Differential Response to Heart Rate Reduction by Carvedilol in Heart Failure and Reduced Ejection Fraction Between
Yuji Nagatomo1,2, Tsutomu Yoshikawa2, Hiroshi Okamoto3
1Department of Cardiology, National Defense Medical College Tokorozawa Japan.
Insights
Heart rate reduction with carvedilol may not benefit heart failure patients with atrial fibrillation. Greater heart rate reduction in sinus rhythm patients improved heart function and reduced cardiovascular events.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Heart rate (HR) reduction via beta-blockers is a cornerstone in managing heart failure with reduced ejection fraction (HFrEF).
- The efficacy of HR reduction may differ in HFrEF patients with concomitant atrial fibrillation (AF) compared to sinus rhythm (SR).
- Carvedilol is a commonly used beta-blocker for HFrEF, but its impact on HR and clinical outcomes in AF patients requires further investigation.
Purpose of the Study:
- To investigate the impact of carvedilol-induced heart rate reduction on clinical outcomes in patients with HFrEF.
- To compare the effects of carvedilol on left ventricular remodeling and cardiovascular events between patients in sinus rhythm and atrial fibrillation.
- To determine if the degree of heart rate reduction influences the response to carvedilol therapy in HFrEF.
Main Methods:
- A prospective, randomized, multicenter trial (J-CHF study) involving 360 HFrEF patients treated with carvedilol.
- Patients were assigned target doses of carvedilol, with dose titration over 8 weeks.
- Patients were categorized into two groups based on median absolute change in HR at 32 weeks (∆HR >-6 beats/min vs. ≤-6 beats/min) and analyzed separately for SR and AF subgroups.
Main Results:
- In patients with SR, a greater HR reduction (Group B) was associated with more favorable changes in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic dimension (LVEDD) over 56 weeks.
- Group B (greater HR reduction) demonstrated a significantly lower rate of the primary endpoint (composite of death and cardiovascular hospitalizations) at 3 years compared to Group A.
- While ∆HR was an independent predictor of the primary endpoint in SR, this association was not observed in patients with AF.
Conclusions:
- The response to carvedilol-mediated heart rate reduction may differ significantly between HFrEF patients in sinus rhythm and those with atrial fibrillation.
- Achieving a substantial reduction in heart rate with carvedilol appears beneficial for left ventricular remodeling and long-term outcomes in SR HFrEF patients.
- Further research is warranted to optimize beta-blocker therapy strategies for HFrEF patients with atrial fibrillation.
Abstract:
Heart rate (HR) reduction by β-blocker might not benefit patients with heart failure and reduced ejection fraction (HFrEF) with atrial fibrillation (AF). The J-CHF study was a prospective randomized multicenter trial that assigned 360 HFrEF patients to a 2.5 mg/5 mg/20 mg target dose of carvedilol. Carvedilol was uptitrated over 8 weeks and then the dose was fixed. Of 321 patients available for analysis, AF was identified in 65 (20%). Using the median absolute change in HR at 32 weeks (∆HR), the subjects were further divided into group A (∆HR >-6 beats/min) and B (∆HR ≤-6 beats/min). Both in sinus rhythm (SR) and AF, baseline characteristics and achieved carvedilol dose were similar between groups A and B. In SR, the time-dependent change in left ventricular EF (LVEF) and LV end-diastolic dimension (LVEDD) over 56 weeks was more favorable in B compared with A (∆LVEF, P=0.036; ∆LVEDD, P=0.047), and ∆HR was independently associated with ∆LVEF (P=0.040). Group B had a lower rate of the primary endpoint, defined as a composite of death and hospitalization due to cardiovascular causes including acute decompensated HF at 3 years (P=0.002). ∆HR was an independent predictor of the primary endpoint (P=0.01), but this was not observed in AF. Response to the carvedilol HR reduction might differ in HFrEF between SR and AF.
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