AF and Guideline-Directed Therapy in HF: Key Points

Newman JD, O’Meara E, Böhm M, et al.
Implications of Atrial Fibrillation for Guideline-Directed Therapy in Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol 2024;83:932-950.

The following are key points to remember from a state-of-the-art review on implications of atrial fibrillation (AF) for guideline-directed therapy in patients with heart failure (HF):

  1. AF and HF share common risk factors and coexist in up to 50% of patients. HF is a risk factor for incident AF and portends a higher stroke risk with AF. Similarly, AF in HF is associated with more symptoms, hospitalizations, and mortality risk across the entire spectrum of ejection fraction (EF).
  2. A secondary analysis of HF trials suggests that angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) prevent new-onset AF. Compared with ACE inhibitors and ARBs, angiotensin receptor neprilysin inhibitors (ARNIs) did not lower AF risk in HF patients (regardless of EF) in trials. However, smaller studies suggest that ARNIs also promote reverse atrial remodeling in HF patients with AF.
  3. In beta-blocker (BB) trials among patients with HF and reduced EF (HFrEF), patients on BBs had a lower incidence of AF and atrial flutter (AF/flutter). Efficacy of BBs in HFrEF patients with AF is conflicting between trials (lesser benefits in HFrEF with AF than HFrEF in sinus rhythm) and observational studies due to study design limitations. Furthermore, BB benefits in patients with HF and preserved EF (HFpEF) and HF with mid-range EF remain unknown.
  4. A post hoc analysis of trials suggests that eplerenone reduced incident AF in HFrEF and reduced mortality and hospitalization in HFrEF patients with and without AF. However, in HFpEF patients, spironolactone did not reduce AF incidence or recurrence but benefits with spironolactone persisted regardless of AF status. A trial with finerenone in type 2 diabetes patients with chronic kidney disease reduced both incident AF and HF.
  5. A post hoc analysis of sodium-glucose cotransporter-2 (SGLT2) inhibitor trials in diabetes mellitus patients with or at high risk for atherosclerotic cardiovascular disease suggests a reduced risk for AF/flutter with SGLT2 inhibitors. However, SGLT2 inhibitor trials in HFrEF and HFpEF do not show reduced AF/flutter risk with the group but benefits of SGLT2 inhibitors in HF are consistent regardless of AF status.
  6. Contemporary data examining effectiveness of digoxin in HF patients with AF are limited to observational data. These data suggest that when used in HF, a digoxin level of 0.5-0.9 ng/mL should be targeted. Newer trials are examining efficacy of digoxin in HF.
  7. Clinical trials and meta-analyses suggest increased risk of AF with ivabradine use in HFrEF patients but not HFpEF patients. However, data on ivabradine in HFpEF are limited to small studies and likely underpowered to assess impact on AF. Ivabradine use is associated with heart rate lowering in AF.
  8. The benefit of hydralazine and nitrates in African American HFrEF patients is consistent regardless of AF status. Benefit of vericiguat in HF patients with EF ≤45% was also consistent regardless of AF status but did not change AF incidence.
  9. The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide in HFpEF patients was associated with fewer adverse events due to AF. Studies show that GLP-1 agonists are associated with an increased heart rate but whether these agents incite AF remains unknown.
  10. For HF patients (regardless of EF), rhythm control for AF with catheter ablation has been associated with reduced morbidity and mortality. In addition, rhythm control with antiarrhythmic drugs is also of benefit. However, among HFpEF patients undergoing AF ablation, data suggest an increased need for repeat ablation.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Atrial Fibrillation, Heart Failure

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