Reducing heart rate benefits HF patients in sinus rhythm, but not those with AF
Paris, France | Targeting heart rate to improve mortality in heart failure with reduced ejection fraction: a comparison of sinus rhythm and atrial fibrillation
Presented at ESC Heart Failure 2017 by John CLELAND (London, United Kingdom), on behalf of the Beta-blockers in Heart Failure Collaborative Group
Individual patient data of eleven randomised controlled trials (MDC 1993, CIBIS 1994, US-HF 1996, ANZ 1997, CIBIS-II 1999, MERIT-HF 1999, COPERNICUS 2001, CAPRICORN 2001, BEST 2001, CHRISTMAS 2003 and SENIORS 2005) were pooled, amounting to data of 18637 HF patients. All RCTs had mortality as a major trial endpoint, were unconfounded head-to-head trials, and had planned follow-up of over 6 months, and included at least 300 patients.
The aim was to compare the effect of betablocker use in patients in sinus rhythm with those with atrial fibrillation (AF). At baseline, it was noted that those in the higher heart rate category (>90 bpm) were slightly sicker, with a larger proportion having HF NYHA class III/IV, and a lower LVEF, while age was somewhat lower than in the other two heart rate categories (<70 and 70-90 bpm).
- In patients in sinus rhythm, those with a lower heart rate at baseline showed lower all-cause mortality than those with a higher heart rate, a pattern that was not seen in patients with AF.
- When modelling the HR for all-cause mortality based on baseline heart rate, a positive statistically significant correlation was seen in those in sinus rhythm (HR: 1.11 per 10 bpm, 95%CI: 1.07-1.15, P<0.0001). In AF, the slope was flatter and did not reach statistical significance (HR: 1.03 per 10 mm, 95%CI: 0.97-1.08, P=0.38).
- In sinus rhythm patients, the efficacy of betablocker treatment was independent of heart rate at baseline, with relative risk reductions of 18-29% in the three heart rate categories.
- In AF, no effect of betablocker treatment was seen (HR: 0.97, 95%CI: 0.83-1.14, P=0.73).
- A dose-dependent reduction in all-cause mortality was seen in patients in sinus rhythm treated with beta-blockers. It should be noted that also the highest dose of placebo showed reduced mortality as compared to the other placebo groups.
- All-cause mortality was lower in those with lower follow-up heart rates in those in sinus rhythm.
- In AF, no clear pattern was seen of baseline heart rate and all-cause mortality.
Thus, these pooled data show that higher baseline heart rate is associated with higher mortality in sinus rhythm, but makes no difference in AF. A higher dose of betablocker (and of placebo!) is associated with lower mortality in sinus rhythm, and a lower attained heart rate is associated with lower mortality in sinus rhythm, but does not affect mortality in AF.
Heart rate turned out not to be a good predictor of response to treatment with a betablocker, as efficacy was similar in all heart rate categories. Thus, Dr. Cleland concluded that in clinical practice, it is important to not only attain the proper dose of betablocker, but also to lower heart rate, possibly with an additional agent. In AF, there is little evidence to expect a benefit.
Our coverage of ESC HF 2017 is based on the information provided during the congress.