Methods for treatment of atherosclerosis
Disclosed herein are methods and compositions for preventing or treating atherosclerosis in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide and in some applications, a second active agent chemically linked to the peptide, to subjects in need thereof.
1. A method for delaying onset, ameliorating or eliminating statin side effects in a subject in need thereof, the method comprising administering an effective amount of a peptide D-Arg-2′6′-Dmt-Lys-Phe-NH 2 or a pharmaceutically acceptable salt thereof, wherein the peptide is chemically linked to the statin, wherein the statin side effect comprises one or more of rhabdomyolysis, kidney failure, diabetes, memory loss, and decreased coenzyme Q10 levels.
2. The method of claim 1 , wherein the statin is selected from the group consisting of: atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, niacin extended-release/lovastatin, lovastatin extended-release, amlodipine, atorvastatin, rosuvastatin, sitagliptin/simvastatin, fluvastatin, fluvastatin extended-release, atorvastatin, pitavastatin, lovastatin, pravastatin, niacin extended-release/simvastatin, ezetimibe/simvastatin, and simvastatin.
3. The method of claim 1 , wherein the pharmaceutically acceptable salt comprises acetate salt or trifluoroacetate salt.
4. The method of claim 1 , wherein the peptide and the statin are linked using a labile linkage that is hydrolyzed in vivo to release the peptide and the statin.
5. The method of claim 1 , wherein the statin comprises atorvastatin or rosuvastatin.
6. The method of claim 4 , wherein the labile linkage comprises an ester linkage, a carbonate linkage, or a carbamate linkage.