Addressing the gaps in heart failure management: Spotlight on the mineralocorticoid receptor antagonist utilization in India

INTRODUCTION Mineralocorticoid receptor antagonists (MRAs) are a cornerstone of evidence-based therapy for heart failure (HF), with trials showing major mortality and morbidity benefits.[1] However, a recent survey of 528 Indian physicians showed a wide gap between guideline recommendations and clinical practice.[2] While 88.6% of doctors acknowledge MRAs as beneficial, only about 37% use them as first-line HF therapy. This reluctance is striking given that MRAs are class-I guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) in international and Indian guidelines.[3,4] By contrast, 92% of physicians add MRAs to patients already on diuretics or other therapies, rather than initiating MRAs upfront. A cross-sectional study, “Current Practice and Perceptions on the Use of MRAs in the Management of HF: A Cross-sectional Study Among Indian Physicians,” published in this issue of the journal, offers invaluable insights into the real-world application of MRAs in HF management.[2] We examine the study’s findings within the broader context of global HF care disparities and propose actionable strategies to bridge the knowledge-to-practice gap in MRA utilization. CURRENT MINERALOCORTICOID RECEPTOR ANTAGONIST UTILISATION: INSIGHTS AND DISCREPANCIES The study by Garg et al. reveals several aspects of GDMT initiation and MRA utilization patterns among Indian physicians. A noteworthy finding was the approach to initiating GDMT: 60% of physicians preferred to start drugs in parallel, while 40% opted for sequential addition. This observation is particularly pertinent as recent guidelines for HF management strongly advocate for the parallel initiation of all four pillars of GDMT – Renin–angiotensin–aldosterone System inhibitors (RAASi), Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i), Beta-blockers, and MRAs.[5] The rationale behind parallel initiation is that the efficacy of one GDMT drug does not negatively impact the efficacy of another. Simultaneous introduction can reduce the risk of hospitalizations and all-cause mortality, ultimately improving patient survival. Sequential therapy, conversely, delays the full therapeutic effect, as the next drug can only be added after achieving the target dose of the previous one.[6] However, the guidelines also emphasize individualizing sequencing/titration according to blood pressure, renal function, potassium, and tolerability. The fact that 40% of physicians still prefer sequential therapy indicates a significant gap in the adoption of optimal, evidence-based practices in India. Regarding the specific role of MRAs as first-line therapy, only 37.1% of physicians preferred MRAs, placing them slightly ahead of beta-blockers (33.1%), but considerably more preferred to initiate ARNI (23.8%) or SGLT2i (6%) as first-line treatments. This distribution suggests that while MRAs are generally acknowledged, they are not consistently seen as the immediate first-line option by physicians, further reinforcing the notion that sequential, rather than parallel, initiation of GDMTs is prevalent. The study explicitly highlighted the need for increased awareness among physicians regarding the parallel use of all four GDMT drugs, including MRAs, as first-line therapy in HF. Despite the hesitation in using MRAs as first-line therapy, the overall preference for MRAs in HF management was high, with 88.7% of physicians indicating they preferred using them. This preference largely stemmed from the recognition of MRAs’ dual properties as both diuretics and disease-modifying agents, cited by 81.4% of physicians. Furthermore, 92% of physicians reported co-prescribing MRAs with loop diuretics. This widespread co-prescription underscores a practical understanding of their complementary roles in fluid management in HF. When it came to the choice between available MRAs, spironolactone was preferred by 54.7% of physicians, while 45.3% chose eplerenone. Real-world data from both India and Western countries have shown similar composite benefits in terms of reduction in cardiovascular mortality, hospitalization, left ventricular ejection fraction, and left ventricular diameter for both drugs. The choice of a particular MRA brand was primarily influenced by perceptions of quality (77.7% of physicians), followed by cost (58.5%), availability (48.1%), and, to a lesser extent, reminders from medical representatives (18.4%). The emphasis on cost and availability is particularly relevant in the Indian context, where a significant portion of patients lack insurance coverage and bear treatment expenses out-of-pocket, and vast economic, healthcare, and geographical disparities can affect drug accessibility.[7]Figure 1 lists the common barriers to MRA implementation in clinical practice.Figure 1: The common barriers to mineralocorticoid receptor antagonist utilization in the management of patients with heart failureDOSING, MONITORING, AND PERCEIVED BENEFITS The study provided important details on MRA dosing and monitoring practices. The initial spironolactone dose of 25 mg was preferred by 77.8% of physicians, which aligns with recommendations from experts in India and the RALES investigators, who found this dose effective and safe in combination with other HF medications.[8,9] However, 22.2% of physicians initiated MRAs at a higher dose of 50 mg. The standard recommended starting dose is 25 mg once daily, provided serum potassium is ≤5.0 mEq/L and eGFR is adequate (>50 mL/min/1.73 m²); if well tolerated, the dose may be increased to 50 mg once daily. Dose titration was predominantly guided by serum potassium levels, with 97.5% of physicians adapting the dose based on this parameter. In patients concurrently on beta-blockers, 67.6% of physicians preferred to titrate the MRA dose as tolerated by the patient. Physicians reported several significant clinical benefits associated with MRA therapy. The most frequently cited outcomes were an improvement in the New York Heart Association functional class (41.1% of physicians) and a reduction in hospitalization episodes (32.6% of physicians). Other reported benefits included positive cardiac remodeling and symptomatic relief. These perceived benefits are consistent with existing literature, including the Trivandrum HF Registry, which reported that discharge prescription of an MRA was associated with a 25% lower adjusted risk of 5-year mortality (HR 0.75, 95% confidence interval 0.64–0.88).[10] This observational finding is consistent with randomized evidence from RALES, in which spironolactone 25 mg daily reduced mortality and HF hospitalizations.[5] THE PERSISTENT CHALLENGE: UNDERDOSING AND UNDERUTILISATION Despite the recognized benefits and widespread preference for MRAs, the study revealed a significant gap in clinical practice: 84.5% of physicians agreed that patients receiving MRAs are underdosed, and 83.4% considered MRAs to be underutilized in the management of HF in India. These perceptions are not unique to India, as MRA underutilization has been reported across Asia, the USA, and Europe. For instance, data from the Swedish HF Registry indicated that MRAs were prescribed in only 40% of patients,[7] and the CHAMP-HF registry in the U.S. showed that two out of three eligible HF patients were not prescribed the therapy.[11] The primary barrier for not considering MRA as first-line HF treatment in India, as cited by 43.8% of physicians, was a lack of awareness. Other significant hindering factors included the perception of MRAs as merely a diuretic (28%), concerns about hyperkalemia (18%), and the perception of MRAs as a “specialty molecule” (10%). The fear of hyperkalemia as a side effect is a common reason for under-prescribing MRAs. However, this study offered a reassuring perspective: 80.9% of physicians reported that hyperkalemia (>5.0 mmol/L) occurred in