Author + information
- Received May 23, 2015
- Revision received July 20, 2015
- Accepted July 21, 2015
- Published online September 29, 2015.
- Jeffrey J. Goldberger, MD, MBA∗∗ (, )
- Robert O. Bonow, MD∗,
- Michael Cuffe, MD†,
- Lei Liu, PhD‡,
- Yves Rosenberg, MD, MPH§,
- Prediman K. Shah, MD‖,
- Sidney C. Smith Jr., MD¶,
- Haris Subačius, MA∗,
- OBTAIN Investigators
- ∗Center for Cardiovascular Innovation and the Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- †Hospital Corporation of America, Brentwood, Tennessee
- ‡Department of Preventive Medicine, Northwestern University, Chicago, Illinois
- §Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
- ‖Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California
- ¶Heart and Vascular Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- ↵∗Reprint requests and correspondence:
Dr. Jeffrey J. Goldberger, Northwestern University Feinberg School of Medicine, Division of Cardiology, 676 North Saint Clair, Arkes 600, Chicago, Illinois 60611.
Background Beta-blocker therapy after acute myocardial infarction (MI) improves survival. Beta-blocker doses used in clinical practice are often substantially lower than those used in the randomized trials establishing their efficacy.
Objectives This study evaluated the association of beta-blocker dose with survival after acute MI, hypothesizing that higher dose beta-blocker therapy will be associated with increased survival.
Methods A multicenter registry enrolled 7,057 consecutive patients with acute MI. Discharge beta-blocker dose was indexed to the target beta-blocker doses used in randomized clinical trials, grouped as >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target dose. Follow-up vital status was assessed, with the primary endpoint of time-to-death right-censored at 2 years. Multivariable and propensity score analyses were used to account for group differences.
Results Of 6,682 patients with follow-up (median 2.1 years), 91.5% were discharged on a beta-blocker (mean dose 38.1% of the target dose). Lower mortality was observed with all beta-blocker doses (p < 0.0002) versus no beta-blocker therapy. After multivariable adjustment, hazard ratios for 2-year mortality compared with the >50% dose were 0.862 (95% confidence interval [CI]: 0.677 to 1.098), 0.799 (95% CI: 0.635 to 1.005), and 0.963 (95% CI: 0.765 to 1.213) for the >0% to 12.5%, >12.5% to 25%, and >25% to 50% of target dose groups, respectively. Multivariable analysis with an extended set of covariates and propensity score analysis also demonstrated that higher doses were not associated with better outcome.
Conclusions These data do not demonstrate increased survival in patients treated with beta-blocker doses approximating those used in previous randomized clinical trials compared with lower doses. These findings provide the rationale to re-engage in research to establish appropriate beta-blocker dosing after MI to derive optimal benefit from this therapy. (The PACE-MI Registry Study—Outcomes of Beta-blocker Therapy After Myocardial Infarction [OBTAIN]: NCT00430612)
This research was supported by grant 5U01HL080416 from the National Heart, Lung, and Blood Institute of the National Institutes of Health. The views expressed in this manuscript are the authors' and do not necessarily reflect those of the National Institutes of Health or the Department of Health and Human Services. Dr. Liu is a consultant to Celladon, Outcome Research Solutions, and Zensun. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received May 23, 2015.
- Revision received July 20, 2015.
- Accepted July 21, 2015.
- American College of Cardiology Foundation