The present application relates to compositions, kits, uses, systems and methods of using
naltrexone and
bupropion, or pharmaceutically acceptable salts thereof, for reducing the risk of adverse cardiovascular outcomes or events, including Major Adverse Cardiovascular Events (MACE) in subjects, preferably those at
increased risk of adverse cardiovascular outcomes of MACE, that may be
overweight or obese. The present application also relates to compositions, kits, uses, systems and methods of using
naltrexone and
bupropion or pharmaceutically acceptable salts thereof for treatment of
overweight of
obesity in subjects, preferably at
increased risk of adverse cardiovascular outcomes or MACE, wherein the treatment reduces the risk of MACE.