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- This nationwide study examined the effect of treatment with rate-control drugs on all-cause mortality in atrial fibrillation (AF) patients. Treated patients received either beta blockers (BBs; n = 43,879), calcium channel blockers (CCB; n = 18,466), or digoxin (n = 38,898).
- The risk of mortality was significantly lower in patients receiving BBs or CCBs in comparison with untreated control patients (n = 168,678), with the greatest risk reduction observed in patients receiving BBs. Conversely, digoxin was associated with a higher risk of mortality.
Abstract
This abstract is available on the publisher’s site.
BACKGROUND
Current American and European guidelines emphasized the importance of rate control treatments in treating atrial fibrillation (AF) with a Class I recommendation, although data about the survival benefits of rate control are lacking. The goal of the present study was to investigate whether patients receiving rate control drugs had a better prognosis compared to those without rate-control treatment.
METHODS AND RESULTS
This study used the “National Health Insurance Research Database” in Taiwan. There were 43,879, 18,466 and 38,898 AF patients enrolled in the groups of beta-blockers (BBs), calcium channel blockers (CCBs) and digoxin, respectively. The reference group consisted of 168,678 subjects who did not receive any rate-control drug. The clinical endpoint was all-cause mortality. During a follow-up of 4.9±3.7 years, mortality occurred in 88,263 patients (32.7%). After the adjustment for the baseline differences, the risk of mortality was lower in patients receiving BBs (adjusted hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.74-0.78) and CCBs (adjusted HR = 0.93, 95% CI = 0.90-0.96) compared to those who did not receive rate-control medications. On the contrary, the digoxin group had a higher risk of mortality with an adjusted HR of 1.12 (95% CI = 1.10-1.14). The results were consistently observed in subgroup analyses and among the cohorts after propensity matching.
CONCLUSIONS
In this nationwide AF cohort, the risk of mortality was lower for patients receiving rate-control treatments with BBs or CCBs, and the use of BBs was associated with a largest risk reduction. Digoxin use was associated with greater mortality. Prospective randomized trials are necessary to confirm these findings
ARYAN'S BLOG 
These 2 studies examine the effect of heart rate (HR) on clinical outcomes in patients with Atrial Fibrillation (AF).
The first study included 2812 outpatients with permanent AF in the non-randomized Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). The population was stratified by baseline resting HR (<60 bpm; 60 to 79 bpm; 80 to 109 bpm; and ≥110 bpm) and followed for a median of 24 months (interquartile range of 18 to 30 months). The authors performed a multivariable analysis using heart rate as a continuous, time-dependent covariate and demonstrated that the relationship between heart rate and mortality/adverse events was nonlinear, with an inflection point at 65 bpm. Specifically, decreasing HR below 65 bpm and increasing HR above 65 bpm were associated with increasing all-cause mortality (adjusted HR = 1.15 per 5-bpm decrease ≤65 bpm; 95% confidence interval [CI], 1.01-1.32; P = .04; adjusted HR = 1.10 per 5-bpm increase >65 bpm; 95%CI, 1.05 to 1.15; P < .0001), as well as adverse events (SSE, major bleeding, new heart failure, MI, revascularization, all-cause hospitalization, and all-cause death; adjusted HR = 1.10 per 5-bpm decrease ≤65 bpm; 95%CI, 1.02 to 1.19; adjusted HR = 1.03 per 5-bpm increase >65 bpm; 95%CI, 1.00 to 1.06).
A complimentary study by Chao et al suggested that the method utilized to reduce the heart rate had differential benefits. This study utilized the “National Health Insurance Research Database” in Taiwan to identify 43,879 AF patients on beta-blockers (BB), 18,466 on rate-limiting calcium channel blockers (CCBs), and 38,898 AF patients on digoxin. Over the follow-up period of 4.9 ± 3.7 years, mortality occurred in 88,263 patients (32.7%). After the adjustment for the baseline co-variates, the mortality risk was lower in patients receiving BBs (adjusted HR = 0.76, 95%CI = 0.74-0.78, P < .001) and CCBs (adjusted HR = 0.93, 95%CI = 0.90-0.96, P < .001) compared with those who did not receive rate-control medications. In contrast, the digoxin group had a higher risk of mortality with an adjusted HR of 1.12 (95%CI = 1.10-1.14, P < .001) compared with that of the reference group. These findings were consistent in a propensity-matched analysis.
Taken together, these “real-world” studies suggest that stricter rate control targets are associated with improved patient outcomes, and the use of BB and CCBs are the preferred means to achieve this target.