https://meditropics.com/dapaglifozin-in-hfref/

DYNAMIC DRUGS

Kiran*

Postgraduate Resident, Department of Medicine, LHMC, New Delhi

 

The Incidence of HF in India varies widely from 8 to 10 million with HFrEF being predominantly observed in 53% of population. Indian patients present with HF at a younger age. Prevalence of hypertension and diabetes as comorbidities are very high. Hospital-stay in Indian HF patients is higher due to higher prevalence of comorbidities. Prognosis of HF in Indian patients appears to be worse with In-hospital mortality of 9.7%. DAPA-HF trial is designed to prospectively evaluate the efficacy and safety of the SGLT2 inhibitor dapagliflozin in patients with heart failure and a reduced ejection fraction, regardless of the presence or absence of diabetes.

Dapagliflozin is a sodium-glucose co-transporter-2 (SGLT-2) inhibitor that reduces blood glucose in patients with type 2 diabetes mellitus (T2DM) by promoting glycosuria via inhibiting urinary glucose reabsorption and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion. In addition, it also enhances natriuresis, change tissue sodium handling, lower systolic blood pressure and reduce body mass. Early decreases in systolic blood pressure, weight and estimated glomerular filtration rate (eGFR), as well as increase in hematocrit are consistent with a diuretic action.

Specific mechanisms have not been known but putative mechanisms are reduction in preload and afterload (resulting in improvement in ventricular loading), improvement in myocardial metabolism and alterations of cardiac fibrosis. SGLT2 inhibitors have been shown to inhibit the sodium proton channel (NHE) in the cardiac myocytes that eventually leads to the reduction in intracellular calcium and mitochondria-induced cellular damage that lies at the heart of myocardial remodeling.

Indications for use of dapagliflozin in heart failure: – (prior to initiation BP, electrolytes, renal function and liver function should be monitored.)

Adults >18 years with: -Heart failure with a reduced left ventricular ejection fraction of 40% or less, Persistent symptoms despite optimized medications like ACE inhibitors, ARBs, beta blocker etc. (New York Heart Association (NYHA) class II to IV symptoms), With or without type 2 diabetes. It should be started at 10 mg once daily with no dose titration.

Contraindications: – Type 1 diabetes, Recurrent or particularly problematic hypoglycemia, Pregnancy or breast feeding, Hypersensitivity to dapagliflozin or lactose intolerant (excipient), Previous history of diabetic ketoacidosis (not seen in patients without diabetes).

Guidelines recommends at least 6 monthly reviews of patients with heart failure which should include monitoring BP and renal function.

This therapy is boon for HFrEF patients in India where considerable efforts are required to address significant unmet needs of frequent hospitalization, urgent visits to hospital emergency room and cardiovascular death in HF patients despite available therapies.