistically significant reduction in the death rate for deaths resulting from progression of heart failure as compared to said combination therapy without the aldosterone antagonist, and wherein said loop diuretic has no substantial aldosterone antagonistic effect.
A combination therapy for treating a cardiovascular disorder in a subject, wherein said combination therapy comprises administering an angiotensin converting enzyme inhibitor, an aldosterone antagonist and a loop diuretic to the subject, and wherein the angiotensin converting enzyme inhibitor, the aldosterone antagonist and the loop diuretic are administered at doses that in combination result in a statistically significant reduction in the death rate or the number of non-fatal hospitalizations in subjects having a left ventricular ejection fraction greater than about 26% as compared to said combination therapy without the aldosterone antagonist, and wherein said loop diuretic has no substantial aldosterone antagonistic effect.
A combination therapy for treating a cardiovascular disorder in a subject, wherein said combination therapy comprises administering an angiotensin converting enzyme inhibitor, an aldosterone antagonist and a loop diuretic to the subject, and wherein the angiotensin converting enzyme inhibitor, the aldosterone antagonist and the loop diuretic are administered at doses that in combination result in a statistically significant reduction in the death rate or the number of non-fatal hospitalizations in subjects having a left ventricular ejection fraction less than about 26% as compared to said combination therapy without the aldosterone antagonist, and wherein said loop diuretic has no substantial aldosterone antagonistic effect.
A combination therapy for treating a cardiovascular disorder in a subject, wherein said combination therapy comprises administering an angiotensin converting enzyme inhibitor, an aldosterone antagonist and a loop diuretic to the subject, and wherein the angiotensin converting enzyme inhibitor, the aldosterone antagonist and the loop diuretic are administered at doses that in combination suppress clinically significant cough due to elevated pulmonary arterial fibrosis or low levels of pulmonary blood pressure in the subject as compared to said combination therapy without the aldosterone antagonist, and wherein said loop diuretic has no substantial aldosterone antagonistic effect.
A combination therapy for treating a cardiovascular disorder in a subject, wherein said combination therapy comprises administering a therapeutically-effective amount of an angiotensin converting enzyme inhibitor, a therapeutically-effective amount of an aldosterone antagonist, a therapeutically-effective amount of a loop diuretic and a therapeutically-effective amount of digoxin to the subject.
A composition comprising an angiotensin converting enzyme inhibitor, an aldosterone antagonist, a loop diuretic and digoxin, and the pharmaceutically acceptable salts, esters and prodrugs thereof.
A composition of claim 63 comprising:
- a first amount of an angiotensin converting enzyme inhibitor, or a pharmaceutically acceptable salt, ester or prodrug thereof;
- a second amount of an aldosterone antagonist, or a pharmaceutically acceptable salt, ester or prodrug thereof;
- a third amount of a loop diuretic, or a pharmaceutically acceptable salt, ester or prodrug thereof;
- a fourth amount of digoxin, or a pharmaceutically acceptable salt, ester or prodrug thereof;
- and
- a pharmaceutically acceptable carrier;
- wherein the first, second, third and fourth amounts in combination comprise a therapeutically effective amount of said inhibitor, antagonist, loop diuretic and digoxin.
A composition of claim 64 wherein the aldosterone antagonist is spironolactone.
A composition of claim 64 wherein the aldosterone antagonist is eplerenone.
Dependencies are inferred from the claim text.