Heart rate control by carvedilol in Japanese patients with chronic atrial fibrillation: The AF Carvedilol study.

BACKGROUND

β-Blockers are used to control heart rate (HR) in patients with atrial fibrillation (AF). However, the appropriate dosage and efficacy of carvedilol in Japanese AF patients are yet to be clarified.

METHODS

In this multicenter, randomized, double-blind study, Japanese patients with persistent or permanent AF received carvedilol for 6 weeks in the following three dosage-regimen groups: 5-mg fixed-dose (n=42), 10-mg dose-escalation (n=42), or 20-mg dose-escalation (n=43). To evaluate the efficacy of each dosage regimen and the dose-response relationship, changes in 24-h mean HR (mHR) on Holter electrocardiograms from baseline to weeks 2, 4, and 6 were determined as primary endpoints. The effects on circadian changes in HR, the proportion of patients achieving target HR, clinical symptoms, and adverse events were also examined.

RESULTS

After 2 weeks, carvedilol 5mg decreased 24-h mHR significantly [6.6 (95% CI: 5.2-8.0)beats/min, p<0.0001]. After 6 weeks, carvedilol showed a trend of dose-dependent HR reduction (p=0.0638): 7.6 (5.4-9.8) in the 5-mg fixed-dose group; 8.9 (6.7-11.1) in the 10-mg dose-escalation group; and 10.6 (8.4-12.8)beats/min in the 20-mg dose-escalation group. There were no serious adverse events related to carvedilol.

CONCLUSIONS

In Japanese patients with persistent or permanent AF, carvedilol at 5mg once daily demonstrated a significant HR reduction, and step-wise dose escalation from 5mg to 20mg showed a trend of dose-dependent HR reduction.