European and American guidelines for the management of patients with heart failure - different recommendations based on the same research results?

Abstract

Currently, the main reasons for significant changes in medical guidelines are new results of randomized clinical trials. In addition to the direct impact on the treatment of individual patients, the solutions proposed in the guidelines correlate with the decisions of health care payers in individual countries, and this largely translates into the overall quality of medical care. Considering the importance of guidelines of scientific societies, they must be comprehensive, objective, and at the same time, due to the constant technological and pharmacological progress, it is necessary to develop mechanisms thanks to which these guidelines can be regularly updated as new clinical data become available. The guidelines of the European Society of Cardiology (ESC) (1) and the joined guidelines of the American College of Cardiology Foundation (ACCF)/ American Heart Association (AHA)/ Heart Failure Society of America (HFSA) (2) for the management of patients with heart failure are particularly important due to their global reach. The authors of both documents restated both the definition of HF itself and novel pharmacological and non-pharmacological interventions. While the definition of the disease entity and general assumptions seem universal, the detailed treatment regimens differ (Table 1). The current classification of HF is as follows: HFrEF (HF with reduced ejection fraction (EF)): LVEF ≤40%; HFmrEF (HF with mildly reduced EF): LVEF 41-49%; HFpEF (HF with preserved EF): LVEF ≥50%. According to American guidelines we can distinguish also HFimpEF (HF with improved EF): previous LVEF ≤40% and followup measurement of LVEF >40%; and four stages of progression HF from A to D (At risk for HF -> Pre-HF -> symptomatic HF -> Advanced HF), with independent recommendations for each of them. Both publications indicate in the group of patients with HFrEF a 4-drug treatment regimen based on: 1) drugs affecting the renin-angiotensin-aldosterone system (RAAS): angiotensin converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), angiotensin receptor neprilysin inhibitor (ARNI), 2) B-blockers (BB), 3) mineralocorticoid receptor antagonists (MRA), 4) sodium glucose cotransporter-2 inhibitors (SGLT2i), which is becoming a major player in the treatment of heart failure. The ACCF/AHA/HFSA guidelines strongly identify ARNI as the preferred RAAS modulator with a class Ia recommendation and state that the use of ACEI or ARB may be used "when the use of ARNI is not possible." The ESC guidelines appear to be more conservative, establishing the strength of the recommendations for the use of ARNI as Ib, stating that ARNI is recommended "as a replacement for angiotensin converting enzyme inhibitors" in suitable patients who remain symptomatic despite optimal treatment, although ARNI can be considered a first-line drug (class IIb). There is no differences in recommendation of loop diuretics (class I), ivabradine (class IIa), verciguat (class IIb) or digoxin (class IIb). The most significant difference in the proposed treatment regimens of this group of patients concerns the use of hydralazine-isosorbide dinitrate. The ACCF/AHA/HFSA indicates recommendation class Ia for African-Americans, while the ESC provides a class IIa recommendation, citing the lack of "clear evidence to suggest the use of this fixed-dose combination therapy in all patients with HFrEF." In the remaining groups of patients with heart failure (preserved and mildly reduced EF value), the differences in recommendations are even more pronounced. The European guidelines did not issue recommendations for the use of SGLT2i in patients with HFmrEF or for any of the drug in patients with HFpEF in contrast to the ACCF/AHA/HFSA guidelines, which support the use of ARNI, mineralocorticoid receptor antagonists, and SGLT2i in the treatment of HF with preserved EF with recommendation class IIb, IIb and IIa respectively.