Dapagliflozin effects on hospitalization for heart failure reduction, and major adverse cardiovascular events

Abstract

Background Until recently, there are no available preventive measures for macrovascular complications of diabetes mellitus (DM). Sodium-glucose co-transporter inhibitors (SGLT-2i) are a relatively new class of medications with cardio-renal protection. However, it is unknown, whether this is a class effect. Also, the exact mechanisms of action are not fully understood. Aims The current review aimed to assess dapagliflozin effects on the major cardiovascular adverse events (MACE) and heart failure hospitalization rate (HHF) and its mechanisms of action. Methods The Pub Med, MEDLINE, and Google Scholar databases were systematically searched for relevant articles. Articles published in the English language from the first available article up to November 2019 were approached. The terms dapagliflozin, SGLT-2i, MACE, HHF, and mechanisms of action were used with proteans AND or OR. Out of two hundred-ten articles retrieved, only twenty-nine fulfilled the inclusion and exclusion criteria. Results Dapagliflozin reduced HHF, all-cause mortality, bumetanide induced hyperuricemia, and interstitial fluid volume with a lower rate of diuretic use. Possible mechanisms of action were: a reduction of oxidative stress, lowering of cardiac hexosamine biosynthetic pathway activation, reduced cytosolic sodium and calcium, and increased serum magnesium. Dapagliflozin effects on MACE are mixed. The above effects seem to be a class character across various population including normal people without diabetes with no differences across gender. Conclusion Dapagliflozin reduced HHF (superior to empagliflozin) and all-cause mortality. The drug acts at cellular levels and not simple diuresis and haemoconcentration.