Heart failure

SWAMY VIVEKANANDHA COLLEGE OF PHARMACY ELAYAMPALYAM, TIRUCHENGODE- 637205 STUDY PROTOCOL STUDY TITLE A CLINICAL EXPERIENCE ON DAPAGLIFLOZIN IN DIABETES MELLITUS PATIENTS WITH HFrEF - A PROSPECTIVE OBSERVATIONAL STUDY CLINICAL GUIDE Dr. S.P. Santhosh Kumar, MD, DNB (Cardio), Vivekanandha Medical Care Hospital, Elayampalayam INSTITUTIONAL GUIDE Dr. V. Shangavi, Pharm.D, Assistant Professor, Department of Pharmacy Practice. SUBMITTED BY: Manisha.B V- Pharm.D Narmadha.U V-Pharm.D Neesha Solanky.K V-Pharm.D Ramya.A V-Pharm.D Redlin Jani.R.R V-Pharm.D

A CLINICAL EXPERIENCE ON DAPAGLIFLOZIN IN DIABETES MELLITUS PATIENTS WITH HFrEF - A PROSPECTIVE OBSERVATIONAL STUDY INTRODUCTION: Heart failure (HF) can result from any structural or functional cardiac disorder that impairs ability of ventricle to fill with or eject blood characterized by dyspnoea, fatigue, exercise intolerance, and fluid retention, is associated with significant morbidity and mortality. HF can be broadly classified according to left ventricular (LV) ejection fraction (EF), and is therefore commonly referred to as HF with reduced EF (HFrEF; LVEF ≤ 40%), HF with mid-range or mildly reduced EF (LVEF 41–49%), or HF with preserved EF (LVEF ≥ 50%) Dapagliflozin a Sodium–Glucose co-transporter 2 (SGLT2) inhibitor, was recently approved in the USA and the EU for the treatment of adults with symptomatic heart failure with reduced ejection fraction (HFrEF). The cardiovascular (CV) benefits of dapagliflozin were first observed in the DECLARE-TIMI 58 trial, in which dapagliflozin 10 mg/day significantly reduced the risk of CV death or hospitalization for HF in patients with type 2 diabetes mellitus (T2DM) who had or were at risk for atherosclerotic CV disease. In the subsequent DAPA-HF trial, dapagliflozin 10 mg/day in addition to standard of care was associated with a significantly lower risk of worsening HF or CV death than placebo in patients with HFrEF, regardless of the presence or absence of T2DM. In renal Dapagliflozin is responsible for reabsorption of approximately 90% of the urinary glucose in the proximal tubule of the nephron. Inhibition of SGLT2 induces glycosuria, which is pronounced in hyperglycaemic individuals owing to the higher amounts of glucose filtered into the urine. The effect of glycosuria

diminishes with normalizing of blood glucose levels. In case with heart failure benefit, specific mechanisms have not been fully elucidated, but several putative mechanisms have been proposed. Among these are reduction in preload and afterload which improve the ventricular loading, improvement in myocardial metabolism and alterations of cardiac fibrosis. SGLT2 inhibitors also inhibit the sodium proton channel 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 remodelling. The benefits of dapagliflozin also remained consistent regardless of background HF therapies. Dapagliflozin was generally well tolerated, with an overall safety profile consistent with its known safety profile in other indications. AIM: To evaluate the clinical experience of Dapagliflozin in Diabetes Mellitus with Heart Failure reduced ejection fraction (HFrEF) patients in a tertiary care hospital. OBJECTIVE:  To evaluate the clinical improvement after the administration of Dapagliflozin in DM patients with HFrEF.  To assess the NT-pro BNP, Ejection fraction, HbA1c and Blood glucose levels.  To assess the Quality of Life using KCCQ (Kansas City Cardiomyopathy Questionnaire) scale.

METHODOLOGY: STUDY DESIGN – Prospective observational study STUDY SITE – Vivekanandha Medical Care Hospital STUDY PERIOD – 3-4 months STUDY POPULATION – 25-50 patients STUDY DEPARTMENT – Cardiology INCLUSION CRITERIA:  Patients with 35-70 years of age.  Both male and female patients will be included.  Patients with reduced Ejection fraction less than 40% in ECHO.  Patients with NT-pro BNP greater than 600 pg/ml.  Patients included in NYHA (class II – IV). EXCLUSION CRITERIA:  Patients with allergy or intolerance to any of the drug/study drug.  Patients above the age of 70 are excluded.  Patients belonging in NYHA class I are excluded.  Pregnant and lactating women are excluded.  Liver and renal failure patients are excluded.  Type I diabetic patients will be excluded.

STATISTICAL ANALYSIS: All data will be analyzed using Graph pad and Microsoft Excel. SOURCE OF DATA:  Patients data entry form  Designed data collection form  Medication chart  Lab investigations reports  Patient and patients caretaker interview METHOD OF STUDY: PHASE 1 – Data entry form was designed and all the relevant details of the patient will be included. PHASE 2 – NT-pro BNP, HbA1c, Ejection fraction and Blood glucose levels of each patients were noted. PHASE 3 – Patient interview and patient’s caretaker’s interview. PHASE 4 – All the data will be analyzed using Graph pad and Microsoft Excel. END POINTS PRIMARY ENDPOINT: NT-pro BNP, Echo, HbA1C, Blood Glucose. SECONDARY ENDPOINT: Body Weight, Blood Pressure, Heart Rate, Pulse Rate.

PLAN OF STUDY: Literature Review ↓ Designed protocol ↓ IEC approval ↓ Inclusion and Exclusion criteria ↓ Study population based on inclusion and exclusion criteria ↓ Data collection from patient’s ↓ Obtaining informed consent form ↓ Obtaining lab investigation -NT-pro BNP, Ejection fraction, HbA1c, Blood Glucose levels ↓ Analysis of the collected data ↓ Interpretation of the data ↓ Study outcome

STUDY OUTCOME:  The efficacy of dapagliflozin in heart failure will be analyzed.  Polypharmacy in diabetic patients with heart failure will be reduced.  Hospitalization of heart failure will be reduced.