Expert Opinion on Optimising Guideline-Directed Medical Therapy and Expanding the Role of Angiotensin Receptor-Neprilysin Inhibitors (ARNIs) for Heart Failure Management in India

Strong clinical evidence and clear guideline recommendations support the use of guideline-directed medical therapy (GDMT) - particularly angiotensin receptor-neprilysin inhibitors (ARNIs) - in heart failure (HF) management, yet real-world adoption in India remains limited. Indian registry data indicate that just one quarter of patients leave the hospital with complete GDMT, and less than 5% receive ARNIs, even though robust evidence strongly favors these drugs. Hypotension, renal dysfunction, delayed initiation, and limited familiarity are common barriers that often also hinder optimal use. Sacubitril/valsartan has demonstrated consistent benefits not only in HF with reduced ejection fraction (HFrEF) but also in selected patients with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), especially women and those with borderline left ventricular ejection fraction, as shown in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) and Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction (PARAGON-HF) trials and supported by Indian ARNI PRESERVED study. The Safety, Tolerability and Efficacy of Rapid Up‑Titration of Guideline‑Directed Medical Therapies in Acute Heart Failure (STRONG-HF) trial validated rapid up-titration strategies, demonstrating that early high-intensity GDMT implementation with structured follow-up significantly reduces 180-day mortality and readmissions. Clinical experts recommend early in-hospital initiation of all four pillars of GDMT with flexible, patient-specific sequencing. Approaches such as simultaneous low-dose initiation, careful titration, and close monitoring can help manage tolerability concerns and improve adherence to ARNI therapy. Bridging the gap between guidelines and practice will require systemic interventions, including physician training, patient-centered care models, and devising research strategies such as national HF registries to understand and tailor therapeutic approaches from an Indian perspective.