Beyond Prescribing: Strengthening Nurse-Led Implementation of Guideline-Directed Medical Therapy in Heart Failure Care

Dear Editor, The management of heart failure has evolved substantially with the emergence of Guideline-Directed Medical Therapy (GDMT), which has significantly changed the management of heart failure in patients with reduced ejection fraction (HFrEF). The combination of therapies such as angiotensin receptor-neprilysin inhibitors, evidence-based β-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors has considerably improved therapeutic options for patients with HFrEF. [1,2] Despite these advancements, many eligible patients receive suboptimal treatment or fail to achieve guideline-recommended target doses. [2–4] The key challenge in contemporary practice is translating established evidence into routine clinical practice. Delayed initiation of treatment, insufficient up-titration, concerns regarding adverse effects, inadequate follow-up, and fragmented care continue to hinder GDMT implementation.[2,3] Such challenges may be higher in low- and middle-income countries (LMICs), where healthcare professionals and resources are constrained.[5,6] Indian studies have reported low GDMT utilisation among patients with HFrEF,[5,6] while a quality-improvement intervention in South India has observed that structured implementation strategies could improve GDMT prescription at discharge.[7] To reduce this practice gap, a multidisciplinary approach is needed in which nurses play an expanded role in THE implementation of GDMT. Their contribution across hospitalisation, discharge planning, follow-up, rehabilitation, and patient education provides opportunities for medication reconciliation, adherence support, symptom monitoring, and timely identification of treatment-related adverse effects. [2-9] Nurse-led models have shown the feasibility of protocol-driven pharmacological up-titration, [8,9] but the level of nursing autonomy and prescribing authority varies across healthcare systems. Therefore, nurse-led GDMT should complement, rather than replace, physician-led care and should operate within clearly defined protocols and escalation pathways. Evidence supports the potential of nurse-led approaches to improve medication optimisation and patient outcomes. A systematic review and meta-analysis found improved initiation and up-titration of guideline-directed therapies with nurse- and pharmacist-led interventions.[2] However, its mortality analysis did not show a statistically significant reduction (RR 0.82, 95% CI 0.67-1.04), indicating uncertainty regarding a mortality benefit. [2] A meta-analysis of randomised trials subsequently reported lower all-cause rehospitalisation, heart-failure rehospitalisation, and all-cause mortality with intensive nurse-led medication optimisation.[10] The difference in mortality estimates between these meta-analyses should therefore be interpreted cautiously, given differences in included interventions, populations, follow-up periods, and study designs. Moreover, safety reporting was limited in the trials included in the latter meta-analysis, with adverse events reported by only a small number of studies. [10] Nurse-led up-titration has also been associated with improved beta-blocker optimisation. [9] In contrast, specialised nurse-led pharmacological up-titration was associated with improved left ventricular ejection fraction.[8] The latter evidence came from a retrospective longitudinal cohort of 378 patients with newly diagnosed HFrEF managed in a specialised nurse-led clinic without a usual care control group; therefore, the observed improvement in LVEF cannot be attributed solely to nurse-led titration. [8] Earlier evidence demonstrated benefits of nurse-led heart failure clinics in survival and self-care behaviour.[11] This study included 106 patients and predates the contemporary four-pillar GDMT era; therefore, its findings provide historical evidence for nurse-led heart failure but have limited direct applicability to current four-pillar GDMT optimisation. [11] More recently, a multicentre Australian real-world cohort of 2004 patients showed substantial improvement in four-pillar GDMT uptake following nurse-led remote optimisation, highlighting the potential scalability of remote models.[3] Because the Australian programme used a single-arm pre-post design without a concurrent control group, the observed changes cannot be attributed exclusively to the intervention. [3] An Indian randomised trial further identified benefits of nurse-led cardiac rehabilitation on quality of life and biophysiological parameters. Importantly, this Indian study evaluated nurse-led cardiac rehabilitation rather than protocol-based GDMT titration and therefore should not be integrated as titration-related evidence for nurse-led GDMT optimisation. [12] To our knowledge, published evidence specifically evaluating nurse-led protocol-based GDMT titration in LMICs remains limited, and we did not identify a published LMIC trial directly testing such a model. The available Indian evidence has instead focused on GDMT utilisation, quality-improvement strategies or nurse-led cardiac rehabilitation. [5-7,12] This distinction is important because evidence generated in high-income healthcare systems may not be directly transferable to LMIC settings with different workforce structures, regulatory frameworks, access to laboratory monitoring and healthcare resources. Safety is also an important consideration when expanding nurse-led GDMT optimisation. In the STRONG -HF trial, rapid up-titration was associated with a higher frequency of adverse events than usual care, although serious and fatal adverse events were similar between groups.[1] Close follow-up with usual care was observed to be similar between groups. This increased adverse event burden included clinically relevant concerns such as hypotension, renal impairment, hyperkalaemia and bradycardia; in contrast, safety outcomes were sparsely reported across the randomised trials included in the nurse-led optimisation meta-analysis. [10] Nurse-led GDMT models should therefore incorporate structured monitoring of blood pressure, heart rate, and renal function, together with predefined criteria for dose modification, temporary withholding of therapy and physician escalation. Despite this evidence, implementation still faces various barriers, including limited prescribing authority, legal and regulatory restrictions, physician-centric work cultures, workforce shortage, workload-related constraints, inadequate and less frequent training, along with lack of well-formulated and standardised titration protocols. These barriers are mainly relevant in resource-constrained settings. [5,6] Successful implementation of this approach therefore requires clearly defined professional roles; physician-nurse collaboration; institutional support; adequate staffing; and standardised protocols. In India, Nurse-led GDMT implementation should remain within recognised nursing scopes of practice, institutional policies and physician- supervised protocols. The Indian Nursing Council’s NPCC framework supports advanced nursing responsibilities within institutional protocol but should not be interpreted as unrestricted prescribing authority. Locally approved delegation and escalation pathways are therefore essential. Professional training should also include GDMT principles, medication titration, laboratory monitoring, adverse-effect recognition, patient counselling, and escalation criteria. Competency-based education and supervised implementation may improve consistency and patient safety. Digital health technologies may extend nurse-led GDMT beyond traditional outpatient settings through telehealth, remote monitoring, electronic medication tracking, and clinical decision-support systems. Evidence from Australian research SUPPORTS the feasibility of nurse-led remote optimisation at scale.[3] Yet, connectivity, digital literacy, privacy, and existing workforce capacity should be considered when implementing similar models. Implementation science can further support these approaches by clarifying the mechanisms and contextual factors that influence the integration of nurse-led GDMT into routine care. The Consolidated Framework for Implementation Research (CFIR) can help to identify organisational, individual, intervention-related, and contextual determinants used to assess reach, adoption, implementation, and maintenance. The RE-AIM framework can be used to assess reach, effectiveness, adoption, implementation, and maintenance of nurse-led GDMT intervention. In low- and middle-income countries, assessment of health-system readiness, fidelity, sustainability, and scalability is a key consideration. Future studies should investigate nurse-led GDMT optimisation in heart failure clinics, protocol-directed titration, telehealth, remote monitoring, and multidisciplinary models, with attention to clinical outcomes as well as feasibility, cost, workload, fidelity, and sustainability. Adequately powered controlled studies in LMICs, particularly India, are needed to establish the effectiveness and appropriate level of nursing autonomy and supervision. The future of heart failure management will rely not only on developing novel therapies but also on ensuring that existing evidence-based therapies reach every eligible patient at the appropriate time. Strengthening the role of nurses as implementation partners, along with standardised dose and delivery protocols, competency-based training, multidisciplinary collaboration, digital infrastructure, and implementation-focused research, may help narrow the persistent gap between evidence and practice, particularly in LMICs. Conflict of Interest: None. Financial support and sponsorship: None.