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This review serves to compare contemporary clinical practice recommendations for the management of heart failure (HF), as codified in the 2021 European Society of Cardiology (ESC) guideline, the 2022 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) guideline, and the 2023 focused update of the 2021 ESC document. Overall, these guidelines aim to solidify significant advances throughout the HF continuum since the publication of previous full guideline iterations (2013 and 2016 for the ACC/AHA and ESC, respectively). All guidelines provide new recommendations for an increasingly complex landscape of HF care, with focus on primary HF prevention, HF stages, rapid initiation and optimization of evidence-based pharmacotherapies, overlapping cardiac and noncardiac comorbidities, device-based therapies, and management pathways for special groups of patients, including those with cardiac amyloidosis. Importantly, the ACC/AHA/HFSA document features special emphasis on HF risk prediction and screening, cost/value, social determinants of health, and health care disparities. The review discusses major similarities and differences between these recent guidelines and guideline updates, as well as their potential downstream implications for clinical care., Competing Interests: Funding Support and Author Disclosures Dr DeFilippis serves on a clinical trial committee for Abiomed and has had speaker engagements with AstraZeneca. Dr Riello has served as a consultant for Alexion AstraZeneca, Boehringer Ingelheim, Janssen, Johnson & Johnson, PhaseBio, and Portola. Dr Bozkurt has received personal fees from Vifor for serving on the steering committee for the Care HF Trial; has received personal fees from Amgen, AstraZeneca, and Baxter for serving on advisory committees or for consulting outside the submitted work; has received consulting fees from Bristol Myers Squibb, scPharmaceuticals, Baxter Healthcare Corporation, Sanofi Aventis, Relypsa, and Amgen; has served on the clinical event committee for the GUIDE HF Trial sponsored by Abbott Vascular; and has served on the data safety monitoring committee of the ANTHEM trial sponsored by LivaNova. Dr Vaduganathan has received research grant support from, has served on advisory boards of, or has had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and has participated on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Despite robust evidence and strong guideline recommendations supporting use of mineralocorticoid receptor antagonists (MRAs) to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF), these medications remain underused in clinical practice., Objectives: The goal is to determine if providing a tailored best practice alert (BPA) to outpatient providers suggesting guideline-recommended MRAs or information about available hyperkalemia treatment, if present, for patients with HFrEF will increase short-term MRA prescriptions., Methods: PROMPT-MRA (Pragmatic Trial of Messaging to Providers About Treatment With Mineralocorticoid Receptor Antagonists) is a pragmatic, cluster-randomized, controlled study. A total of 119 providers were randomized to receive a BPA or usual care. During an outpatient visit with participating providers, the BPA displayed recent laboratory test values and ejection fraction. The alert suggested guideline-recommended MRAs for eligible patients with a serum potassium of <5.0 mEq/L or novel potassium binders for those with a serum potassium of ≥5.0 mEq/L, each linked to an order set containing the corresponding medication and laboratory monitoring., Results: PROMPT-MRA completed enrollment with 1,210 patients. The primary outcome of PROMPT-MRA is to determine if a tailored BPA for outpatients with HFrEF will lead to higher MRA prescriptions 6 months following randomization compared with usual care. Secondary outcomes included incidence of hyperkalemia, use of novel potassium binders, heart failure hospitalizations, and mortality., Conclusions: If effective, the BPA can be scaled to improve population health outcomes with increased MRA prescribing among eligible patients with HFrEF, with or without a history of hyperkalemia. (Pragmatic Trial of Alerts for Use of Mineralocorticoid Receptor Antagonists [PROMPT-MRA]; NCT04903717)., Competing Interests: Funding Support and Author Disclosures PROMPT-MRA (Pragmatic Trial of Alerts for Use of Mineralocorticoid Receptor Antagonists; NCT04903717) was supported by CSL Vifor. Dr Riello has participated on Advisory Boards for Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Johnson and Johnson, Medicure, PhaseBio, Portola, and Salix; honoraria and consulting fees from Alexion, Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Johnson and Johnson, Pfizer, Portola, and Salix; and stock ownership in Akebia Therapeutics, Cytokinetics, Emergent BioSolutions, Iterum, Olema Pharmaceuticals, PhaseBio, and Verve Therapeutics. Dr Ahmad has received consulting fees from Sanofi, Amgen, and Cytokinetics; and has received research funding from Boehringer Ingelheim, AstraZeneca, Cytokinetics, and Relypsa. Dr Wilson has received grants R01DK11391, R01HS027626, and P30DK079310 and research support from AstraZeneca, CSL Vifor, and WHOOP. Dr Desai has worked under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures used for public reporting and pay for performance programs; and has received research grants from and consulted for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Novartis, SCPharmaceuticals, and CSL Vifor. Drs Wilson and Desai are primary investigators of the ongoing PROMPT-MRA funded by CSL Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Acute Heart failure (AHF) is among the most frequent causes of hospitalization in the United States, contributing to substantial health care costs, morbidity, and mortality. Inpatient initiation of guideline-directed medical therapy (GDMT) is recommended for patients with heart failure with reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death or HF hospitalization. However, underutilization of GDMT prior to discharge is pervasive, representing a valuable missed opportunity to optimize evidence-based care. The PRagmatic Trial Of Messaging to Providers about Treatment of Acute Heart Failure tests the effectiveness of an electronic health record embedded clinical decision support system that informs providers during hospital management about indicated but not yet prescribed GDMT for eligible AHF patients with HFrEF. PRagmatic Trial Of Messaging to Providers about Treatment of Acute Heart Failureis an open-label, multicenter, pragmatic randomized controlled trial of 1,012 patients hospitalized with HFrEF. Eligible patients randomized to the intervention group are exposed to a tailored best practice advisory embedded within the electronic health record that alerts providers to prescribe omitted GDMT. The primary outcome is an increase in the proportion of additional GDMT medication classes prescribed at the time of discharge compared to those in the usual care arm., Competing Interests: Disclosures JH, TO, JM are employees of AstraZeneca. RJR is a consultant for Alexion, Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Johnson & Johnson, PhaseBio, and Portola. RD does executive teaching for Sanofi Consumer Health care. SEI has served on clinical trial committees and advisory boards for Boehringer Ingelheim, AstraZeneca, and Novo Nordisk. He has served as a consultant to Merck, Pfizer, Lexicon, vTv Therapeutics, Esperion and Abbott and has delivered lectures supported by Boehringer Ingelheim and AstraZeneca. TA is consultant for Sanofi-Aventis, Amgen, Cytokinetics. He has research funding from Boehringer Ingelheim, AstraZeneca, Cytokinetics, and Relypsa. NRD works under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures used for public reporting and pay for performance programs. He reports research grants and consulting for Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Novartis, SCPharmaceuticals, and Vifor. The remaining authors have nothing to disclose., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To summarize published literature on the incidence of adverse drug effects (ADEs) associated with guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF)., Study Design: Systematic literature review., Methods: A systematic literature review was conducted in PubMed, Ovid MEDLINE, and Clinical Key covering January 1990 to December 2018. Key search terms were ADEs for β-blockers (BBs), ACE inhibitors (ACEis), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), and/or angiotensin receptor-neprilysin inhibitors (ARNis) in adult patients (≥ 18 years) with HFrEF., Results: A total of 279 eligible articles were identified, of which 29 reported drug-related adverse effects and were included in this review. Of the 29 studies, 11 examined BBs; 9, MRAs; 6, ARNis; 2, ACEis; and 1, ARBs. The most common reported ADEs across these therapeutic classes included bradycardia, dizziness, hypotension, hyperkalemia, cough, and renal impairment. The incidence of BB-induced bradycardia was 1% to 52% based on 9 studies, and 6 studies described dizziness as a result of BBs and ARNis (15%-43%). Fourteen studies reported induced hypotension (1.4%-63%); 13 studies, hyperkalemia (0.6%-30.2%); 3 studies, cough (37%-50%); and 4 studies, renal impairment (0.6%-7.6%)., Conclusions: Findings show that drug-related adverse effects are commonly reported in clinical trials and highlight the sizable burden of ADEs with medical therapy across patients with HFrEF. Additional real-world evidence and studies aiming to improve the tolerability of GDMT for patients with HFrEF are warranted.