NATIONAL HARBOR, MD. – In beta-blocker treatment of heart failure, dose matters; heart rate, not so much.
When using beta-blockers to treat patients with heart failure and reduced ejection fraction, administering a high, evidence-backed dosage of the drug had much more beneficial impact than did getting patients to a low heart rate, according to a post hoc analysis of data from more than 2,000 patients.
The finding provides new evidence supporting “titrating the beta-blocker to evidence-based, high dosages of a beta-blocker and not holding back,” Mona Fiuzat, Ph.D., said in an interview at the annual scientific meeting of the Heart Failure Society of America. “It’s not just lowering the heart rate; there is something else, other mechanisms [of beta-blocker effects] that may be of greater benefit” to patients beyond heart-rate reduction when patients they receive the full dosage of beta-blocker treatment that had been shown effective in the randomized trials run about 2 decades ago.
“The point of our report is that if you have [heart failure with reduced ejection fraction] patients on a beta-blocker, they will be better off by increasing the dose” to the target level rather than by adding an additional, non–beta-blocker drug, such as ivabradine (Corlanor), to further reduce heart rate, said Dr. Fiuzat, a clinical pharmacologist and heart-failure researcher at Duke University in Durham, N.C. In the trial that enrolled the 2,320 patients included in the current analysis, half the patients were not on their target beta-blocker dosage.
Some clinicians are too heart-rate focused, she said. “Our results show that there is added benefit from using the full beta-blocker dosage even when the patient’s heart rate is already low.”
The analysis run by Dr. Fiuzat and her associates used data collected in HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), a randomized, controlled study that assessed the impact of exercise training on patients with heart failure with reduced ejection fraction (JAMA 2009 Apr 8;301[14]:1439-50). All patients received usual care (and the intervention group also received exercise training), which meant they were on whichever beta-blocker and dosage their individual physician prescribed.
The current analysis converted these baseline dosages into carvedilol (Coreg) equivalents and identified the dosage levels as either low, defined as a daily carvedilol equivalent of less than 25 mg/day, or high, a daily equivalent of at least 25 mg/day. The analysis also categorized heart rate at baseline into a high rate defined as at least 70 beats/min, and a low rate of less than 70 beats/min. At entry, 71% of patients were on a high beta-blocker dosage (although in many cases not their full, ideal dosage), and 52% of patients had a high heart rate.
The new analysis showed that after a median follow-up of 2.5 years, the rate of all-cause death and all-cause hospitalization was significantly higher among patients who entered the study on a low beta-blocker dosage and with a high heart rate compared with patients in the other three groups: low dosage/low heart rate, high dosage/high heart rate, and high dosage/low heart rate. In addition, the results showed that a high beta-blocker dosage at baseline mitigated the impact of a high heart rate; patients in this subgroup had outcomes comparable to those of patients on a high beta-blocker dosage with a low heart rate.
In an analysis that adjusted for baseline differences in several clinical and demographic variables, patients on a high beta-blocker dosage had a statistically significant 13% reduced rate of all-cause death or all-cause hospitalization compared with patients on a low-dosage beta-blocker. In contrast, baseline heart rate had no statistically significant impact on outcomes, Dr. Fiuzat and her associates reported in an article published online concurrently with the presentation of the results at the meeting by one of Dr. Fiuzat’s colleagues (JACC: Heart Failure 2015. doi: 10.1016/j.jchf.2015.09.002]).
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