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BetaBlockers and Reduction of Cardiac Events in Noncardiac Surgery Christine Dehlendorf, MD Journal

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Title: BetaBlockers and Reduction of Cardiac Events in Noncardiac Surgery Christine Dehlendorf, MD Journal


1
Beta-Blockers and Reduction of Cardiac Events in
Noncardiac SurgeryChristine Dehlendorf,
MDJournal ClubNovember 13, 2002
2
Context
  • 30 million patients per year have non-cardiac
    surgery, and 3 million of these have or are at
    risk for having cardiovascular disease
  • Concern for cardiovascular disease the most
    common reason for pre-operative consultation
  • Consultations often limited to
  • Estimation of risk
  • Postponing or canceling surgery
  • Consideration of revascularization

3
Managing the Risk The rationale for using
beta-blockers peri-operatively
  • Studies have found post-operative ischemia to
    increase subsequent myocardial events up to 28
    fold.
  • Post-operative ischemia estimated to occur in
    25-50 of at risk patients.
  • May be related to elevated heart rate found
    post-operatively.

4
Relevance to the Family Physician
  • Important role in pre-operative evaluations
  • Managing pre and post-operative inpatients

5
Beta-Blockers and Reduction of Cardiac Events in
Noncardiac SurgeryAD Auerbach and L Goldman.
JAMA 20022871435-1444.
  • Scientific review of RCT data on peri-operative
    beta blocker use.
  • Five studies from 1988 to 2000.
  • Total of less than 600 patients.
  • Very heterogenous data sources.

6
Review of Studies
7
Results of the Review
  • 3 out of 4 studies found a decrease in
    peri-operative ischemia in beta-blocker treated
    patients.
  • NNT 2.5-6.7.
  • 2 out of 3 studies found a decrease in cardiac
    death in beta blocker treated patients.
  • NNT 3.2-12.7.
  • Size of effect varied by risk status of study
    population, with largest effect in patients with
    abnormal dobutamine echocardiograms.

8
Effect of Atenolol on Mortality and
Cardiovascular Morbidity After Non-Cardiac
SurgeryMangano et al. NEJM 19963351713-20.
  • Randomized, double blind, placebo controlled
    trial
  • 200 patients enrolled, 192 followed for two
    years.
  • Received IV atenolol 30 minutes prior to and
    after surgery, then transitioned to oral dosing.
  • Monitored during hospitalization and had six
    month, one year and two year evaluations.

9
Patient Selection
  • Patients with or at risk for CAD at SF VAMC
    undergoing elective noncardiac surgery with GETA
  • Previous MI, typical angina, or atypical angina
    with positive stress test
  • OR
  • Two or more of the following risk factors
  • gt 65 yo, hypertension, smoking, cholesterol gt240
    mg/dl, and diabetes.
  • Exclusion criteria left BBB, pacemaker, ST-T
    wave abnormalities limiting ECG interpretation.

10
Characteristics of Patients by Study Group
11
Outcomes
  • Principle effect on mortality seen at 6-8 months,
    with 9 3,15 ARR, NNT 11.
  • Benefit maintained up to two years, with 12
    7,17 ARR for death at end of follow-up
    period, 8 4, 12 ARR for death from cardiac
    causes.
  • Atenolol treated group with 16 10, 22 ARR
    for cardiac events at 2 years, NNT 6.

12
Outcomes, Continued
  • Companion study found 40 lower incidence of
    ischemic events in seven days post-operative, but
    no difference in events pre- and
    intra-operatively.
  • More than 85 tolerated study drug, and 60 were
    able to receive the full dose
  • No difference in incidence of bradycardia,
    hypotension or bronchospasm between study groups.

13
Potential Confounders
  • Atenolol group was more likely to be taking
    beta-blockers (14 vs. 7) and ACE inhibitors
    (20 vs. 6) at discharge.
  • Odds ratio for mortality at two years associated
    with use of these two drugs were not significant.
  • However, it is unclear if these variables were
    included in the statistical modeling of
    predictors of death.

14
Potential Confounders, Continued
  • Statistics suggest treatment effect may only be
    seen in patients with diabetes.
  • Increased treatment effects seen in patients with
    DM (hazard ratio for pts with DM 0.25 compared to
    0.4 for all patients).
  • Atenolol effect no longer significant when
    controlled for DM in multivariable analysis.

15
Conclusions
  • Authors conclude that perioperative beta blockade
    is safe and effective in preventing mortality and
    cardiovascular events in patients with or at risk
    for CAD.
  • Rough estimate of cost, based on 1/5th of effect
    seen in this study, cost is 2,500 per life-year
    saved.

16
Critique of Study
  • Effect of potential confounders unclear
  • Diabetes
  • Use of anti-hypertensive medications
  • What variables were tested in the statistical
    model not stated.
  • Gender of patients not discussed.
  • Small sample size, with potential for
    non-significant differences in groups to have a
    confounding effect.

17
JAMA Review Summary Recommendations
  • While evidence exists to support use of
    beta-blockers perioperatively, there are
    substantially gaps in the data
  • Only five heterogenous RCTs with fewer than 600
    patients support this finding.
  • Data is limited in patients with depressed
    ejection fraction or undergoing regional
    anesthesia or conscious sedation.
  • Effect of beta blockers in low risk patients
    unknown.
  • Best treatment regimen unclear, with no evidence
    one agent superior.
  • Do recommend starting 30 days before and
    continuing after surgery, with IV administration
    titrated immediately prior to surgery.

18
Recommendations, Continued
  • Recommend differentiating low, intermediate and
    high risk groups based on clinical
    characteristics.
  • See Figure on p. 1441
  • Use of beta-blockers increases threshold for
    further testing to those with greater than 3 risk
    criteria or 1-2 and poor functional status.
  • Intermediate risk with good functional status can
    have surgery with beta blockade.
  • Low risk patients most likely do not benefit from
    beta blockade.

19
The Next Steps
  • Need larger RCT looking at effect on cardiac
    outcomes of perioperative beta blocker use across
    cardiac risk profiles.
  • If data continues to support its use, need to
    define ideal dosing regimen.
  • Need to incorporate data into existing
    peri-operative risk management algorithms.
  • In meantime, we may chose to forgo further
    testing in some patients who are candidates for
    beta blockers.

20
Selected References
  • Auerbach AD, Goldman L. Beta blockers and
    reduction of cardiac events in noncardiac
    surgery. JAMA 20022871435-44.
  • Boersma E, Poldermans D, Bax JJ, et al.
    Predictors of cardiac events after major vascular
    surgery Role of clinical characteristics,
    dobutamine echocardiograph and beta blocker
    therapy. JAMA 20012851865-1873.
  • Eagle KA. ACC/AHA guideline update for
    perioperative cardiovascular evaluation for
    non-cardiac surgery a report of the American
    College of Cardiology/American Heart Association
    Task Force on Practice Guidelines. 2002. American
    College of Cardiology website, www.acc.org/clnical
    /guidelines/perio/dirindex.htm.
  • Lee TH et al. Derivation and prospective
    Validation of a simple index for prediction of
    cardiac risk of major non-cardiac surgery.
    Circulation 19991001043-49.
  • Mangano DT et al. Effect of atenolol on mortality
    and cardiovascular morbidity after non-cardiac
    surgery. NEJM 19963351713-20.
  • Mangano DT et al. Association of perioperative
    ischemia with cardiac morbidity and mortality in
    men undergoing non-cardiac surgery. NEJM
    19903231781-8.
  • Wallace et al. Prophylactic atenolol reduces
    postoperative myocardial ischemia. Anesthesiology
    1998887-17.
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