2025 HFA-ESC临床共识声明：心力衰竭时多重用药的处理

共识心血管内科· 心力衰竭 · 2025

Conclusions

The demographic changes in the HF population have introduced new important scenarios to consider when approaching the care of these patients. Polypharmacy, linked mainly with older age and multimorbidity, can negatively affect adherence to treatments, increase the risk of ADRs and drug-drug interactions, and therefore worsen patient outcomes. Although geriatricians have already integrated many strategies for the management of polypharmacy in the care of older patients in HF, and more generally in cardiology, the awareness of this problem is still limited. Moreover, in the contemporary era of HFrEF treatment, based on the four foundational GDMTs with proven survival benefit and impact on risk of rehospitalization and quality of life, polypharmacy is also extremely frequent and therefore there is need of an HF-centred approach to its management allowing to preserve HF treatments, promote their optimization and avoid their discontinuation. This entire process should incorporate a multifaceted approach balancing non-adherence and clinical inertia against a rational approach to polypharmacy, with prioritization of treatments with strong evidence of efficacy and safety, and therefore requires the involvement of different healthcare providers and specialties, the integration of regular care with technologies and with industries, and can be facilitated by educational programmes for patients, family specialists and general practitioners.

Conflict of interest: D.S. has received honoraria for lectures and fees for expert advice from AstraZeneca, Novo Nordisk, Novartis, Janssen, Dompè, Boehringer Ingelheim and Merck; all unrelated to the current article. M.I. reports consultancy, speaker's fees from AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Abbvie, Neopharmed-Gentili, Novo Nordisk, Medtronic; payment for writing manuscript: Boehringer Ingelheim. O.C. has received grants from Servier. M.S.A. has received personal fees from Servier. A.B.G. has lectured and/or participated in advisory boards for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Novo Nordisk, Roche Diagnostics, Vifor. F.B. is consultant for Medtronic and Biotronik and has received speaker fees from Biosense Webster, Biotronik, Boston Scientific, Abbott, Pfizer, Novartis, Amgen and Orion. G.F. reports lecture fees and/or committee member contributions in trials sponsored by Bayer, Medtronic, Vifor, Servier, Novartis, Amgen, and Boehringer Ingelheim; and research support from the European Union. P.J. has received speaker fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, Sun Pharmaceuticals, and Intas Pharmaceuticals; has received advisory board fees from AstraZeneca, Boehringer Ingelheim, and Novartis; has received research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices Inc; his employer the University of Glasgow has been remunerated for clinical trial work from AstraZeneca, Bayer AG, Novartis, and Novo Nordisk; and is the Director of Global Clinical Trial Partners (GCTP); he is supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund. A. ubmitted work. All the other authors have nothing to disclose.

|Reduce amiodarone dose, monitor digoxin concentration,|prefer non-pharmacological interventions||Use the minimal effective dose, educate patients to|avoid/control postural hypotension, use alternative drugs|without action on blood pressure/heart rate (i.e.|trimetazidine, ranolazine)|Collaborate with oncologist; monitor for cardiotoxicity during|treatment|Patients with HFrEF and COPD benefit from beta-blockers; use|cardioselective beta-blockers; monitor respiratory function|and symptoms closely|Regularly monitor renal function; consider alternative|medications|Involve caregivers and specific professional figures in daily|patient care (e.g. HF nurse); simplify the regimen and|consider longer-acting formulations to reduce dosing|frequency|Avoid PDE5-i in association with nitrates or vericiguat, prefer|5-alpha reductase inhibitors for BPH, implement|antihypertensive in women on oestrogen replacement|therapy|Prioritize HFrEF GDMT as antihypertensive drugs, consider|single-pill combination|Choose antibiotics with minimal cardiac adverse effects;|monitor for interactions|Coordinate care between cardiologist and endocrinologist;|adjust medications|Use acetaminophen or non-pharmacological pain management;|monitor for fluid retention||Collaborate with psychiatrist; consider non-interfering|psychiatric medications; monitor ECG for QTc interval|Non-pharmacological approaches for sleep; cautious use of|sedatives|Adjust cardiac medications based on thyroid function; regular|monitoring| |---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

|Amiodarone and digoxin can cause hypokinetic|arrhythmias in association with beta-blockers||Long-acting nitrates may cause postural hypotension|when associated with other vasodilators|||Some cancer treatments may adversely affect cardiac|function and interact with medications|Beta-blockers may exacerbate COPD symptoms;|consider cardioselective agents||Adjust drug dosages based on renal function; avoid|nephrotoxic agents|Risk of adverse effects and drug interactions||||Risk of adverse effects, hypotension, GDMT dose|reduction or discontinuation|||Hypotension, adverse effects, drug accumulation and|interactions, GDMT de-escalation/withdrawal|Some antibiotics may interact with cardiac|medications; monitor for side effects|Some metabolic medications may have CV effects;|monitor glucose levels|NSAIDs can interact with diuretics and ACE inhibitors;|Cox-2 inhibitor associated with higher rate of CV|events; consider alternative pain management|Antidepressants may interact with beta-blockers;|monitor for mood changes and sodium level|Sedatives may exacerbate HF symptoms; monitor for|respiratory depression|Thyroid hormones may impact CV function; monitor|thyroid levels|

|Anticoagulants may increase bleeding risk,|hypokinetic arrhythmias secondary to|rate/rhythm control treatments|Antiplatelets may increase bleeding risk, antianginal|treatments can induce bradycardia/hypotension|||Potential for drug interactions with chemotherapy|agents|COPD exacerbation, potential for drug|interactions with bronchodilators||Reduced renal function may impact drug clearance,|potential for drug accumulation and toxicity|Difficulty managing complex medication regimens||||Drug interactions with treatment for ED,|hypotension with alpha-blockers, worsening|hypertension with oestrogen replacement|therapy|Postural hypotension, worsening renal function||Potential for drug interactions with antibiotics,|especially fluoroquinolones and antivirals|Potential for drug interactions with antidiabetic|agents|NSAIDs may exacerbate HF symptoms|||Potential for drug interactions with psychotropic|and nootropic medications|Potential for drug interactions with sedatives and|hypnotics|Altered metabolism and potential for drug|interactions|

||||CAD||||Cancer||COPD|||CKD||Dementia/cognitive|impairment|||Gender-specific|pathologies|||Hypertension||Infections||Metabolic disorders||Osteoarthritis|||Mental disorders||Sleeping disorders||Thyroid disorders||

|Beers criteria 91|List of:|• Multiple updates| |---|---|---|

||• Specific drug-drug interactions • Potential inappropriate medications|• Promoted by the American Geriatrics Society • Regularly updated|

||• Medications to avoid in certain conditions||

||• Medications to use with caution||

||• Medications needing dose adjustment in renal||

||dysfunction||

|STOPP/START criteria|||

EN_PAPER

How to handle polypharmacy in heart failure. A clinical consensus statement of the Heart Failure Association of the ESC

Authors

Keywords

Adherence, Comorbidities, Heart failure, Polypharmacy

Abstract

The multiplicity of coexisting comorbidities affecting patients with heart failure (HF), together with the availability of multiple treatments improving prognosis in HF with reduced ejection fraction, has led to an increase in the number of prescribed medications to each patient. Polypharmacy is defined as the regular use of multiple medications, and over the last years has become an emerging aspect of HF care, particularly in older and frailer patients who are more frequently on multiple treatments, and are therefore more likely exposed to tolerability issues, drug-drug interactions and practical difficulties in management. Polypharmacy negatively affects adherence to treatment, and is associated with a higher risk of adverse drug reactions, impaired quality of life, more hospitalizations and worse prognosis. It is important to adopt and implement strategies for the management of polypharmacy from other medical disciplines, including medication reconciliation, therapeutic revision and treatment prioritization. It is also essential to develop new HF-specific strategies, with the primary goal of avoiding the use of redundant treatments, minimizing adverse drug reactions and interactions, and finally improving adherence. This clinical consensus statement document from the Heart Failure Association of the European Society of Cardiology proposes a rationale, pragmatic and multidisciplinary approach to drug prescription in the current era of multimorbidity and 'multi-medication' in HF.

Introduction

7] [8] [9] Most patients with HF have ≥3 coexisting comorbidities, with the burden of cardiovascular (CV) and non-CV comorbidities rising over time. 10 This has direct consequences in terms of number of concomitant prescribed medications, and therefore polypharmacy (i.e. 2] [13] [14] [15] [16] Notably, in patients with HF with reduced ejection fraction (HFrEF), the use of guideline-directed medical therapy (GDMT) consists of ≥4 drugs, which further contributes to the pill burden. 2 This scientific statement document from the Heart Failure Association of the European Society of Cardiology (ESC) aims to provide advice on how to optimize the use of polypharmacy in the context of HF management, and to propose a rational, pragmatic and multidisciplinary approach to drug prescription in the current era of multimorbidity and 'multi-medication' in HF.

Polypharmacy in heart failure: definition and epidemiology

Polypharmacy is broadly defined as the regular use of multiple medications, and has been classified as the chronic use of ≥5 medications, while hyper-polypharmacy refers to the use of ≥10 medications. 17 However, in patients with HFrEF requiring four medications (plus eventual loop diuretics), which represents the foundational GDMT, polypharmacy is almost the rule if this standard definition is applied. 2 The proportion of HF patients taking ≥10 drugs ranges between 25% and 50%. 18, 19 Therefore, the focus should be on the appropriateness of medications rather than simply the number of medications when defining polypharmacy in HF. 11 Polypharmacy is associated with the underuse of GDMT in HF, and patients with HFrEF who are on multiple non-CV medications have lower odds of achieving optimal medical treatment for HF. 20 olypharmacy increases the risk of non-adherence and adverse drug reactions (ADRs) and drug-disease interaction, and also contribute to increased healthcare costs. 21 y points:

• Polypharmacy is classified as the daily use of ≥5 medications.

• Hyper-polypharmacy refers to ≥10 medications.

• The standard definition of polypharmacy (i.e. chronic use of ≥5 drugs) is almost the rule in patients with HFrEF on foundational quadruple therapy. • In patients on polypharmacy, the focus of the management should be on the appropriateness of prescriptions rather than on an arbitrary number of drugs.

Strategies to manage polypharmacy and reduce burden pill

Prioritizing the treatment of comorbidities by using heart failure guideline-directed medical therapy

In the setting of specific comorbidities, use of treatments with multiple indications (including HF) can be prioritized to reduce burden pill. In patients with HFrEF and atrial fibrillation, beta-blockers should be prioritized for rate control as already indicated for the treatment of HF, 2 whereas due to the increasing evidence supporting the prognostic benefit of catheter ablation in HF, interventional strategies could represent a valid option to be discussed within the multidisciplinary team and with the patient. 22, 23 eta-blockers can be prioritized for the relief of angina in chronic coronary syndromes if HF coexists. 24 ntihypertensive treatments with strong evidence for the treatment of HFrEF, but also with less strong evidence when the ejection fraction phenotype is preserved or mildly reduced, should be prioritized and optimized over other antihypertensive treatments.

] [28] Chronic kidney disease is a frequent real or perceived barrier to the optimization of HF GDMT, but GDMT has evidence of benefit and safety also in patients with chronic kidney disease up to stage 3b/4, 29 and therefore during the processes of therapeutic revision and reassessment of treatments appropriateness these drugs should be continued unless contraindicated.

Key points:

• Prioritize the use of treatments with multiple indications (including HF) to reduce burden pill, when multiple comorbidities coexist. • Deprescribing/discontinuation of GDMT should be avoided in absence of clear contraindications.

Therapeutic competition and priority in polypharmacy

Therapeutic competition is defined as a clinical situation where a medication that treats one condition is harmful to another, introducing the complex issue of treatment prioritization. Competing health priorities complicate treatment optimization in patients with HF, especially in older adults, leading to the need of developing evidence-based patient-centred strategies for managing patients with polypharmacy. 30 rug prescribing usually follows a disease-specific approach based on guideline recommendations. By focusing on the direct relationship between a specific drug and a disease, without considering the patient's overall health, polypharmacy can be used inappropriately. This approach leads to fragmented care rather than promoting a holistic, person-centred treatment plan, which is particularly an issue in HF given the frequent coexistence of CV and non-CV comorbidities leading to likely polypharmacy. 11 Patient's characterization is key to achieve proper treatment prioritization. The presence, number and severity of comorbidities should be carefully evaluated, as well as their impact on life expectancy. For instance, HF and cancer are diseases strongly affecting patient's prognosis. Therefore, it becomes a primary goal to keep patients on these treatments, while eventually reconsidering those for other non-life-limiting conditions. This is even more valuable for younger patients with longer life expectancy.

Decisions on treatment selection should take into consideration that older patients with HF often contend with physical and functional limitations that span multiple domains: medical (HF-related), cognitive, physical and socio-economical. 31 Age alone should not be intended as a barrier to treatment initiation; however, if a patient presents overt deficits in one or more of these domains, the aim should be achieving the best balance between the need of GDMT optimization and potential safety, tolerability and adherence issues. Self-reported health status and quality of life are also important aspects to be discussed with patients, and the aim should be finding the optimal compromise between the implementation of evidence-based treatments, therapeutic adherence and quality of life. 11 The further step is the definition of therapeutic goals, which is influenced by the comorbidities that might affect life expectancy and, in the more advanced disease stages, by the presence of frailty or the need for palliative care. In older patients with HF, who may not have longer survival as the primary goal but rather quality of life, treatment should be redefined accordingly. However, given the unquestionable benefit in quality of life achieved with HF GDMT, 32 its implementation maintains a solid basis also in these patients. The entire process of prioritization should be therefore shared across all the specialists involved in the patient care.

• Decisions on treatment prioritization should follow a patient-centred approach with main focus on the patient's overall health. • This comprehensive patient-centred assessment should consider physical and functional limitations, the co-existence of comorbidities and related treatments, and the presence of socioeconomic barriers. • The final goal is the identification of the best balance between GDMT optimization, safety, tolerance, adherence, and quality of life.

Revision of therapy: deprescribing

Drug-drug interactions as well drug-disease interactions, and other drug-related specific issues, are very common when patients are prescribed multiple treatments (Table 1 ). Inappropriate prescribing warrants careful consideration by specialists and requires timely review for each patient during every medical encounter. Several medications may cause or exacerbate HF, and should therefore represent the first-choice targets for deprescribing. 33 owever, in daily clinical practice, such drugs are often not discontinued at discharge in patients hospitalized for HF. 34 The use of over-the-counter (OTC) products and the access to self-care medications are also extremely frequent in the HF population and contribute to polypharmacy. 35, 36 Eighty-eight percent of HF patients use products not requiring any prescription, 37 and this is also often not reported by the patient to the treating physicians. 38 he core principle of prescribing medications only when the potential benefits exceed the risks has recently been complemented by a paradigm shift towards proactive deprescribing when the harms outweigh the benefits. 11, 39 comprehensive definition of deprescribing should include: (1) a structured process of medication withdrawal, especially of inappropriate and unnecessary medications, or dose reduction;

(2) oversight of the deprescribing process by a member of the healthcare team; (3) the goal of improving one or more specific outcomes (e.g. mortality, morbidity, quality of life, disease relapse); and (4) consideration of the patient's overall physiological status, stage of life, and goals of care. 40 2025 The Author(s). welve reported sections (CV system, coagulation system, central nervous system, renal system, gastrointestinal system, respiratory system, musculoskeletal system, urogenital system, endocrine system, falls risk increasing drugs, analgesic drugs, vaccines) with criteria to start and stop medications Ten questions to be addressed for potential drug-related problems associated with a specific medication (degree 1 to 3)

• Assessment of a range of issues relevant for a variety of medications PRISCUS and PRISCUS 2.0 criteria 94, 95 List of potentially inappropriate medications for older patients, possible alternative drugs, and precautions if cannot be avoided.

• Based on a consensus panel (Delphi method) in Germany and focused on German pharmaceutical market French consensus panel 96 List of potentially inappropriate medications. List of criteria with reasons for concern and possible alternative drugs Disagreement in reported drug treatments across different healthcare providers (e.g. patients, specialists, general practitioners, etc.) can be frequent. The process of deprescribing starts with a careful revision of patient's therapies, including self-prescribed and OTC medications, in order to identify the most accurate list of all the ongoing treatments. This process is called medication reconciliation and consists in comparing the medical record to an external list of medications obtained from a patient, hospital, or other provider. 41 It should involve a collaborative decision-making between different healthcare providers, patients, and sometimes caregivers or family members. The aim is avoiding therapeutic mistakes such as omissions, duplicates, dosing errors, or drug interactions. 42 4] [45] However, none of these tools has been specifically designed for HF, which must be carefully considered when they are applied to patients with HF, otherwise the potential risk is to deprescribe HF GDMT. Dedicated tools for the management of polypharmacy in HF are therefore strongly advocated.

. Polypharmacy stewardship is a relatively novel concept aiming at integrating all the processes of medication revision and deprescribing, to promote the appropriate use of drugs and minimize medication-related harm. It is defined as a coordinated intervention designed to assess, monitor, improve, and measure the pharmacological treatment of multimorbidity, taking into account the use of potentially inappropriate medications, potential prescribing omissions, drug-drug and drug-disease interactions, and prescribing cascades (i.e. initiation of a new medicine to 'treat' an ADR associated with another medicine), 46 with the aim of aligning treatment regimens with the overall condition, prognosis, and preferences of the individual patient. 44 The medication steward is a skilled and experienced pharmacist who is expected to review medications in order to identify possible opportunities for deprescribing of non-essential drugs contributing to the high drug burden index score.

In this scientific statement document, we propose a deprescribing protocol including five steps (Figure 1 ): 1. To review and reconcile all drugs the patient is currently taking, the underlying indications and whether there is current or past history of non-adherence. 2. To consider the risk of drug-induced harm in individual patients: medication-related factors to consider include known ADRs, drug-drug or drug-disease interactions, and polypharmacy. 3. To assess each drug regarding its current or future expected benefit or harm, or the likelihood of being particularly burdensome (i.e. for instance big tablets difficult to swallow, treatments needing repetitive monitoring, etc.). 4. To prioritize for discontinuation drugs that have the lowest benefit-harm ratio, the lowest likelihood of adverse withdrawal reactions or disease rebound syndromes, and are easy to withdraw. Attention should be paid to patient preferences. 5. To implement a discontinuation regimen and closely monitor patients to early identify the results of the intervention. Slow tapering over time may be required for some agents associated with increased risk for an adverse drug withdrawal event. These events may include a relapse of symptoms as a result of the withdrawal, or a physiological withdrawal such as rebound tachycardia after discontinuation of beta-blockers or an increase in blood pressure after discontinuation of anti-hypertensive agents. 47 Practical application of these recommendations can be apparently difficult and not immediate in routine care.

Responsibility of therapy revision should not belong to one specific healthcare provider. Multidisciplinary discussion and mutual support in the decision-making and in the process of deprescribing are priorities. Together with the HF physician in charge, specialized HF nurses and pharmacists are of value in the management of every step of this process.

The rationale for drug discontinuation is inadequately addressed by randomized controlled trials (RCTs) and is not explored in the guidelines. 48 There are various barriers to deprescribing which can involve the healthcare system, physicians and patients. 49 There is no consensus nor solid evidence regarding the most appropriate approach to deprescribing in multimorbid HF patients. Patients may perceive deprescribing as a form of abandonment of care or a . Patients may be hesitant to discontinue a medication initiated by other physicians, and there is often a lack of proactive communication between healthcare professionals and patients regarding the rationale for deprescribing a specific treatment. Healthcare-related barriers to deprescribing may include the lack of dedicated time, lack of adequate staffing, lack of a consistent deprescribing workflow, and limited documentation in the medical records of patients.

• Dedicated time to the careful revision of prescriptions at every medical encounter can contribute to avoid inappropriate prescribing. • Deprescribing aims to reduce unnecessary or potentially harmful medication use in order to improve patient outcome. • Several tools are available to address polypharmacy in the elderly population (Table 2 ). • Deprescribing should follow a structured stepwise process (Figure 1 ). • Multidisciplinary discussion is key to the practical process of deprescribing.

Fixed-dose combination in heart failure

3] [54] [55] Such a strategy improves patient adherence, and can aid in mitigating the polypharmacy burden. In patients with systemic hypertension, FDC reduced the daily pills intake, has been found to increase patient adherence, and is currently recommended as initial strategy for most patients. 50, 56, 57 Exceptions are patients with moderate-to-severe frailty, symptomatic orthostatic hypotension, or older people (aged ≥85 years). 57 ata from a meta-analysis confirmed the positive impact of FDC on CV outcomes in primary prevention. 58 In patients with recent myocardial infarction, a polypill including key medications (aspirin, angiotensin-converting enzyme inhibitor, statin) reduced CV events by 24% as compared with usual care, and European guidelines on hypertension support the use of FDC for primary and secondary prevention of CV outcomes. 57, 59 n HFrEF, the strong recommendation by ESC guidelines on HF supporting an early initiation of the four foundational classes of drugs with evidence-proved benefit on mortality/morbidity might encourage the development of a FDC in order to simplify the treatment schedule and to reinforce patient adherence. 2 Estimated eligibility for FDC and improved adherence in HFrEF are high. 60 owever, no RCTs have specifically assessed the efficacy and more importantly the safety of FDC in HF. There are specific issues in the HFrEF treatment implementation that might represent an obstacle to FDC strategies: (1) three out of four HFrEF drugs require dose up-titration, (2) tolerated doses can be lower than the 100% target dose for one or more HFrEF drugs, (3) disease status (symptoms, blood pressure, heart rate, haemodynamic stability, etc.) is dynamic in HF and influences the maximally tolerated doses over time, and (4) in the case of ADRs or other tolerability issues, the identification of the implicated drug can be difficult. For all these reasons, FDC in HFrEF might be more appropriate for therapeutic maintenance rather than for the implementation phase. Once the patient has achieved the maximally tolerated dose and demonstrated disease stability, this approach could simplify medication self-management and reduce the daily pill burden. Two ongoing open-label RCTs are testing the FDC of GDMT therapies in patients with HFrEF (NCT04633005, NCT06029712). 61

• Single-pill combination of antihypertensive agents is recommended to reduce the daily pills burden. • FDC can improve patient adherence and mitigate polypharmacy.

Digital health and remote monitoring

Digital systems might offer valuable solutions to optimize treatments and better manage polypharmacy. Over the last decades, with the aid of e-prescription, several computerized prescription support systems (CPSS) or computerized clinical decision support systems (CDSS) have been developed to reduce overdosing of drugs, medication errors, drug-drug interactions and the number of inappropriate prescriptions, 62, 63 by assisting physicians in drug selection and dosing, flagging potential ADRs and drug allergies, and identifying duplication of therapy. 64, 65 CPSS and CDSS can be differently applied to electronic health records at hospital institutions or in primary care. Alternatively, direct contact with patients through different virtual healthcare solutions can also represent valid strategies for therapeutic monitoring and implementation. 66, 67 n the in-hospital setting, virtual care-guided strategies of implementation were demonstrated to be safe and to improve GDMT in patients with HFrEF admitted for HF but also for . 9] [70] The results available for CPSS supporting the prescription of pharmacological treatments are contradictory.

There is a wide heterogeneity across the studies on the topic including differences in operative systems, modalities of integration of digital data in clinical records or the interaction with artificial intelligence technologies. 71 Moreover, remote patient monitoring with wearable devices can assist physicians and allow a prompt identification of potentially harmful situations linked with multiple drug administration (e.g. hypotension, low heart rate, etc.) along with early detection of worsening HF. 72 Telemedicine or more simply phone interviews can also support patients with managing their daily medication regimens, thus improving adherence. [75] Key points:

• Digital systems can support physicians in proper drug prescription, ADRs and drug-drug interactions monitoring, identification of inappropriate treatments and allergies, selection of better drugs and dosing. • In-hospital virtual care-guided strategies of implementation are safe and can improve the implementation of GDMT. • Remote patient monitoring can contribute to guide treatment implementation and to the early identification of harmful conditions linked with polypharmacy.

Linking implementation science with polypharmacy management

The uptake of life-prolonging GDMT for HF remains slow in clinical practice, 76 and the availability of additional evidence-based drugs for HFrEF may apparently contrast with the need of avoiding polypharmacy particularly in older people, which vice versa can affect GDMT optimization. 20 Clinicians are encouraged to use individualized risk-benefit assessments for therapeutic decisions. However, growing evidence suggests that alternative strategies and collaboration with other healthcare professionals can also effectively achieve optimal outcomes for patients. Although several studies have explored the effect of implementation strategies to improve the uptake of GDMT for HF, 36, 69, [77] [78] [79] [80] the effects of interventions aiming at reducing the overall pill burden, for instance by critical review of the number and appropriateness of concomitant non-HF treatments, have not been investigated. The PHARM-CHF study assessed the effect of an interdisciplinary intervention involving the local pharmacy on medication adherence in patients with chronic HF. It consisted of a two-step approach: first, medication review and generation of a medication plan, and second, preparation of a weekly dosing aid. The pharmacy-care approach improved medication adherence, but no information was provided on impact of the medication review on the total number of medications. 36 ince it demonstrated to enhance the adherence to prescribed treatments with an improvement in quality of life, a dedicated study investigating the advantage obtained with this approach in terms of © 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

overall pill burden and reduction in adverse effects might be a reasonable option to provide an evidence-based approach to polypharmacy. 81 An alternative strategy consisting of algorithm-based recommendations developed by a virtual care team (i.e. centralized physician, study staff, and local pharmacist) was also effective at improving treatment implementation, but still there was no specific focus on issues related with polypharmacy. 69 On the other hand, in the PAL-HF trial enrolling patients with advanced HF, palliative care failed to reduce medication counts in a setting where deprescribing unnecessary medications might significantly impact the quality of life in patients with end-stage HF. 82 In the more general setting of older adults with polypharmacy, deprescribing strategies are apparently safe. A review of 14 RCTs including patients aged 65 years or older in primary care or outpatient sites, community pharmacies, hospital or nursing home/long-term care facilities, tested several different types of interventions in terms of settings and preparation, use of different interdisciplinary teams, validated guidelines and tools, patient-centredness and implementation strategy. It confirmed the safety of deprescribing, the effectiveness in reducing the number of medications and suggested a potential positive effect on quality of life. 83 Few RCTs specifically focused on the safety of deprescribing CV medications in particular subsets of patients, apparently with positive results in terms of safety. 40, 84 With the exception of the TRED-HF study, which was designed to address a different aim (i.e. evaluating the risk of relapsing dilated cardiomyopathy HF after withdrawal of GDMT in patients with recovered ejection fraction), no dedicated RCTs on polypharmacy management in patients with HF are currently available. 40, 84 et, such trials on therapeutic revision in the setting of HF, with specific attention to older and frail patients, are strongly needed to define the best strategy to achieve the combined goal of GDMT implementation and management of polypharmacy while ensuring patient adherence. As the burden of non-CV polypharmacy has demonstrated to negatively affect the likelihood of GDMT initiation and optimization, 85 appropriate deprescribing of redundant treatments might facilitate a better implementation of HF medications (Graphical Abstract).

• Decision-making on therapeutic revision should follow an individualized risk-benefit assessment. • Adherence to HF GDMT can be improved by implementation strategies; however, integrating critical and systematic review of the non-HF treatments might also contribute to reduce the burden pill, leading to better GDMT. • Interdisciplinary interventions and multidisciplinary teams are strongly advised to simultaneously promote HF GDMT optimization and the management of polypharmacy in order to support patient adherence.

Polypharmacy from the patient perspective

Strategies to improve the organization of medication, for example, by using pill organizers, updated printed lists providing the medication schedule with track changes as well as established procedures for taking the prescribed drugs as part of daily routines are essential for promoting a safe and effective medication use.

• Daily self-management of multiple treatments has strong psychological implications which, in turn, can contribute to non-adherence. • Complete and clear communication with patients and caregivers on all the aspects related with prescribed treatment is mandatory and their complete understanding should be verified. • Patient education and active involvement of patients in their care can contribute to improve adherence and reduce the issues related with polypharmacy.

A.M. has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and MSD; is a consultant for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and is coinventor of a patent on combination therapy for patients having acute or persistent dyspnoea. M.P. reports consultancy, speaker's fees from AstraZeneca, Boehringer Ingelheim, Novo Nordisk; payment for writing or reviewing the manuscript: Menarini, Servier. R.R. has received lecturer fees from Pfizer and AstraZeneca and has participated in advisory boards for Pharmacosmos. P.S. has received consultancy agreement and honorarium for lecture from Boehringer Ingelheim, Novartis, AstraZeneca Menarini and Roche Diagnostics. M.S. reports honoraria from Alnylam, AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Pharmacosmos, Vifor Pharma; consultancy from Novartis, Bayer, Boehringer Ingelheim, LumiraDx, Roche Diagnostics; and support to attend educational events from Novartis, Pharmacosmos. H. H.S. received honorarium as speaker from Boehringer, Novartis, Abbott, AstraZeneca, Servier, Vifor and Pfizer. C.G.T. has received honoraria or consultation fees from Viva-Lyfe, Univers Formazione, Solaris, Summeet, AstraZeneca, Medtronic and Myocardial Solutions, and funding from Amgen and MSD, outside the submitted work, and is listed as an inventor of 2 patents related to heart failure. B.S.L. reports consulting fees from Janssen R & D and Idorsia. M.M. has received consulting fees from Abbott Vascular, Actelion, Amgen, AstraZeneca, Bayer, Edwards Therapeutics, Livanova, Servier, Vifor Pharma, and WindTree Therapeutics. G.M.C.R. reports speaker fees/consultancies from AstraZeneca, Boehringer Ingelheim, CSL Vifor, Alnylam, Servier, Medtronic and Menarini. G.S. reports grants and personal fees from Vifor, Boehringer Ingelheim, AstraZeneca, Novartis, Cytokinetics, Medtronic, Bayer, Pharmacosmos, personal fees from Servier, Abbott, TEVA, INTAS, Edwards Lifesciences, grants from Boston Scientific, Merck outside the submitted work. All the other authors have nothing to disclose.

References

引用 / 出处

2025 HFA-ESC临床共识声明：心力衰竭时多重用药的处理. 2025.