Society Guidelines
CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction

https://doi.org/10.1016/j.cjca.2021.01.017Get rights and content

Abstract

In this update of the Canadian Cardiovascular Society heart failure (HF) guidelines, we provide comprehensive recommendations and practical tips for the pharmacologic management of patients with HF with reduced ejection fraction (HFrEF). Since the 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of HF, substantial new evidence has emerged that has informed the care of these patients. In particular, we focus on the role of novel pharmacologic therapies for HFrEF including angiotensin receptor-neprilysin inhibitors, sinus node inhibitors, sodium glucose transport 2 inhibitors, and soluble guanylate cyclase stimulators in conjunction with other long established HFrEF therapies. Updated recommendations are also provided in the context of the clinical setting for which each of these agents might be prescribed; the potential value of each therapy is reviewed, where relevant, for chronic HF, new onset HF, and for HF hospitalization. We define a new standard of pharmacologic care for HFrEF that incorporates 4 key therapeutic drug classes as standard therapy for most patients: an angiotensin receptor-neprilysin inhibitor (as first-line therapy or after angiotensin converting enzyme inhibitor/angiotensin receptor blocker titration); a β-blocker; a mineralocorticoid receptor antagonist; and a sodium glucose transport 2 inhibitor. Additionally, many patients with HFrEF will have clinical characteristics for which we recommended other key therapies to improve HF outcomes, including sinus node inhibitors, soluble guanylate cyclase stimulators, hydralazine/nitrates in combination, and/or digoxin. Finally, an approach to management that integrates prioritized pharmacologic with nonpharmacologic and invasive therapies after a diagnosis of HFrEF is highlighted.

Résumé

Dans cette mise à jour des Lignes directrices de la Société canadienne de cardiologie sur l'insuffisance cardiaque (IC), nous fournissons des recommandations complètes et des conseils pratiques pour la gestion pharmacologique des patients atteints d'IC avec une fraction d'éjection réduite (ICFER). Depuis la mise à jour complète de 2017 des Lignes directrices de la Société canadienne de cardiologie pour la prise en charge de l'IC, de nouvelles indications substantielles sont apparues au bénéfice des soins de ces patients. Nous nous concentrons en particulier sur le rôle des nouvelles thérapies pharmacologiques pour le traitement de l'ICFER, notamment les inhibiteurs des récepteurs de l'angiotensine et de la néprilysine, les inhibiteurs du nœud sinusal, les inhibiteurs du cotransporteur sodium-glucose de type 2 et les activateurs de la guanylate cyclase soluble, en conjonction avec d'autres thérapies ciblant l'ICFER et établies de longue date. Des recommandations actualisées sont également fournies dans le contexte du cadre clinique pour lequel chacune de ces molécules pourrait être prescrite ; la valeur potentielle de chaque thérapie est examinée, le cas échéant, pour une IC chronique, pour une IC apparue récemment et pour une hospitalisation pour IC. Nous définissons une nouvelle norme de soins pharmacologiques pour l'ICFER qui intègre quatre classes de médicaments thérapeutiques clés comme traitement standard pour la plupart des patients : un inhibiteur du récepteur de l'angiotensine et de la néprilysine (comme traitement de première ligne ou après titrage de l'inhibiteur de l'enzyme de conversion de l'angiotensine/inhibiteur du récepteur de l'angiotensine); un β-bloquant; un antagoniste des récepteurs des minéralocorticoïdes; et un inhibiteur du cotransporteur sodium-glucose de type 2. En outre, de nombreux patients atteints d'ICFER présenteront des caractéristiques cliniques pour lesquelles nous avons recommandé d'autres thérapies clés pour améliorer le pronostic de l'IC, notamment des inhibiteurs du nœud sinusal, des stimulateurs de guanylate cyclase soluble, l'association hydralazine/nitrates et/ou la digoxine. Enfin, une approche de traitement qui intègre des thérapies pharmacologiques prioritaires avec des thérapies non pharmacologiques et invasives après un diagnostic d'ICFER est mise en évidence.

Section snippets

Standard Therapies

On the basis of new and emerging evidence for the pharmacologic treatment of HFrEF, updated treatment recommendations are provided herein. In the current era, patients with HFrEF should treated with 4 standard therapies, in the absence of contraindications, each representing a different class of medication with unique mechanism of action. Placing a high priority on reducing cardiovascular (CV) mortality and hospitalization for HF (HHF) in most patients, these medications include: (1) an ARNI,

Sinus Node Inhibition

Resting heart rate independently predicts CV events, including HHF and death.52, 53, 54 Studies have shown that the effect of elevated heart rate on outcomes becomes apparent within 30 days of discharge from hospital.55 In systematic reviews it has been postulated that a major contributor to the benefits of β-blocker therapy in patients with HFrEF might be their rate-lowering effect.56, 57, 58

Ivabradine selectively inhibits the depolarizing If current in the sinus node. It thus requires sinus

When to refer for ICD/CRT in the current era of medical therapy for HFrEF

The decision regarding when and if an ICD should be implanted must include evaluation of the short- and long-term risks of sudden death due to a ventricular arrhythmia and death from nonarrhythmic causes. This is often a complex assessment and must integrate many factors including the presence of ischemic heart disease, burden of scar, frailty, advancing dementia, comorbidities, and adequacy of background medical therapy. In addition to ICD considerations, CRT further improves mortality and

Areas of Uncertainty and Evolving Evidence

The CCS HF Guidelines Panel identified a number of unresolved questions relevant for the management of patients with HFrEF. For the purposes of this guideline update, systematic evidence reviews were limited in scope to the therapies and settings discussed herein. However, on the basis of emerging evidence, some additional considerations are worth noting, and further research will likely inform future guidelines.

Conclusion

This CCS HF guideline update heralds a shift in the clinical approach to management of patients with HFrEF and will likely have significant practice implications. Although many areas of uncertainty remain and there is continued need for evidence to inform our approach to best practice, it is clear that knowledge translation strategies and change management will be essential to ensure that patients with HFrEF, regardless of practice setting, consistently receive the new standard for optimal

Acknowledgements

The authors acknowledge the contributions and support of Christianna Brooks (CCS staff) for her ongoing help with the guideline writing and dissemination process.

The authors also thank Dr Matthew Bennett and Dr Larry Sterns (Canadian Heart Rhythm Society) for their expertise and input into this guideline.

The authors appreciate the support of Ani Orchanian-Cheff for her assistance and expertise with evidence search and review.

The authors acknowledge the volunteer contributions of panel members,

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    The disclosure information of the authors and reviewers is available from the CCS on their guidelines library at www.ccs.ca.

    This statement was developed following a thorough consideration of medical literature and the best available evidence and clinical experience. It represents the consensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific recommendations. These recommendations are aimed to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowing optimal care to patients and families, and can be subject to change as scientific knowledge and technology advance and as practice patterns evolve. The statement is not intended to be a substitute for physicians using their individual judgement in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, diagnostic and treatment options available and available resources. Adherence to these recommendations will not necessarily produce successful outcomes in every case.

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