Background: Rate-control is a front-line therapy in patients with persistent or permanent atrial fibrillation (AF). However, the independent association of heart rate with patient outcomes and the optimal level of heart rate control are still unknown, including for patients who have AF and heart failure (HF).
Purpose: To assess the relationship between heart rate (ventricular response in AF) and clinical outcomes in patients with persistent or permanent AF, with and without HF.
Methods: We included in this post-hoc analysis all patients enrolled in the ARISTOTLE trial with persistent or permanent AF (n=15,365). Heart rate was measured by electrocardiogram at baseline. Socio-demographic and clinical characteristics, including medications and selected biomarkers (NT-proBNP, troponin I and T, GDF-15), were compared according to the level of heart rate (categorized as <80 bpm, 80–119 bpm, and ≥120 bpm). Relationships between heart rate (as a continuous variable) and clinical endpoints were assessed using Cox regression models. Adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were calculated. The analysis was performed in the overall population and in those with HF.
Results: Patients with faster heart rate (≥120 bpm [n=1094]) were younger and more likely to have a history of HF or reduced ejection fraction than patients with heart rates of either 80–119 bpm (n=6409) or <80 bpm (n=7862). They were also more likely to be on beta-blockers (69%), digoxin (42%), amiodarone (14%), or verapamil (6%). All biomarkers were lower in the group of patients with controlled heart rate (80–119 bpm) as compared with patients with heart rate <80 bpm and those with heart rate ≥120 bpm. In the overall population, increase in heart rate (per 10 beats per minute) was associated with a higher risk of death (HR 1.04, 95% CI [1.01–1.07]) and HF hospitalizations (HR 1.06, 95% CI [1.01–1.10]) in the adjusted analysis (p≤0.01). In patients with HF, increase in heart rate was associated with a high risk of HF hospitalizations (HR 1.06, 95% CI [1.01–1.11]) in the adjusted analysis (p=0.02), but not death.
Conclusion: In patients with persistent or permanent AF, a faster heart rate is associated with a modest but significant increase in death and HF hospitalizations in the overall population, and with an increase in HF hospitalizations in patients with HF. More randomized trials are needed to determine whether, how, and among whom heart rate should be more aggressively managed in patients with AF.