Use of a combination of levosimendan and an sglt-2 inhibitor to treat heart failure

A pharmaceutical composition comprising levosimendan, its metabolites OR-1896 or OR-1855, or a combination thereof, a SGLT-2 inhibitor, and a pharmaceutically acceptable carrier, preferably wherein the SGLT-2 inhibitor is empagliflozin;

• or
• a pharmaceutical composition comprising an amount of a SGLT-2 inhibitor and an amount of levosimendan, its metabolites OR-1896 or OR-1855, or a combination thereof, for use in treating a subject afflicted with heart failure, wherein the SGLT-2 inhibitor and the levosimendan, its metabolites OR-1896 or OR-1855, or a combination thereof, are administered simultaneously, contemporaneously or concomitantly;
• preferably wherein the heart failure is heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) or pulmonary hypertension with heart failure with reduced ejection fraction (PH-HFrEF);
• and/or
• preferably wherein the SGLT-2 inhibitor is selected from the group consisting of empagliflozin, canagliflozin, ertugliflozin, or dapagliflozin;
• or
• a pharmaceutical composition in unit dosage form, useful in treating a subject afflicted with heart failure, which comprises:
• e) an amount of levosimendan;
• and
• f) an amount of an SGLT-2 inhibitor,
• wherein the respective amounts of said levosimendan and said SGLT-2 inhibitor in said composition are effective, upon concomitant administration to said subject of one or more said unit dosage forms of said composition, to achieve a greater than additive therapeutic result in treating the subject;
• preferably wherein the SGLT-2 inhibitor is selected from the group consisting of empagliflozin, canagliflozin, ertugliflozin, or dapagliflozin, and the heart failure is heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) or pulmonary hypertension with heart failure with reduced ejection fraction (PH-HFrEF);
• or
• a package comprising:
• a) a first pharmaceutical composition comprising an amount of levosimendan and a pharmaceutically acceptable carrier;
• b) a second pharmaceutical composition comprising an amount of an SGLT-2 inhibitor and a pharmaceutically acceptable carrier;
• and
• c) instructions for use of the first and second pharmaceutical compositions together to treat a subject afflicted with heart failure;
• preferably wherein the SGLT-2 inhibitor is empagliflozin and the heart failure is heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) or pulmonary hypertension with heart failure with reduced ejection fraction (PH-HFrEF);
• or
• a therapeutic package for dispensing to, or for use in dispensing to, a subject afflicted with heart failure, which comprises:
• a) one or more unit doses, each such unit dose consisting essentially of:
• i) an amount of levosimendan;
• and
• ii) an amount of an SGLT-2 inhibitor,
• wherein the respective amounts of said levosimendan and said SGLT-2 inhibitor in said unit dose are effective, upon concomitant administration to said subject, to achieve a greater than additive therapeutic result in treating the subject, and
• b) a finished pharmaceutical container therefor, said container containing said unit dose or unit doses, said container further containing or comprising labeling directing the use of said package in the treatment of said subject;
• preferably wherein the SGLT-2 inhibitor is selected from the group consisting of empagliflozin, canagliflozin, ertugliflozin, or dapagliflozin, and the heart failure is heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) or pulmonary hypertension with heart failure with reduced ejection fraction (PH-HFrEF).

Use of a SGLT-2 inhibitor in combination or as an add-on with a therapy that includes levosimendan, its metabolites OR-1896 or OR-1855, or a combination thereof, to treat a subject afflicted with heart failure, wherein the SGLT-2 inhibitor and the levosimendan, its metabolites OR-1896 or OR-1855, or a combination thereof are administered simultaneously, contemporaneously or concomitantly;

• preferably wherein the SGLT-2 inhibitor is selected from the group consisting of empagliflozin, canagliflozin, ertugliflozin, or dapagliflozin;
• and/or
• preferably wherein the heart failure is heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) or pulmonary hypertension with heart failure with reduced ejection fraction (PH-HFrEF);
• or
• use of a SGLT-2 inhibitor in the manufacturing of a medicament for use in combination with or as an add-on to a therapy that includes levosimendan, its metabolites OR-1896 or OR-1855, or a combination thereof, to treat a subject afflicted with heart failure, wherein the SGLT-2 inhibitor and the levosimendan, its metabolites OR-1896 or OR-1855, or a combination thereof are administered simultaneously, contemporaneously or concomitantly;
• preferably wherein the heart failure is heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) or pulmonary hypertension with heart failure with reduced ejection fraction (PH-HFrEF);
• and/or
• preferably wherein the SGLT-2 inhibitor is selected from the group consisting of empagliflozin, canagliflozin, ertugliflozin, or dapagliflozin.