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Original Investigation |

Association of β-Blocker Therapy With Risks of Adverse Cardiovascular Events and Deaths in Patients With Ischemic Heart Disease Undergoing Noncardiac Surgery:  A Danish Nationwide Cohort Study

Charlotte Andersson, MD, PhD1,2; Charlotte Mérie, MD2; Mads Jørgensen, MB2; Gunnar H. Gislason, MD, PhD2,3; Christian Torp-Pedersen, MD, DSc4; Charlotte Overgaard, PhD4; Lars Køber, MD, DSc5; Per Føge Jensen, MD, PhD, MHM6; Mark A. Hlatky, MD1
[+] Author Affiliations
1Department of Health Research and Policy, Stanford University, School of Medicine, Stanford, California
2Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark
3National Institute of Public Health, University of Southern Denmark, Copenhagen
4Institute of Health, Science and Technology, Aalborg University, Aalborg, Denmark
5The Heart Center, Rigshospitalet, Copenhagen, Denmark
6Department of Cardiothoracic Anesthesia, The Heart Center, Rigshospitalet, Copenhagen, Denmark
JAMA Intern Med. 2014;174(3):336-344. doi:10.1001/jamainternmed.2013.11349.
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Importance  Clinical guidelines have been criticized for encouraging the use of β-blockers in noncardiac surgery despite weak evidence. Relevant clinical trials have been small and have not convincingly demonstrated an effect of β-blockers on hard end points (ie, perioperative myocardial infarction, ischemic stroke, cardiovascular death, and all-cause death).

Objective  To assess the association of β-blocker treatment with major cardiovascular adverse events (MACE) and all-cause mortality in patients with ischemic heart disease undergoing noncardiac surgery.

Design, Setting, Participants, and Exposure  Individuals with ischemic heart disease with or without heart failure (HF) and with and without a history of myocardial infarction undergoing noncardiac surgery between October 24, 2004, and December 31, 2009, were identified from nationwide Danish registries. Adjusted Cox regression models were used to calculate the 30-day risks of MACE (ischemic stroke, myocardial infarction, or cardiovascular death) and all-cause mortality associated with β-blocker therapy.

Main Outcomes and Measures  Thirty-day risk of MACE and all-cause mortality.

Results  Of 28 263 patients with ischemic heart disease undergoing surgery, 7990 (28.3%) had HF and 20 273 (71.7%) did not. β-Blockers were used in 4262 (53.3%) with and 7419 (36.6%) without HF. Overall, use of β-blockers was associated with a hazard ratio (HR) of 0.90 (95% CI, 0.79-1.02) for MACE and 0.95 (0.85-1.06) for all-cause mortality. Among patients with HF, use of β-blockers was associated with a significantly lower risk of MACE (HR, 0.75; 95% CI, 0.70-0.87) and all-cause mortality (0.80; 0.70-0.92), whereas among patients without HF, there was no significant association of β-blocker use with MACE (1.11; 0.92-1.33) or mortality (1.15; 0.98-1.35) (P < .001 for interactions). Among patients without HF, β-blockers were also associated with a lowered risk among those with a recent myocardial infarction (<2 years), with HRs of 0.54 (95% CI, 0.37-0.78) for MACE and 0.80 (0.53-1.21) for all-cause mortality (P < .02 for interactions between β-blockers and time period after myocardial infarction), but with no significant association in the remaining patients. Results were similar in propensity score–matched analyses.

Conclusions and Relevance  Among patients with ischemic heart disease undergoing noncardiac surgery, use of β-blockers was associated with lower risk of 30-day MACE and mortality only among those with HF or recent myocardial infarction.

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Figure 1.
Hazard Ratios Associated With β-Blockers in Different Subgroups of Patients

The effects associated with β-blockers differed in patients with and without heart failure (HF) (P < .001 for interactions between β-blockers and HF for both end points). Among the subgroup without HF, the hazard ratios associated with β-blockers were further dependent on a history of MI and time elapsed since the most recent MI (for interaction between β-blockers and MI categories, P < .001 for MACE and P = .02 for all-cause mortality). Analysis was adjusted for all variables from Table 1 plus calendar year for surgery. MACE indicates major adverse cardiovascular events (nonfatal ischemic stroke, acute myocardial infarction, and cardiovascular death); MI, myocardial infarction.

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Figure 2.
Kaplan-Meier Curves of Outcomes Associated With β-Blockers in Surgical Procedures Performed in Patients With and Without β-Blockers, Based on 1:1 Propensity Score–Matched Subgroups

C statistics of the models were 0.74 and 0.75. HF indicates heart failure; HR, hazard ratio; MACE, major adverse cardiovascular events (nonfatal ischemic stroke, acute myocardial infarction, and cardiovascular death). Baseline characteristics are available in eTables 1 and 2 in the Supplement. Patients treated with β-blockers are represented by the blue line; patients treated without β-blockers are represented by the black line.

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Figure 3.
Kaplan-Meier Curves of Outcomes of β-Blockers in Surgical Procedures Performed in Subgroups of Patients Without β-Blockers, Based on 1:1 Propensity Score–Matched Subgroups

C statistics of the models ranged from 0.75 to 0.80. MACE indicates major adverse cardiovascular events (nonfatal ischemic stroke, acute myocardial infarction, and cardiovascular death); HR, hazard ratio. Baseline characteristics are available in eTables 1 and 2 in the Supplement. Patients treated with β-blockers are represented by the blue line; patients treated without β-blockers are represented by the black line. In total, 298 patients with and 298 patients without β-blockers with a myocardial infraction (MI) of less than 2 years, 1930 patients with and 1930 patients without β-blockers with an MI of more than 2 years before the index surgery, and 2889 patients with and 2889 patients without β-blockers without an MI were included.

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