Inerția terapeutică în managementul insuficienței cardiace: dovezi din registrele indiene și strategii de eliminare a decalajului în prescrierea terapiei medicale ghidate de recomandări

1. Heart failure clinical burden and outcome in India

1.1. Epidemiology and clinical profile

Heart failure (HF) is a major cardiovascular health issue, with substantial mortality, hospitalization, impaired quality of life and healthcare utilization, with a particularly important consequences in low- and middle-income countries, where access to specialist cardiovascular care and evidence-based therapies may be limited⁽¹⁾.

The 2025 ICMR-NCDIR heart failure registry demonstrated that Indian HF patients are often younger than those described in many Western cohorts, with more than 60% of participants residing in rural areas⁽²⁾. Among 6018 hospitalized patients, 10.2% were aged 16-40 years old, 53.3% were aged 41-64 years old, and 36.5% were aged ≥65 years old. Ischemic heart disease was the predominant etiology across age groups, while the 90-day mortality remained clinically important even among younger patients⁽²⁾.

The same registry demonstrated clinically important mortality even among relatively young patients, with 90-day mortality of 12.6%, 13.4% and 19% among young, middle aged and elderly patients, respectively⁽²⁾. These findings are clinically important, because heart failure in India cannot be regarded solely as a disease of advanced age, and delayed recognition and treatment may affect individuals during economically productive years⁽²⁾.

The National Heart Failure Registry (NHFR), including 10,851 consecutive patients from 53 tertiary hospitals across 21 Indian states, provided extensive contemporary data on acute decompensated heart failure in India⁽³⁾. The mean age was 59.9 years old; 31% of patients were women, ischemic heart disease accounted for 72% of heart failure etiology, while dilated cardiomyopathy accounted for 18%⁽³⁾.

The relatively young age of Indian HF population has also been demonstrated in regional registries, supporting the need for earlier identification of high-risk patients and timely implementation of disease-modifying therapy⁽⁴⁾. Regional registries, including the Himachal Pradesh Heart Failure Registry, further demonstrate heterogeneity in the clinical and etiological profile of Indian HF populations, including an important contribution from non-ischemic etiologies⁽⁴⁾.

1.2. Major Indian HF registries and treatment patterns

The National Heart Failure Registry was established to provide nationally representative information regarding heart failure etiology, treatment practices and clinical outcomes, because previously available Indian data were predominantly derived from individual centers or geographically restricted cohorts⁽⁵⁾.

The Indian College of Cardiology National Heart Failure Registry (ICCNHFR) provides complementary information on acute decompensated heart failure across multiple Indian hospitals, including treatment patterns, short-term mortality and rehospitalization⁽⁶⁾. The Cardiology Society of India Kerala Acute Heart Failure Registry (CSI-KHFR) represents another large Indian registry and provides important evidence regarding guideline-directed medical therapy (GDMT) prescription and outcomes in acute heart failure⁽⁷⁾. The Trivandrum Heart Failure provides longitudinal information on mortality and readmission and has demonstrated persistent gaps in disease-modifying therapy among patients with heart failure with reduced ejection fraction (HFrEF)⁽⁸⁾.

NHFR demonstrated that only 47.5% of eligible patients with HFrEF received GDMT, while angiotensin receptor-neprilysin inhibitor (ARNI) use remained particularly low, at 4.8%⁽³⁾. NHFR therefore demonstrated that, even in tertiary hospitals, approximately one-half of eligible patients did not receive the available disease modifying treatment combination considered appropriate for HFrEF⁽³⁾.

CSI-KHFR reported that only approximately 28% of patients with HFrEF received guideline-directed medical therapy, despite the established association between GDMT use and improved outcomes⁽⁷⁾. In CSI-KHFR, β-blockers and mineralocorticoid receptor antagonists were prescribed more frequently than angiotensin receptor/neprilysin inhibitor, while ARNI use remained particularly limited⁽⁷⁾.

ICCNHFR similarly demonstrated substantial treatment underuse with all guideline-based medical therapies prescribed to only 24.99% of patients at discharge⁽⁶⁾. Only 23.72% of patients in ICCNHFR continued the prescribed GDMT combination during the first 30 days after discharge, demonstrating that the prescribing gap may be accompanied by an early post-discharge adherence gap⁽⁶⁾.

ICMR-NCDIR registry also showed that β-blockers, ACEI/ARB, MRA and ARNI were prescribed at different frequencies across age groups, with ARNI prescribed in only 5.9-7.5% of patients during hospitalization⁽²⁾. More recent Indian evidence suggests that GDMT adoption may be improved in specialist centers, but substantial residual gaps remain in achieving comprehensive four-pillar therapy and target doses⁽⁹⁾. A 2026 tertiary center registry from eastern India reported that four pillar GDMT adoption increased from 48.6% in the first half of 2022 to 76.3% in the second half of 2024⁽⁹⁾. Despite this improvement, sacubitril/valsartan target dose attainment in the same registry was only 20%, demonstrating that the prescription of drug does not necessarily represent adequate optimization⁽⁹⁾.

This distinction is central to understanding the Indian GDMT gap, because treatment may fail at several sequential stages, including failure to prescribe, failure to initiate, failure to titrate and failure to maintain therapy⁽¹⁰⁾.

1.3. Mortality, hospitalization and readmission outcomes

NHFR reported a 90-day all-cause mortality of 14.2% and a 90-day readmission rate of 8.4% among 10,851 patients with acute decompensated heart failure⁽³⁾. Patients with HFrEF or heart failure with mildly reduced ejection fraction (HFmrEF) who did not receive GDMT had significantly poorer survival than those receiving GDMT, supporting the clinical importance of the prescribing gap⁽³⁾. The NHFR subsequently reported a cumulative one-year mortality of 22.1% among 10,850 patients, with a one-year readmission rate of 17.2%⁽³⁾.

Mortality varied substantially according to heart failure etiology, ranging from 13.8 deaths per 100 person year in peripartum cardiomyopathy to 92.9 deaths per 100 person year in infective endocarditis⁽¹¹⁾.

In Trivandrum Heart Failure Registry, one-year all-cause mortality was 30.8%, with the highest mortality risk occurring during the first three months after hospitalization⁽¹²⁾. Approximately 30.2% of patients in the Trivandrum registry experienced at least one readmission within one year, demonstrating the considerable post-discharge burden of heart failure in India⁽¹²⁾. Long-term data from the same registry demonstrated a five-year mortality of 59% and a median survival of approximately 3.1 years⁽¹²⁾. In that cohort, discharge prescription of β-blockers, renin-angiotensin system blockers and MRA was associated with a lower long-term mortality risk, strengthening the argument that improving GDMT implementation is clinically meaningful rather than merely a process-of-care objective⁽¹²⁾.

CSI-KHFR reported in-hospital mortality of 7% and a 90-day mortality of 11.6%, with the GDMT component independently associated with the 90-day mortality⁽⁷⁾. Collectively, Indian registry data therefore demonstrate a consistent pattern of high mortality and rehospitalization occurring alongside incomplete implementation of evidence-based pharmacotherapy^(3,8).

2. Contemporary evidence and implementation of GDMT in HFrEF

2.1. Four pillars of GDMT

The contemporary management of heart failure with reduced ejection fraction is based on four foundational pharmacological classes consisting of an angiotensin receptor-neprilysin inhibitor or ACE inhibitor/ARB and evidence-based β-blockers, an MRA and an SGLT2 inhibitor^(13,14). The addition of SGLT2 inhibitor to the established neurohormonal treatment framework transformed the conventional three-drug model into a four-pillar strategy⁽¹³⁾. The 2022 AHA/ACC/HFSA guideline formally incorporated SGLT2 inhibitors as one of the four major pharmacological classes for HFrEF⁽¹³⁾. The 2023 ESC focused update further strengthened the role of SGLT2 inhibition across the HF spectrum based on subsequent randomized evidence⁽¹⁵⁾.

2.1.1. ARNI/ACEI/ARB

Renin-angiotensin system inhibition remains a fundamental component of HFrEF therapy, because neurohormonal activation contributes directly to ventricular remodeling and disease progression⁽¹⁶⁾. Sacubitril/valsartan has become the preferred renin-angiotensin system strategy for many eligible patients because of evidence demonstrating superior clinical outcomes compared with ACE inhibition in HFrEF⁽¹⁶⁾. Indian consensus literature has emphasized that ARNI remains under-prescribed in India, despite its established clinical benefits⁽¹⁶⁾. Indian experts have also highlighted the importance of early ARNI initiation and appropriate dose escalation rather than prolonged exposure to low doses without an active optimization plan⁽¹⁶⁾.

2.1.2. Evidence-based β‑blockers

Evidence-based β‑blockers remain one of the foundational therapies for HFrEF, because they counter chronic sympathetic activation and reduce adverse ventricular remodeling⁽¹⁷⁾. Indian consensus recommendations emphasize the role of selective β1‑blockade, including bisoprolol, particularly in patients with heart failure and common comorbidities⁽¹⁷⁾. The continued underuse or under-titration of β‑blockers therefore represents a potentially modifiable component of therapeutic inertia⁽¹⁷⁾.

2.1.3. Mineralocorticoid receptor antagonists

MRA therapy forms the third foundational component of HFrEF treatment, providing mortality and hospitalization benefits when used in appropriate patients⁽¹³⁾. Fear of hyperkalemia and renal deterioration can lead to inappropriate retain or discontinuation of MRA therapy, making renal and electrolyte monitoring an important component of safe implementation⁽¹⁰⁾.

2.1.4. SGLT2 inhibitors

Dapagliflozin and empagliflozin have demonstrated benefits in HFrEF irrespective of diabetes status and, therefore, should not be considered merely glucose-lowering therapies^(18,19). In DAPA-HF, dapagliflozin reduced the risk of worsening heart failure or cardiovascular death and retained benefit in patients receiving background sacubitril/valsartan⁽²⁰⁾. In EMPEROR-Reduced, empagliflozin reduced the combined risk of cardiovascular death or heart failure hospitalization compared with placebo in patients with HFrEF⁽¹⁸⁾. The benefit of empagliflozin was observed across different background treatment combinations, supporting its use as an additive foundational therapy rather than requiring complete optimization of other drug classes beforehand⁽²¹⁾.

2.2. Clinical evidence and guideline recommendations

Contemporary treatment philosophy has shifted from sequential optimization of drug class at a time toward rapid establishment of all four foundational therapies at tolerable doses^(10,22). The rationale for rapid implementation is that each class provides partially independent biological and clinical benefit, while delaying initiation exposes patients to preventable residual risk⁽²²⁾. The STRONG-HF trial directly addressed the pace of GDMT optimization and demonstrated that an intensive strategy of early follow-up and rapid up-titration was feasible after acute heart failure hospitalization⁽²³⁾. The trial supports structured early post-discharge monitoring rather than waiting for routine follow-up intervals before increasing evidence-based therapies⁽²³⁾.

The EMPULSE trial further demonstrated that empagliflozin could be initiated during hospitalization for acute heart failure after clinical stabilization, supporting earlier treatment initiation⁽²⁴⁾. The TRANSITION study demonstrated that sacubitril/valsartan initiation before discharge or shortly after discharge was feasible in stabilized patients with HFrEF⁽²⁵⁾. Approximately half of the patients in TRANSITION achieved the target sacubitril/valsartan dose within 10 weeks, illustrating that dose optimization requires an active titration pathway rather than prescription alone⁽²⁵⁾. These findings collectively support a treatment model in which initiation and optimization are considered continuous processes beginning during hospitalization or at the first eligible outpatient encounter^(23,25).

2.3. Initiation, sequencing and dose optimization

Traditional sequencing frequently involved starting an ACEI/ARB, followed by a β-blocker and MRA, with the subsequent introduction of newer therapies, potentially delaying complete disease-modifying treatment for several months⁽²²⁾. Instead, contemporary implementation strategies emphasize achieving all four foundational classes early, even when individual agents initially remain at low doses⁽²²⁾. A rapid-sequencing strategy can therefore prioritize breadth of therapy before maximal dose escalation, provided the patient is clinically stable and the contraindications are assessed⁽²²⁾.

The precise sequence should be individualized according to blood pressure, heart rate, renal function, serum potassium, congestion and other clinical characteristics⁽¹⁰⁾. Hypotension, hyperkalemia and renal dysfunction are among the most frequently cited clinical barriers to GDMT implementation and should be managed rather than automatically interpreted as reasons for permanent treatment avoidance⁽²²⁾. Indian expert consensus similarly recommends patient profile-based implementation, because a uniform titration sequence may not be appropriate for patients with different blood pressure, renal and comorbidity profiles⁽²⁶⁾.

However, rapid optimization should not be interpreted as indiscriminate titration; patient selection, tolerability and appropriate monitoring remain essential, particularly in resource-constrained settings.

3. The GDMT implementation gap in Indian heart failure

3.1. Real-world utilization of GDMT

The Indian registry literature consistently demonstrates that evidence-based pharmacological therapy remains incompletely implemented, despite the availability of effective treatment^(3,7). The severity of the gap differs according to registry, patient population, HF phenotype and healthcare setting, but the direction of the evidence is consistent^(3,6). NHFR reported GDMT use in 47.5% of eligible HFrEF patients, whereas ICCNHFR reported complete GDMT prescription is only 24.99% of patients at discharge^(3,6). CSI-KHFR reported that only 28% of patients with HFrEF received GDMT, further demonstrating substantial under-treatment in routine Indian practice⁽⁷⁾. The Trivandrum registry reported that only 25% of patients with HFrEF were discharged on GDMT, despite the long-term survival implications of disease-modifying treatment⁽⁸⁾. The persistence of these gaps across geographically distinct Indian registries suggests that therapeutic inertia is unlikely to be explained by a single institutional prescribing practice^(3,8). The more recent eastern Indian registry provides evidence that systematic specialist care can substantially improve four-pillar adoption, but even optimized tertiary care did not achieve universal treatment⁽⁹⁾. This finding suggests that improvements in clinician awareness and specialist access can reduce the gap, but may not completely eliminate the structural, financial and clinical barriers that influence GDMT use^(9,27).

3.2. Four-pillar therapy and target-dose gap

A major limitation of evaluating GDMT only as a binary prescribing variable is that prescription does not establish whether the patient received an evidence-based dose⁽²⁸⁾. The CHAMP-HF registry demonstrated internationally that large proportion of eligible HFrEF patients were not prescribed foundational therapies and that target-dose attainment was substantially lower than treatment initiation⁽²⁸⁾. Only 1% of patients eligible for all three traditional classes in CHAMP-HF were receiving target doses of ACEI/ARB/ARNI, β-blockers and MRA simultaneously⁽²⁸⁾. Although CHAMP-HF was conducted outside India, its finding provides an important conceptual framework for interpreting Indian registry data, because the Indian gap may similarly include both prescription and dose-optimization failure⁽²⁸⁾.

The eastern Indian registry reported that four-pillar prescription increased to 76.3% by late 2024, but sacubitril/valsartan target-dose attainment remained only at 20%⁽⁹⁾. The difference demonstrates that a high prescription rate can coexist with substantial therapeutic inertia at the dose-optimization level^(9,10). Consequently, future Indian GDMT quality metrics should report at least four dimensions – i.e., initiation, number of GDMT classes, dose attainment and persistence⁽¹⁰⁾.

3.3. Association between GDMT use and clinical outcomes

Indian registry data consistently support an association between GDMT use and improved clinical outcomes^(3,7). In NHFR, HFrEF and HFmrEF patients who did not receive GDMT had higher mortality than those receiving GDMT⁽³⁾. In CSI-KHFR, the prescription of individual GDMT components were independently associated with 90-day mortality⁽⁷⁾. In the Trivandrum registry, discharge β-blocker, RAS blocker and MRA prescription were associated with lower five-year mortality risk⁽⁸⁾. These observational associations cannot establish causality, because patients receiving GDMT may differ systematically from untreated patient in disease severity, healthcare access and clinical stability⁽¹⁰⁾. However, the consistency between Indian observational evidence and randomized trials of foundational therapies strengthens the biological and clinical plausibility of the relationship^(18,19).

4. Therapeutic inertia – determinants of GDMT underuse

4.1. Definition and clinical significance

Therapeutic inertia in HFrEF can be conceptualized as failure to initiate or appropriately optimize evidence-based therapy when a patient is eligible, and no clear contraindications prevent the treatment. Therapeutic inertia should be distinguished from therapeutic intolerance because a clinically justified decision to delay or reduce therapy due to hypotension, renal dysfunction, hyperkalemia or other adverse effects is not equivalent to avoidable treatment delay⁽¹⁰⁾. Therapeutic inertia may occur at the level of treatment initiation, addition of subsequent GDMT classes, dose escalation, reinitiation after temporary interruption or continuation during follow-up. The clinical importance of therapeutic inertia lies in the cumulative exposure to preventable risk created by each delay in implementing effective therapy⁽¹⁰⁾. The 2024 HFA-ESC scientific statement identifies clinical and organizational factors as major contributors to therapeutic inertia and emphasizes structured care pathways, tailored initiation, digital interventions, education and quality registries as potential solution⁽¹⁰⁾.

4.2. Patient-related barriers

Patient-level barriers to GDMT include medication cost, limited health literacy, concerns regarding the adverse effects, polypharmacy, difficulty attending repeated follow-up visits and poor continuity after discharge⁽²⁹⁾. The financial barrier is particularly relevant in India, because heart failure treatment may require lifelong medication, repeated laboratory investigations, clinical visits and hospitalization⁽²⁷⁾. A recent multicenter Indian study reported an average annual out-of-pocket expenditure of approximately INR 106,566 among HF patients, accounting for more than 90% of total health expenditure. Major health spending was reported in 37.7% of households, while distress financing occurred in 17.7%, demonstrating the potential economic consequences of chronic heart failure management. The same study found lower major expenditure among insured patients than uninsured patients, indicating that financial protection may influence the ability to sustain long-term hart failure care⁽²⁷⁾. Medication affordability can therefore affect not only adherence but also the clinician’s willingness to prescribe therapies perceived as financially difficulty for patients to maintain^(27,29).

4.3. Physician-related barriers

Physician-related contributors to therapeutic inertia include inadequate familiarity with newer therapies, unpredictability regarding a particular sequencing, fear of hypotension or renal deterioration and reluctance to intensify the treatment in clinically complex patients⁽¹⁰⁾. Indian consensus documents specifically identify physician inertia, limited knowledge of titration and concerns regarding safety monitoring as barriers to optimal GDMT use^(16,17). Clinicians may also prioritize symptoms control with diuretics over disease-modifying therapy, because symptomatic improvement is immediate, whereas mortality and hospitalization benefits of GDMT are less immediately visible⁽¹⁰⁾. Another contributor is the tendency to wait for an ideal clinical state before initiating therapy, even though current evidence supports low-dose initiation and subsequent titration in appropriate patients⁽²²⁾.

4.4. Healthcare system-related barriers

Healthcare system barriers include fragmented post-discharge care, inadequate heart failure specialist availability, lack of dedicated HF clinics, limited laboratory access, inconsistent medication availability and inadequate systems for identifying patients who remain undertreated^(10,29). These barriers are especially relevant in India because specialist HF services are concentrated in tertiary and metropolitan centers, whereas a substantial proportion of the population lives in rural or semi-urban settings. The ICMR-NCDIR registry reported that more than 60% of participants were from rural areas, highlighting the need for treatment strategies that can function outside highly specialized urban centers⁽²⁾. In the CONNECT-HF trial, health system performance in GDMT prescription remained limited even after quality-improvement interventions, while higher performing sites were more likely to have multidisciplinary teams, including pharmacists and social workers⁽³⁰⁾. These findings indicate that therapeutic inertia cannot be corrected solely through physician education and require changes in healthcare delivery systems^(10,30).

5. Strategies to close the GDMT gap in India

5.1. Early initiation and rapid optimization

The most direct strategy for reducing therapeutic inertia is to switch from passive prescription toward a predefined initiation-and-titration pathway⁽¹⁰⁾. The STRONG-HF provides evidence that high-intensity treatment with early follow-up and rapid up-titration can improve the implementation of GDMT after acute heart failure hospitalization⁽²³⁾. The recent approach should prioritize early exposure to all four foundational classes rather than waiting for complete target dose achievement of one medication before introducing another⁽²²⁾. A practical Indian approach may therefore use a low-dose four-pillar initiation model followed by frequent assessment of blood pressure, heart rate, renal function, potassium, volume status and symptoms^(10,26). The precise order should be individualized rather than rigid, because patients with hypotension, renal dysfunction, hyperkalemia, bradycardia or persistent congestion require different implementation strategies⁽²⁶⁾. SGLT2 inhibitors are particularly attractive for early implementation, because they generally require no conventional dose titration and provide HF benefits independent of diabetes status^(18,19). Early SGLT2 inhibitor initiation following stabilization of acute heart failure is also supported by the EMPULSE trial⁽²⁴⁾.

5.2. Structured and multidisciplinary HF care

Structured heart failure clinics can convert GDMT optimization from an opportunistic process into a scheduled clinical pathway with predefined treatment targets and follow-up intervals⁽³¹⁾. An Indian randomized trial of multidisciplinary heart failure management demonstrated the feasibility of establishing a multidisciplinary HF clinic and provides direct evidence supporting structured team-based care in the Indian setting⁽³²⁾. Multidisciplinary models can incorporate cardiologists, clinical pharmacists, nurses, dietitians and other healthcare professionals according to local resources^(30,32). The HF-optimize multidisciplinary clinic increased GDMT utilization from 35.5% to 85.5% over six structured visits across 12 weeks, illustrating the potential impact of repeated medication review and active titration⁽³¹⁾. Pharmacist-led heart failure programs have similarly demonstrated improvement in GDMT optimization, supporting the incorporation of clinical pharmacy services into heart failure care pathways⁽³²⁾. Telehealth and pharmacist co-management may be particularly useful where specialist cardiology services are geographically limited. A recent pharmacist telehealth co-management study demonstrated greater achievement of three or four GDMT classes and lower cardiac hospitalization, supporting remote medication optimization as potential scalable strategy⁽³⁴⁾.

5.3. Improving adherence, affordability and access

Improving GDMT prescribing without addressing affordability produces an implementation gap between the medication prescribed and the medication actually taken⁽²⁷⁾. Generic medicines, public sector procurement and integration of essential HF medicine into reliable supply systems can potentially reduce financial barriers to treatment⁽²⁹⁾. Evidence from low-and middle-income countries demonstrates substantial variation in availability, price and affordability of heart failure medicines, indicating that medication access is a healthcare system issue rather than solely a patient adherence problem⁽²⁹⁾. Indian HF programs should therefore incorporate medication cost assessment into routine clinical review particularly for patients receiving multiple long-term therapies⁽²⁷⁾. Patient education should explain the difference between symptoms relieving medicines and disease-modifying therapies, so that patients understand the rationale for long-term GDMT continuation⁽¹⁰⁾. Simplifying dosing schedules using fixed dose combination where appropriate and providing written medication plans may further improve treatment persistence^(10,35).

5.4. Quality improvement and future research priorities

Therapeutic inertia should be incorporated into heart failure quality improvement programs as a measurable clinical performance outcome rather than treated solely as an individual clinician behavior⁽¹⁰⁾. Indian registries should routinely report the proportion receiving all four classes, dose attainment, time to initiation, time to optimization and treatment persistence^(9,10).

Future Indian studies should distinguish true contraindication from potentially modifiable treatment delay, because combining these categories can overestimate the apparent quality of prescribing⁽¹⁰⁾. Registry data should also capture socioeconomic variables, insurance status, medication cost, drug availability, distance to healthcare facilities and follow-up frequency, because these factors may explain regional differences in GDMT implementation^(27,29). Future Indian implementation trials should compare structured rapid titration programs with standard care using clinically meaningful outcomes such as four-pillar achievement, target-dose attainment, 90-day hospitalization, mortality, adherence and treatment persistence^(23,32). Pragmatic studies in tier 2, tier 3 and semi-urban hospitals are particularly important, because most existing evidence concerning rapid optimization and multidisciplinary HF care originates from specialist centers or high-income healthcare systems^(2,10).

Digital health platforms may provide a practical mechanism for monitoring blood pressure, heart rate, laboratory values, adverse effects and medication adherence between clinic visits^(36,37). Remote titration program has already demonstrated feasibility and improvements in GDMT score, suggesting potential applicability to geographically dispersed Indian population⁽³⁷⁾. Quality improvement programs should therefore move beyond measuring whether GDMT was prescribed and instead assess whether eligible patient received timely, sustained and adequately optimized treatment⁽¹⁰⁾.

6. Proposed Indian framework to close the therapeutic inertia gap

The Indian evidence supports a multilevel framework in which therapeutic inertia is addressed simultaneously at the patient, clinician, healthcare system and policy levels^(10,26). At the patient level, interventions should focus on affordability, education, adherence, early recognition of adverse effects and continuity of follow-up^(27,29). At the clinician level, simplified patient profile based on algorithms should specify when to initiate each foundational therapy, what monitoring is required, and when dose escalation should occur⁽²⁶⁾. At the healthcare system level, dedicated HF pathways should create automatic follow-up after discharge and establish responsibility for medication optimization⁽¹⁰⁾. At the policy level, strategies should address medicine affordability, insurance coverage, essential medicine availability and integration of heart failure treatment into public sector chronic disease programs^(27,29). Such a framework is particularly relevant to India, because the country’s heart failure burden spans tertiary metropolitan hospitals, district hospitals, private hospitals and resource-constrained outpatient settings⁽²⁾.

7. Conclusions

Indian registry data demonstrate a persistent gap between evidence-based recommendation and real-world implementation of GDMT in heart failure with reduced ejection fraction. The gap is evident not only in failure to prescribe individual therapies but also in incomplete four-pillar therapy, inadequate dose optimization and poor continuation after discharge. Mortality and readmission rates remain substantial in Indian HF population, with the highest risk concentrated during the early period following hospitalization. Therapeutic inertia represents an important modifiable component of this evidence practice gap, although it must be distinguished from clinically appropriate treatment limitation because of intolerance or contraindication.

The contemporary evidence supports early introduction of the four foundational GDMT classes, followed by individualized rapid optimization rather than prolonged sequential titration. Indian expert consensus has increasingly moved towards patient profile-based implementation, recognizing that treatment should be adapted according to blood pressure, renal function, potassium, heart rate, congestion and comorbidities. Multidisciplinary heart failure clinics, pharmacist involvement, structured follow-up, telehealth and quality-improvement registries offer practical approaches for translating evidence into routine care. The ultimate objective should be to replace an episodic prescribing model with a structured longitudinal GDMT pathway in which every eligible patient is systematically assessed, initiated, titrated and followed until the maximum tolerated evidence-based regimen is achieved.

Conflicts of interest: The authors declare that they have no conflicts of interest.

Acknowledgment: I sincerely acknowledge Dr. Smit Bharat Solanki for his continuous guidance, valuable support and dedicated efforts throughout the preparation of this manuscript.

Authors’ contributions: All authors have read and agreed to the published version of the manuscript.

Ethics compliance: We confirm that the article was conducted in compliance with ethical guidelines.

Funding: There was no funding for this work.