1. 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.

The Canadian Cardiovascular Society (CCS) Heart Failure Guidelines Program provides guidance to clinicians, policymakers, and health systems as to the evidence supporting existing and emerging management of patients with heart failure (HF). Since the 2017 comprehensive update of the CCS guidelines for the management of HF,^[1] substantial new evidence has emerged, particularly relevant to the management of patients with HF with reduced ejection fraction (HFrEF). The present CCS HF guideline update defines a contemporary standard of care for the HFrEF patient population on the basis of the totality of available evidence. This update focuses on the role of newer pharmacologic therapies for HFrEF including angiotensin receptor-neprilysin inhibitor (ARNI), sinus node inhibitor, sodium glucose transport 2 (SGLT2) inhibitor, and soluble guanylate cyclase (sGC) stimulator, in conjunction with well established and conventional HFrEF therapies. Where evidence exists, updated recommendations are provided with respect to the clinical setting in which each of these agents may be prescribed; the potential value of each therapy is reviewed, where relevant, in the setting of chronic HF, new onset HF, and for HF hospitalization. A consensus approach to management that integrates prioritized pharmacologic with nonpharmacologic and invasive therapies after a diagnosis of HFrEF is highlighted.

The scope of this guideline update is limited to key pharmacologic therapies for patients with HFrEF. A detailed description of nonpharmacologic management, including advance care planning, multidisciplinary care, remote monitoring, and diet and exercise prescription are not addressed. Management of important comorbidities including coronary disease, atrial fibrillation, functional mitral regurgitation, chronic kidney disease, diabetes, and iron deficiency have also been addressed in previous guideline updates,^[1],[2] although the Panel acknowledges that evidence is quickly evolving in many of these areas.

The composition and roles of the primary and secondary panels, systematic review strategy, and methods for formulating the recommendations are described at www.ccs.ca. The recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) standards.^[3] Primary panelists were responsible for writing and reviewing the document, and the secondary panelists provided critical input from provider and patient perspectives.