Real-World Evaluation of the Dosage Patterns and Safety of Angiotensin Receptor-Neprilysin Inhibitor Therapy in Indian Patients With Heart Failure With Reduced Ejection Fraction: The ADD-ARNI Study Protocol.

backgroundHeart failure is a burgeoning disease that imposes an enormous social and economic burden globally. It presents a significant public health challenge due to its high morbidity and mortality. In recent years, notable advancements have been made in the pharmacological treatment of heart failure with reduced ejection fraction (HFrEF), with guideline-directed medical therapy (GDMT) emerging as the cornerstone of HFrEF management. Although the angiotensin-receptor neprilysin inhibitor (ARNI), sacubitril/valsartan, is recognized as an integral component of HFrEF pharmacotherapy, variations in dose response have been observed in the Indian population. Furthermore, substantial differences exist in heart failure management practices across various types of hospitals in India. To address this paucity, the Assessing the Dosage Pattern and Demographic Characteristics in Heart Failure Reduced Ejection Fraction Patients Initiated with Angiotensin Receptor-Neprilysin Inhibitor in India (ADD-ARNI) study was designed to characterize contemporary HFrEF pharmacotherapy in India. This is a prospective, multicenter observational study to evaluate the dosage patterns, treatment adherence, and safety of ARNI therapy in HFrEF patients in India.

methodsThe ADD-ARNI study is a prospective, multicenter, observational study designed to enroll 3000 patients diagnosed with HFrEF. The study population will consist of symptomatic chronic HFrEF patients who are eligible for the initiation of sacubitril/valsartan (ARNI) as per the clinical judgement of the treating physician. The primary endpoint of the study is the dosage pattern of sacubitril/valsartan at the start as well as the end of the study. The secondary endpoints include the dosing pattern of other concomitant HFrEF medications at the start and end of the study, such as the doses of beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and diuretics, the implementation of GDMT at the end of the study, the assessment of the effectiveness of sacubitril/valsartan therapy based on changes in functional capacity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels from baseline to follow-up, and the incidence of adverse events, either spontaneously reported by the patients or noticed by the clinician during the study.

conclusionIn heart failure management, there is an unmet clinical need to gain insights about the real-world evidence of pharmacotherapy, adherence to current practice guidelines, and impact on clinical outcomes. Undertreatment with doses less than 50% of the guideline-recommended target doses is associated with poorer prognosis. The ADD-ARNI study will provide real-world evidence on dosage patterns, effectiveness, treatment persistence, safety, and implementation of GDMT among Indian HFrEF patients treated with sacubitril/valsartan therapy.