By providing best evidence-based guidance on how to diagnose and treat disease, clinical practice guidelines (CPGs) have become an essential part of medical practice. They not only affect direct patient care but also are translated into operational processes for health care facilities, coverage decisions, and metrics to judge care quality. Accordingly, CPGs must be all-inclusive yet practical, scientifically erudite yet applicable to daily practice, evidence-based yet providing guidance where evidence is lacking, and timely but not premature. In this regard, the CPGs from the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) and the European Society of Cardiology (ESC) are particularly important on the basis of their global reach. In our interconnected global community, CPGs must ideally be congruent across various regions, unless there are reasons for variation. Discordant recommendations for the same disease state on the basis of the same data can cause confusion and/or inaction.
Since the last published CPG for heart failure (HF), the field has progressed rapidly with much new evidence. As such, the authors of the new ACCF/AHA/HFSA and ESC guidelines had a monumental task of addressing everything from how we define HF itself to the multiple novel pharmacological and nonpharmacological interventions now available.[1,2] With few exceptions, HF has a similar clinical presentation worldwide. In fact, the new universal definition of HF and approaches to confirm the diagnosis have been agreed on by multiple professional societies globally. Despite this, the approach to treatment appears not to be entirely universal.
There are differences in the approach to standard therapy for patients in these 2 otherwise impressive documents (Table). Both guidelines firmly establish that quadruple therapy with angiotensin receptor neprilysin inhibitors (ARNIs), evidence-based β-blockers, mineralocorticoid receptor antagonists, and sodium glucose cotransporter-2 inhibitors now form the new foundational standard for guideline-directed medical therapy for HF with reduced ejection fraction (HFrEF). The ACCF/AHA/HFSA guidelines, however, firmly declare that the ARNI should be the preferred renin-angiotensin modulator with a class 1A recommendation, and that the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be used "when the use of ARNI is not feasible." The ESC guidelines give ARNI a 1B recommendation, stating that ARNI is recommended "as a replacement for angiotensin-converting enzyme inhibitors" in suitable patients who remain symptomatic, although an ARNI can be considered as first-line. The ACCF/AHA/HFSA give a 1A recommendation for hydralazine-isosorbide dinitrate for self-identified Black patients, whereas the ESC gives a class 2A recommendation citing the lack of "clear evidence to suggest the use of this fixed-dose combination therapy in all patients with HFrEF."[1,2] The authors of the ESC guidelines acknowledge the Food and Drug Administration endorsement of ARNIs and mineralocorticoid receptor antagonists for the treatment of heart failure with preserved ejection fraction (HFpEF). However, they do not provide a class or level of recommendation for either of these pharmacotherapies, largely because the benefit of these drugs was only evident in prespecified subgroups (ie, women and participants with ejection fraction [EF] <57% for ARNI) and post hoc analyses (ie, participants with EF <55%, and participants recruited in the Americas for mineralocorticoid receptor antagonists). In contrast, the ACC/AHA/HFSA endorse the use of ARNIs, mineralocorticoid receptor antagonists and sodium glucose cotransporter-2 inhibitors for the treatment of HF with preserved EF.
Another major difference in these guidelines is the role for primary prevention implantable-cardioverter defibrillators (ICD). The ESC guidelines give a 1A recommendation for ICD in patients with an ischemic HF pathogenesis, but the recommendation has been downgraded to a 2A for patients with a nonischemic HF pathogenesis. The ACC/AHA/HFSA continue to endorse a 1A recommendation for primary prevention ICD regardless of HF pathogenesis. The authors of both documents acknowledge that improvements in guideline-directed medical therapy have reduced but not eliminated rates of sudden cardiac death in patients with HF, perhaps to a greater degree in patients with nonischemic disease. Still, different interpretations of the same data by expert guideline committees can be confusing for practicing clinicians and distressing for patients, particularly as it pertains to a therapy as significant as an implanted device.
What factors could account for the different recommendations between the 2 guidelines? They are certainly not based on the pathobiology of the HF syndrome itself, and more likely to be based on the populations of patients under consideration and the economic conditions of the health care systems that provide care for those patients. Currently, HF affects more than 26 million people worldwide, with a global economic burden of ~$108 billion annually, largely because of the cost of hospitalizations. The United States is the biggest contributor at 28.4% of total global expenditures on HF care, whereas Europe accounts for 6.8%. Appropriately, the ACCF/AHA/HFSA guidelines now include value statements for select recommendations where high-quality cost-effectiveness studies have been published for the intervention under consideration. This is a major step in the right direction for which the authors should be commended. Although neither ARNIs nor sodium glucose cotransporter-2 inhibitors are generic and can be of considerable cost to patients, both therapies provide high economic value, in part because of the significant reduction in hospitalizations for treated patients across the spectrum of EF. Similarly, the higher rate of hospitalization for Black Americans likely justifies the higher level of recommendation for hydralazine-isosorbide dinitrate in this subgroup given its effects on morbidity and mortality. Although more trials are needed to reevaluate the mortality benefit of primary prevention ICD in the setting of contemporary HF guideline-directed medical therapy, the likelihood of life-threatening ventricular arrhythmias is high in patients with ischemic and nonischemic disease. Thus, this therapy is deemed to be of high economic value by the ACCF/AHA/HFSA.
What additional data are needed to harmonize CPG across continents, and provide a universal set of recommendations to guide treatment of a universal definition of HF? The benefit of ARNIs and sodium glucose cotransporter-2 inhibitors with EF below normal is evident, which the ACCF/AHA/HFSA guidelines support, but additional study is needed among individuals with left ventricular EF within the normal range. Further, a reevaluation of the role of primary prevention ICD in this era of quadruple therapy for HF with reduced EF is clearly warranted. As the pace of scientific progress continues to accelerate, the existence of mechanisms that enable these guidelines to be living documents with regular updates as new practice-altering data become available is required.
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Circulation. 2022;145(18):1371-1373. © 2022 American Heart Association, Inc.