Author + information
- Received June 10, 2015
- Revision received August 19, 2015
- Accepted September 14, 2015
- Published online February 1, 2016.
- Mona Fiuzat, PharmDa,∗ (, )
- Daniel Wojdyla, MSa,
- Ileana Pina, MDb,
- Kirkwood Adams, MDc,
- David Whellan, MDd and
- Christopher M. O’Connor, MDa,e
- aDuke University and Duke Clinical Research Institute, Durham, North Carolina
- bMontefiore Einstein Center for Heart and Vascular Care, Bronx, New York
- cUniversity of North Carolina, Chapel Hill, North Carolina
- dThomas Jefferson University, Philadelphia, Pennsylvania
- eInova Heart & Vascular Institute, Falls Church, Virginia
- ↵∗Reprint requests and correspondence:
Dr. Mona Fiuzat, Cardiology, Duke University Medical Center, Box 3356, Durham, North Carolina 27710.
Objectives This study aimed to compare whether reduced heart rate (HR) or higher beta-blocker (BB) dose affected outcomes to a greater extent in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial population.
Background Recent data have shown that HR is an important modifiable factor in reducing mortality in heart failure (HF) patients. It has also been shown that titration of doses of BBs improves outcomes of morbidity and mortality in chronic HF patients with reduced ejection fraction. We aimed to compare whether reduced HR or higher BB dose affected outcomes to a greater extent in the HF-ACTION trial population.
Methods HF-ACTION was a randomized, multicenter trial enrolling 2,331 ambulatory HF patients with systolic dysfunction (New York Heart Association functional class II to IV, left ventricular ejection fraction <0.35) randomized to exercise training versus usual care, with median follow-up of 2.5 years. BB dose at baseline was standardized by use of carvedilol equivalents. BB dose and HR were analyzed by discrete groups (higher/lower dose; higher/lower HR). The relationship of BB dose, HR, and the primary endpoint of all-cause mortality or all-cause hospitalization and other cardiovascular secondary endpoints were determined before and after adjustment for variables found to be significantly associated with outcome in the HF-ACTION cohort.
Results There was a significant inverse relationship between either BB dose (higher was better) or HR (lower was better) and all-cause death or hospitalization in unadjusted analysis; however, only BB dose was significant for improved mortality outcomes. After adjustment for other predictors of outcome, only BB dose remained significant for improving all-cause death or hospitalization. BB dose, but not HR, was associated with improved outcomes of other cardiovascular endpoints in unadjusted analysis but did not remain significant when adjusted for other predictors of outcome in this cohort.
Conclusions There were more associated improvements in outcomes with higher BB dose than with reduced HR in this well-treated HF cohort with systolic dysfunction, which suggests that titration of BB doses may confer a greater benefit than reduction of HR in such patients. (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]; NCT00047437)
The HF-ACTION trial was funded by the National Institutes of Health and the National Heart, Lung, and Blood Institute, Bethesda, Maryland. All authors have reported that they have no relationships relevant to the contents of this paper to report. John R. Teerlink, MD, served as the Guest Editor for this article.
- Received June 10, 2015.
- Revision received August 19, 2015.
- Accepted September 14, 2015.
- 2016 American College of Cardiology Foundation