Effect of Beta-Blocker Dose on Survival after Acute Myocardial Infarction

Jeffrey Goldberger, Robert O. Bonow, Michael Cuffe, Lei Liu, Yves Rosenberg, Prediman K. Shah, Sidney C. Smith, Haris Subačius

Research output: Contribution to journalArticle

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Abstract

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)

Original languageEnglish (US)
Pages (from-to)1431-1441
Number of pages11
JournalJournal of the American College of Cardiology
Volume66
Issue number13
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Myocardial Infarction
Survival
Propensity Score
Confidence Intervals
Registries
Randomized Controlled Trials
Therapeutics
Outcome Assessment (Health Care)
Mortality
Research

Keywords

  • adrenergic beta-antagonists
  • follow-up studies
  • registries
  • survival analysis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effect of Beta-Blocker Dose on Survival after Acute Myocardial Infarction. / Goldberger, Jeffrey; Bonow, Robert O.; Cuffe, Michael; Liu, Lei; Rosenberg, Yves; Shah, Prediman K.; Smith, Sidney C.; Subačius, Haris.

In: Journal of the American College of Cardiology, Vol. 66, No. 13, 01.01.2015, p. 1431-1441.

Research output: Contribution to journalArticle

Goldberger, J, Bonow, RO, Cuffe, M, Liu, L, Rosenberg, Y, Shah, PK, Smith, SC & Subačius, H 2015, 'Effect of Beta-Blocker Dose on Survival after Acute Myocardial Infarction', Journal of the American College of Cardiology, vol. 66, no. 13, pp. 1431-1441. https://doi.org/10.1016/j.jacc.2015.07.047
Goldberger, Jeffrey ; Bonow, Robert O. ; Cuffe, Michael ; Liu, Lei ; Rosenberg, Yves ; Shah, Prediman K. ; Smith, Sidney C. ; Subačius, Haris. / Effect of Beta-Blocker Dose on Survival after Acute Myocardial Infarction. In: Journal of the American College of Cardiology. 2015 ; Vol. 66, No. 13. pp. 1431-1441.
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abstract = "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)",
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AU - Liu, Lei

AU - Rosenberg, Yves

AU - Shah, Prediman K.

AU - Smith, Sidney C.

AU - Subačius, Haris

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N2 - 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)

AB - 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)

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