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ACC/AHA PRACTICE GUIDELINES

ACC/AHA 2006 Guideline Update on PerioperativeCardiovascular Evaluation for Noncardiac Surgery:Focused Update on Perioperative Beta-Blocker Therapy A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines(Writing Committee to Update the 2002 Guidelines on PerioperativeCardiovascular Evaluation for Noncardiac Surgery)Developed in Collaboration With (organizations to be added post approval)

WRITING COMMITTEE MEMBERSLee A. Fleisher, MD, FACC, Chair

Joshua A. Beckman, MD, FACC*Kenneth A. Brown, MD, FACC, FAHAHugh Calkins, MD, FACC, FAHAElliott Chaikof, MDKirsten E. Fleischmann, MD, MPH, FACC

William K. Freeman, MD, FACC James B. Froehlich, MD, MPH, FACCEdward K. Kasper, MD, FACC Judy R. Kersten, MD, FACCBarbara Riegel, DNSC, RN, FAHA

John F. Robb, MD, FACC#

*Society for Vascular Medicine and Biology Ofcial Representative; American Society of Nuclear Cardiology Ofcial Representative; Heart Rhythm Society OfcialRepresentative; Society for Vascular Surgery Ofcial Representative;American Society of Echocardiography Ofcial Representative; Society of Cardiovascular AnesthesiologistsOfcial Representative; #Society for Cardiovascular Angiography and Interventions Ofcial Representative

TASK FORCE MEMBERS

Sidney C. Smith, JR ., MD, FACC, FAHA, Chair Alice K. Jacobs, MD, FACC, FAHA, Vice-Chair

Cynthia D. Adams, MSN, APRN-BC, FAHA Jeffrey L. Anderson, MD, FACC, FAHAElliott M. Antman, MD, FACC, FAHA**David P. Faxon, MD, FACC, FAHAValentin Fuster, MD, PHD, FACC, FAHA, FESC Jonathan L. Halperin, MD, FACC, FAHA

Loren F. Hiratzka, MD, FACC, FAHASharon A. Hunt, MD, FACC, FAHABruce W. Lytle, MD, FACC, FAHARick Nishimura, MD, FACC, FAHARichard L. Page, MD, FACC, FAHABarbara Riegel, DNSC, RN, FAHA

**Immediate Past Chair; Former Task Force member during this writing effort

This document was approved by the American College of Cardiology FoundationBoard of Trustees in March 2006 and by the American Heart Association ScienceAdvisory and Coordinating Committee in February 2006.

When citing this document, the American College of Cardiology Foundationrequests that the following citation format be used: Fleisher LA, Beckman JA, BrownKA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB, KasperEK, Kersten JR, Riegel B, Robb JF. ACC/AHA 2006 Guideline Update onPerioperative Cardiovascular Evaluation for Noncardiac Surgery: Focused Update onPerioperative Beta-Blocker Therapy. A Report of the American College of Cardiol-ogy/American Heart Association Task Force on Practice Guidelines (Writing

Committee to Update the 2002 Guidelines on Perioperative Cardiovascular Evalua-tion for Noncardiac Surgery). American College of Cardiology Web site. Available at:http://www.acc.org/clinical/guidelines/perio_betablocker.pdf .

Copies: This document is available on the World Wide Web sites of the AmericanCollege of Cardiology ( www.acc.org) and the American Heart Association( www.my.americanheart.org). Single copies of this document are available by calling1-800-253-4636 or writing the American College of Cardiology Foundation, Re-source Center, at 9111 Old Georgetown Road, Bethesda, MD 20814-1699. Ask forreprint number 71-0362. To purchase bulk reprints specify version and reprintnumber: Up to 999 copies, call 1-800-611-6083 (U.S. only) or fax 413-665-2671;1,000 or more copies, call 214-706-1789, fax 214-691-6342, or [email protected].

Permissions: Multiple copies, modication, alteration, enhancement, and/or dis-

tribution of this document are not permitted without the express permission of theAmerican College of Cardiology Foundation. Please direct requests [email protected]

Journal of the American College of Cardiology Vol. 47, No. x, 2006 2006 by the American College of Cardiology Foundation and the American Heart Association ISSN 0735-1097/06/$32.00Published by Elsevier Inc. doi:10.1016/j.jacc.2006.02.028
http://www.acc.org/clinical/guidelines/perio_betablocker.pdfhttp://www.acc.org/clinical/guidelines/perio_betablocker.pdfhttp://www.acc.org/http://www.acc.org/http://www.my.americanheart.org/http://www.my.americanheart.org/http://[email protected]/http://[email protected]/http://[email protected]/http://[email protected]/http://[email protected]/http://www.my.americanheart.org/http://www.acc.org/http://www.acc.org/clinical/guidelines/perio_betablocker.pdf


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PREAMBLE

The American College of Cardiology/American Heart Asso-ciation (ACC/AHA) Task Force on Practice Guidelinesmakes every effort to avoid any actual, potential, or perceivedconict of interest that might arise as a result of an industry

relationship or personal interest of the writing committee.Specically, all members of the writing committee, as well aspeer reviewers of the document, were asked to provide disclo-sure statements of all such relationships that might be per-ceived as real or potential conicts of interest.These statementsare reviewed by the parent task force, reported orally to allmembers of the writing committee at each meeting, andupdated and reviewed by the writing committee as changesoccur. Please see Appendix 1 for author relationships withindustry and Appendix 2 for peer reviewer relationships withindustry.

These guidelines attempt to dene practices that meet theneeds of most patients in most circumstances. These guidelinerecommendations reect a consensus of expert opinion after athorough review of the available, current scienticevidence andare intended to improve patient care. If these guidelines areused as the basis for regulatory/payer decisions, the ultimategoal is quality of care and serving the patients best interests. The ultimate judgment regarding care of a particular patientmust be made by the healthcare provider and patient in light of all the cirucumstances presented by that patient.Sidney C. Smith Jr., MD, FACC, FAHA Chair, ACC/AHA Task Force on Practice Guidelines

Elliot M. Antman, MD, FACC, FAHA Immediate Past-Chair, ACC/AHA Task Force onPractice Guidelines

1. INTRODUCTION

1.1. Purpose of the Expedited Update

Since the publication of the previous guidelines on periopera-tive cardiovascular evaluation for noncardiac surgery in 2002,the issue of perioperative beta blockade for non-cardiac surgery has taken on increased importance. Specically, the Physicians

Consortium for Performance Improvement and the SurgicalCare Improvement Project have both identied perioperativebeta blockade as a quality measure. Given the importance of these quality measures for both public reporting and eventualpay-for-performance, and the recent series of publications onthe subject, it became imperative to update the recommenda-tions related to beta blockade. Therefore, we have chosen toexpedite the review of the literature on perioperative betablockade in order to produce recommendations that can beused in these national quality initiatives. In general, ACC/AHA Class I and III indications for therapy identify potentialdimensions of care and processes for performance measure-ment; however, not all Class I and III guidelines recommen-dations should be selected for performance measurement (1).

Furthermore, Class IIaand Class IIb recommendations are notconsidered for stand-alone measures.

Please note that the full 2002 Guideline on PerioperativeCardiovascular Evaluation for Noncardiac Surgery is beingupdated and represents current ACC/AHA policy, with theexception of the text and tables in the perioperative beta-blocker therapy section. This focused update replaces thebeta-blocker section in the 2002 Guideline and is consid-ered current ACC/AHA policy until the update of the fullguideline is published. Please note thatTable 2, ClinicalPredictors of Increased Perioperative Cardiovascular Risk,is currently under review and may be modied as part of theupdate of the full guideline.

1.2. Organization of Committee and Evidence Review The Committee to Update the 2002 Guidelines on Perioper-ative Cardiovascular Evaluation for Noncardiac Surgery: Fo-

cused Update on Perioperative Beta-Blocker Therapy reviewedthe literature relevant to perioperative cardiac evaluation sincethe last publication of these guidelines in 2002. Literaturesearches were conducted in PubMed/MEDLINE. Searches were limited to the English language, 2002 through 2006, andhuman subjects. In addition, related-article searches wereconducted in MEDLINE to nd further relevant articles.Finally, committee members recommended applicable articlesoutside the scope of the formal searches.

As a result of these searches, 23 published articles and 1abstract were identied and reviewed by the committee forthe expedited update of the Beta-Blocker section. Using

evidence-based methodologies developed by the ACC/AHA Task Force on Practice Guidelines, the committeeupdated the guideline text and recommendations.

These classes summarize the recommendations for pro-cedures or treatments as follows:

Class I: Conditions for which there is evidence forand/or general agreement that the procedure or treat-ment is benecial, useful, and effective.

Class II: Conditions for which there is conictingevidence and/or a divergence of opinion about theusefulness/efcacy of a procedure or treatment.

Class IIa: Weight of evidence/opinion is in favor of usefulness/efcacy.Class IIb: Usefulness/efcacy is less well established by evidence/opinion.

Class III: Conditions for which there is evidence and/orgeneral agreement that the procedure/treatment is notuseful/effective, and in some cases may be harmful.

In addition, the weight of evidence in support of therecommendation is listed as follows:

Level of Evidence A: Data derived from multiple,randomized, clinical trials.

Level of Evidence B: Data derived from a single-randomized trial or non-randomized studies.

2 Fleisher et al. JACC Vol. 47, No. x, 2006 ACC/AHA Perioperative GuidelineUpdate on Beta-Blocker Therapy Month 2006:000 000


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Level of Evidence C: Only consensus opinion of experts,case studies, or standard-of-care.

A recommendation with Level of Evidence B or C does notimply that the recommendation is weak. Many importantclinical questions addressed in guidelines do not lend them-selves to clinical trials. Although randomized trials are notavailable, there may be a very clear clinical consensus that aparticular test or therapy is useful and effective. The schema forclassication of recommendations and level of evidence issummarized inFigure 1, which also illustrates how the gradingsystem provides an estimate of the size of the treatment effectand an estimate of the certainty of the treatment effect.

Please note the use of bold-faced type in the recommen-dations shows where the intent of the recommendationhas changed from the 2002 ACC/AHA GuidelineUpdate on Perioperative Cardiovascular Evaluation forNoncardiac Surgery. The bold-faced type only high-

lights changes to the recommendations; it does not show changes to supporting text, tables, and gures.

The Committee consisted of acknowledged experts ingeneral cardiology as well as persons with recognizedexpertise in more specialized areas including anesthesiology,cardiovascular surgery, echocardiography, electrophysiology,interventional cardiology, nuclear cardiology, vascular med-icine, and vascular surgery; both academic and privatesectors were represented. The following organizations as-

signed ofcial representatives: the Society for VascularMedicine and Biology, American Society of Nuclear Car-diology, Heart Rhythm Society, Society for Vascular Sur-gery, American Society of Echocardiography, Society of Cardiovascular Anesthesiologists, and the Society for Car-diovascular Angiography and Interventions.

This document was reviewed by 2 ofcial reviewersnominated by the ACC; 2 ofcial reviewers nominated by the AHA; 1 ofcial reviewer from the ACC/AHA Task Force on Practice Guidelines as well as reviewers from theSociety for Vascular Medicine and Biology, American Society of Nuclear Cardiology, Heart Rhythm Society, AmericanSociety of Echocardiography, Society of CardiovascularAnesthesiologists, and the Society for Cardiovascular An-

Figure 1. Applying classication of recommendations and level of evidence.

3JACC Vol. 47, No. x, 2006 Fleisher et al.Month 2006:000000 ACC/AHA Perioperative GuidelineUpdate on Beta-Blocker Therapy


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giography and Interventions; and 20 content reviewers,including members from American College of Cardiology Foundation (ACCF) Cardiac Catheterization Committee,ACCF Peripheral Vascular Disease Committee, ACCF Cardiovascular Clinical Imaging Committee, ACCF Echo-cardiography Committee, ACCF Clinical Electrophysiol-ogy Committee, AHA Council on Cardiopulmonary Peri-operative and Critical Care Leadership Committee, AHACouncil on Cardiovascular Surgery and Anesthesia Leader-ship Committee, and the AHA Council on Clinical Car-diology, Electrocardiography, and Arrhythmias Committee.

2. PERIOPERATIVE MEDICAL THERAPY

2.1. Perioperative Beta-Blocker Therapy

Recommendations for Beta-Blocker Medical Therapy ( Table 1):

Class I

1. Beta blockers should be continued in patients undergo-ing surgery who are receiving beta-blockers to treatangina, symptomatic arrhythmias, hypertension,or other ACC/AHA Class I guideline indications.(Level of Evidence: C)

2. Beta blockers should be given to patients undergoing vascular surgery at high cardiac risk owing to the ndingof ischemia on preoperative testing.(Level of Evidence: B)

Class IIa

1. Beta blockers are probably recommended for patientsundergoing vascular surgery in whom preoperative as-sessment identies coronary heart disease.(Level of Evidence: B)

2. Beta blockers are probably recommended for patientsin whom preoperative assessment for vascular surgery identies high cardiac risk as dened by the presenceof multiple clinical risk factors.*(Level of Evidence: B)

3. Beta blockers are probably recommended for patientsin whom preoperative assessment identies coronary heart disease or high cardiac risk as dened by thepresence of multiple clinical risk factors* and who are

undergoing intermediate- or high-risk procedures asdened in these guidelines. (Level of Evidence: B)

Class IIb1. Beta blockers may be considered for patients who are

undergoing intermediate- or high-risk procedures asdened in these guidelines, including vascular sur-gery, in whom preoperative assessment identiesintermediate cardiac risk as dened by the presence of a single clinical risk factor.*(Level of Evidence: C)

2. Beta blockers may be considered in patients under-going vascular surgery with low cardiac risk (asdened in these guidelines) who are not currently on beta blockers. (Level of Evidence: C)

Class III1. Beta blockers should not be given to patients undergo-

ing surgery who have absolute contraindications to betablockade.(Level of Evidence: C)

*Please seeTable 2 , Clinical Predictors of Increased Periop-erative Cardiovascular Risk, for an explanation of theclinical risk factors. High cardiac risk includes patients witmajor and intermediate clinical predictors. Care should btaken in applying recommendations on beta-blocker therapto patients with decompensated heart failure, nonischemicardiomyopathy, or severe valvular heart disease in the

absence of coronary heart disease.2.1.1. Summary of evidence. Despite several meta-analyses, some reaching conicting conclusions, there arestill very few randomized trials of medical therapy beforenoncardiac surgery to prevent perioperative cardiac compli-cations. The studies that have been conducted in this areahave largely focused on beta-blocker therapy; however, thereremain many limitations to the available data. Few studieshave compared different beta-blocker agents or character-ized their dose effect in the perioperative setting. Even fewerhave included a protocol for the titration of therapy to effect(e.g., target heart rate), or examined regimens that include apreoperative trial of beta-blocker therapy. Studies to deter-mine the ideal target population, ideal dose, and route are

Table 1. Recommendations for Perioperative Beta-Blocker Therapy Based on Published Randomized Clinical TrialsLow CardiacPatient Risk

Intermediate CardiacPatient Risk

CHD or High CardiacPatient Risk

Patients found to have myocardial ischemia on preoperative testing

Vascular Surgery Class IIb

Level of Evidence: C

Class IIb

Level of Evidence: C

Class I

Level of Evidence: B*Class IIaLevel of Evidence: B

High-/Intermediate-Risk Surgery

Class IIbLevel of Evidence: C

Class IIaLevel of Evidence: B

Low-Risk Surgery

*Applies to patients found to have coronary ischemia on preoperative testing. Applies to patients found to have coronary heart disease. Indicates insufcient data. See text forfurther discussion.

CHD coronary heart disease.



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lacking. In addition, the practical limitations such as how, when, how long, and by whom perioperative beta-blockertherapy is ideally or practically implemented remain unad-dressed. Randomized, controlled trials are still needed toexplore the observation that there may be some harmassociated with beta-blocker therapy in low-risk patients(3). Moreover, there is currently a lack of data regarding which beta blocker to use perioperatively. Some observa-tional data suggest that perioperative death or myocardialinfarction (MI) rates may differ when different beta-blockersare given perioperatively (4). In summary, the best approach

on how to medically protect patients from cardiovascularcomplications during noncardiac surgery is still unknown.

Limitations in the Perioperative Beta-Blocker Literature:

Most trials are inadequately powered. Few randomized trials of medical therapy to prevent

perioperative major adverse cardiac events have beenperformed.

Few randomized trials have examined titration of therapy to effect (e.g., target heart rate).

Few randomized trials have examined the role of periop-erative beta-blocker therapy.

Studies to determine the role of beta blockers inintermediate- and low-risk populations are lacking.

Studies to determine the optimal type of beta blockers arelacking.

No studies have addressed care-delivery mechanisms inthe perioperative setting, identifying how, when, and by whom perioperative beta-blocker therapy should be im-plemented and monitored.

Although many of the randomized, controlled trials of beta-blocker therapy are small, the weight of evidenceespecially in aggregatesuggests a benet to perioperativebeta blockade during noncardiac surgery, particularly inhigh-risk patients. Current studies suggest that beta block-ers reduce perioperative ischemia and may reduce the risk of MI and death in high-risk patients. When possible, avail-able evidence suggests, but does not denitively prove thatbeta blockers should be started several days or weeks beforeelective surgery, with the dose titrated to achieve a restingheart rate between 50 and 60 beats per min, to assure that

the patient is indeed receiving the benet of beta blockadeand should continue during the intraoperative and postop-erative period to maintain a heart rate less than 80 beats permin (5). Several prospective, randomized trials are eitherunderway or soon to be presented. These will hopefully shedlight on some of the questions regarding perioperativebeta-blocker therapy. Per the ACC/AHA Task Force onPractice Guidelines methodology, unpublished data cannotbe used to formulate guideline recommendations.

Two randomized trials examined the effect of periopera-tive beta blockers on cardiac events surrounding surgery.Poldermans et al. (5) examined the effect of bisoprolol on

patients undergoing vascular surgery and in patients athigh-risk for perioperative cardiac complications scheduledfor vascular surgery. Of 846 patients with risk factors forcardiac disease, 173 patients were found to have new regional wall motion abnormalities (RWMA) on dobut-amine stress echocardiogram (DSE). Of these patients, 61 were excluded from further study owing to large areas(greater than or equal to 5 segments) of RWMA on DSE orbecause they were already taking beta blockers. The remain-ing 112 high-risk patients were randomized to standard careor bisoprolol started at least 7 days preoperatively andtitrated to maintain heart rate less than 60 beats per minpreoperatively and less than 80 beats per min intraopera-tively and postoperatively. The rates of cardiac death (3.4% vs. 17%;p 0.02) and nonfatal MI (0% vs. 17%;p less thanor equal to 0.001) were lower for the bisoprolol versusplacebo groups, respectively. Importantly, due to the un-blinded design and inclusion of only high-risk patients inthis study, the results cannot be generalized to all patientsundergoing noncardiac surgery.

Boersma et al. (6) subsequently re-analyzed the total cohortof 1,351 consecutive patients considered for enrollment in theaforementioned randomized trial of bisoprolol. Forty-ve pa-tients had perioperative cardiac death or nonfatal MI. A totalof 83% of patients had fewer than three clinical risk factors.Among this subgroup, patients receiving beta blockers had a

Table 2. Clinical Predictors of Increased PerioperativeCardiovascular Risk (Myocardial Infarction, Heart Failure,Death)Major Unstable coronary syndromes Acute or recent MI* with evidence of important ischemic risk by

clinical symptoms or noninvasive study Unstable or severe angina (Canadian Class III or IV)Decompensated heart failureSignicant arrhythmias High-grade atrioventricular block Symptomatic ventricular arrhythmias in the presence of underlying

heart disease Supraventricular arrhythmias with uncontrolled ventricular rateSevere valvular diseaseIntermediateMild angina pectoris (Canadian Class I or II)Previous MI by history or pathological Q wavesCompensated or prior heart failureDiabetes mellitus (particularly insulin-dependent)Renal insufciency

Minor Advanced ageAbnormal ECG (left ventricular hypertrophy, left bundle-branch block,

ST-T abnormalities)Rhythm other than sinus (e.g., atrial brillation)Low functional capacity (e.g., inability to climb one ight of stairs with

a bag of groceries)History of strokeUncontrolled systemic hypertension

*The American College of Cardiology National Database Library denesrecent MI asgreater than 7 days but less than or equal to 1 month (30 days); acute MI is within7 days. May include stable angina in patients who are unusually sedentary.Campeau et al. (2).

ECG electrocardiogram; MI myocardial infarction.



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lower risk of cardiac complications (0.8% [2 of 263]) than thosenot receiving beta blockers (2.3% [20 of 855]). In patients withthree or more risk factors (17%), those taking beta blockers who had a DSE demonstrating four or fewer segments of new wall-motion abnormalities had a signicantly lower incidenceof cardiac complications (2.3% [2 of 86]) compared with thosenot receiving beta-blocker therapy (9.9% [12 of 121]). How-ever, among the small group of patients with more extensiveischemia on DSE (ve or more segments), there was nodifference in the incidence of cardiac events (4 of 11 for thosetaking beta blockers versus 5 of 15 for those not taking betablockers). Therefore, beta-blocker therapy was benecial in allbut the subset of patients with more extensive ischemia.Nevertheless, one must be cautious about inferring a class effectfrom this observation about bisoprolol and treatment protocol.

The Multicenter Study of Perioperative Ischemia (McSPI)research group (7,8) reported on 200 patients undergoinggeneral surgery randomized to a combination of intravenousand oral atenolol versus placebo for seven days. Althoughthey found no difference in perioperative MI or death, they reported signicantly fewer episodes of ischemia by Holtermonitoring (24% vs. 39%;p 0.03) in the atenolol versusplacebo groups, respectively. They then followed thesepatients after discharge and documented fewer deaths in theatenolol group over the subsequent 6 months (1% vs. 10%; p less than 0.001). It is not clear why such a brief course of therapy could exert such a delayed effect, and the study didnot control for other medications given either before or aftersurgery. Angiotensin-converting enzyme inhibitor and beta-blocker use preoperatively differed signicantly between thestudy groups.

Additional studies have examined the use of perioperativebeta blockers, but are limited in power to detect cardiac eventsor are not randomized. Stone et al. (9) randomized a group of patients with mild hypertension who underwent predomi-nantly (58%) vascular surgery to oral beta blockers 2 hoursbefore surgery or standard care. Control subjects had a higherfrequency (28%) of ST-segment depression (on intraoperativemonitoring, as reported by the authors) than treated patients(2%). In a nonrandomized study, Pasternack et al. (10) gaveoral metoprolol immediately before surgery, followed postop-eratively by intravenous metoprolol during abdominal aorticaneurysm repair. Only 3% suffered an acute MI compared with18% for matched controls. Pasternack et al. (11) subsequently reported fewer episodes of intraoperative ischemia in patientstreated with oral metoprolol before peripheral vascular surgery compared to untreated patients. Yeager et al. (12) reported acase-control analysis of their experience with perioperative MIduring vascular surgery, comparing 53 index cases of periop-erative MI with 106 matched controls. They found a strongassociation of beta-blocker use with a decreased likelihood of MI (odds ratio 0.43;p 0.01). Raby et al. (13) demonstratedin 26 vascular surgery patients with documented preoperativeischemia and randomized to a protocol of heart rate suppres-sion with intravenous esmolol compared to standard care thatthe esmolol group had fewer episodes of ischemia than controls

(33% vs. 72%; p 0.055). Zaugg et al. (14) randomized elderly noncardiac surgery patients to preoperative and postoperativeatenolol titrated to heart rate and intraoperative atenololtitrated to heart rate or no beta blockers, and detected noepisodes of intraoperative myocardial ischemia, electrocardio-graphic changes consistent with MI, or death in any group. Three (of 19) patients in the no beta-blocker group developedsignicant elevations of cardiac troponin-I consistent with aperioperative MI compared with 0 (of 40) patients whoreceived one of the atenolol groups. Brady et al. (15) random-ized patients undergoing elective vascular surgery to eithermetoprolol 50 mg twice per day or placebo, from admission tohospital, until 7 days postoperatively. They found no differencein cardiovascular events, which included MI, unstable angina, ventricular tachycardia, and stroke. This trial may have beenunderpowered (n 103) to identify a difference in outcomes,particularly hard outcomes of death and MI. Also, by trialdesign, therapy was initiated the day before vascular surgery,and it is quite possible that those randomized to metoprololreceived incomplete beta-blockade in the early perioperativeperiod.

Perioperative beta-blocker therapy has been reviewed inseveral meta-analyses, and in a very large cohort populationstudy. Auerbach and Goldman (16) undertook a review of thistopic in 2002. They reported on a MEDLINE search andliterature review of only ve studies. (All ve studies areincluded in Table 3). They calculated a number needed totreat, on the basis of these studies, of only 2.5 to 6.7 to seeimprovement in measures of myocardial ischemia, and only 3.2to 8.3 in studies reporting a signicant impact of beta blockerson cardiac or all-cause mortality. They concluded that theliterature supports a benet of beta blockers on cardiacmorbidity.

A systematic review of the perioperative medical therapy literature by Stevens et al. (17) for noncardiac surgery included the results of 11 trials using beta blockers forperioperative therapy. These authors concluded that beta-blockers signicantly decreased ischemic episodes duringand after surgery. Beta blockers signicantly reduced therisk of nonfatal MI; however, the results became nonsignif-icant if the two most positive trials were eliminated. Like- wise, the risk of cardiac death was signicantly decreased with beta-blocker usage. It should be noted that theseauthors incorporated studies not considered in other meta-analyses, including studies that were not blinded. Results tobe quantied were limited to those in the 30-day perioper-ative period. The authors also reported a direct relationshipbetween the prevalence of prior MI and the magnitude of risk reduction observed with beta-blocker therapy, suggest-ing that higher risk confers greater benet. The numberneeded to prevent perioperative ischemia was 8 patients, thenumber needed to prevent MI was 23, and 32 subjects mustbe treated to prevent cardiac death. These authors point outthat, given the observation that high-risk patients seem toreceive all the benet, the target population for beta-blockertherapy is not clear. They also highlighted that schedules of



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beta-blocker administration varied signicantly among thereported studies and the potential for a single large strongly positive study to skew the results of this meta-analysis.

In contrast, Devereaux et al. (18) published their opinionpaper on the clinical evidence regarding the use of beta-blockertherapy in patients undergoing noncardiac surgery for thepurpose of preventing perioperative cardiac complications. They expressed the opinion that the literature supporting useof beta blockers during noncardiac surgery is modest at best,based on a few small, unblinded studies with a focused patientpopulation. In a review of the literature in 2005, Devereaux etal. (19) discussed 22 studies randomizing 2,437 patients un-dergoing noncardiac surgery to beta-blocker therapy or pla-cebo. The POBBLE study was not included in this review (14). They found no statistically signicant benet on any of the individual outcomes, and a nominally statistically sig-nicant benet (relative risk of 0.44 with 95% condenceinterval [CI] 0.20 to 0.97, 99% CI 0.16 to 1.24) for thecomposite outcome of cardiovascular mortality, nonfatalMI, and nonfatal cardiac arrest. The authors felt these data were inadequate to draw conclusions, and that a larger,controlled study is indicated before conclusions can bemade. This review, however, included a wide variety of studies, patient populations, and beta-blocker regimens.Many of the studies described only a single or double doseof beta blocker preoperatively or at induction of anesthesia.Much of the data, therefore, does not pertain to perioper-ative beta blockade for the purpose of cardiac risk reductionor focused on a low-risk population. Additionally, thelargest studies includedthose reported by Miller et al. (20)and preliminary data from Yang et al. (21), which togetheraccount for almost as many subjects as all other studiescombinedmay not have been appropriate to include inthis analysis. The rst, by Miller et al. (20), was a study of a single intravenous dose of beta blocker for the purpose of blood pressure control during intubation, not reduction of perioperative events. It included follow-up only to the pointof discharge from the recovery room. The second, that of Yang et al. (21), has yet to be published and, therefore, hasnot undergone formal peer review. The studies included inthis review also vary widely in length of follow-up.

McGory et al. (22) performed a meta-analysis of six ran-domized trials of perioperative beta-blockade and concludedthat therapy was associated with signicant reductions inperioperative myocardial ischemia (33% to 15%), MI, cardiacmortality, and long-term cardiac mortality (12% to 2%). Theseauthors used the combined data to derive odds ratios and CIsfor several outcomes. For perioperative overall mortality theodds ratio for beta-blocker therapy was 0.52 (95% CI 0.20 to1.35) and for perioperative cardiac mortality odds ratio 0.25(95% CI 0.07 to 0.87). Neither the POBBLE study nor theunpublished ndings included in the Devereaux et al. (19)paper were included, explaining the marked difference inndings from the other meta-analysis.

A cohort study by Lindenauer et al. (23) reviewed recordsfrom over 700,000 patients undergoing noncardiac surgery at

329 hospitals in the U.S. Participant hospitals in this cohortstudy were members of a consortium database measuringquality and health care use. These authors evaluated allnoncardiac surgical cases, and compared those who receivedbeta blockers within the rst two days of hospitalization withthose who did not receive beta blockers during the rst twohospital days. The authors used propensity score matchingtechniques in an attempt to reduce bias. These authors foundthat for a revised cardiac risk index score (24) of three or more(based on the presence of history of ischemic heart disease,cerebrovascular disease, renal insufciency, diabetes mellitus, ora patient undergoing high-risk surgery), patients who receivedbeta blockers were signicantly less likely to die in hospital. This was not true for those with a revised risk index of 2, l, or0. Those with a risk index of 0 were more likely to diein-hospital if given a beta blocker on day 1 or day 2 of hospitalization. This study is retrospective and not randomizedand, therefore, is subject to potential bias. This is particularly true in terms of reporting bias as the documentation was basedentirely on administrative datasets, using arbitrary denitionsof on or off perioperative beta blockers, based solely onhospital day of use. Nonetheless, there appears to be anassociation between improved outcomes and the use of betablockers in clinically high-risk patients.

Finally, one recent observational cohort study examined thequestion of which beta blocker may be best for perioperativemedical therapy. Redelmeier et al. (4) reviewed administrativedata related to elective surgery in Ontario, Canada, anddocumented perioperative beta-blocker usage from April 1992to April 2002 (10 years). They limited their analysis to patientsover the age of 65 years, who were receiving either atenolol ormetoprolol before and after surgery and identied 37,151subjects. A total of 1,038 suffered either a perioperative MI ordeath, and the rate of MI or death was signicantly loweramong those patients receiving atenolol versus metoprolol(2.5% vs. 3.2%,p less than 0.001). This difference persistedeven after adjusting for demographic, clinical, and surgicalfactors. The inclusion of other long-acting beta blockers in theanalysis yielded an identical risk reduction. These data suggestthat long-acting beta blockade (when therapy is initiated beforesurgery), may be superior to short-acting beta blockade. Theseobservations await clinical trial evaluation.

REFERENCES

1. Spertus JA, Eagle KA, Krumholz HM, et al. American College of Cardiology and American Heart Association methodology for theselection and creation of performance measures for quantifying thequality of cardiovascular care. J Am Coll Cardiol 2005;45:114756.

2. Campeau L. Grading of angina pectoris (letter). Circulation 1976;54:5223.

3. Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B,Benjamin EM. Perioperative beta-blocker therapy and mortality aftermajor noncardiac surgery. N Engl J Med 2005;353:349 61.

4. Redelmeier D, Scales D, Kopp A. Beta-blockers for elective surgery inelderly patients: population based, retrospective cohort study. BMJ2005;331:932.

5. Poldermans D, Boersma E, Bax JJ, et al. The effect of bisoprolol onperioperative mortality and myocardial infarction in high-risk patientsundergoing vascular surgery. Dutch Echocardiographic Cardiac Risk



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Evaluation Applying Stress Echocardiography Study Group (seecomments). N Engl J Med 1999;341:178994.

6. Boersma E, Poldermans D, Bax JJ, et al. Predictors of cardiacevents after major vascular surgery: role of clinical characteristics,dobutamine echocardiography, and beta-blocker therapy. JAMA2001;285:186573.

7. Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol onmortality and cardiovascular morbidity after noncardiac surgery. Mul-ticenter Study of Perioperative Ischemia Research Group (see com-ments) (published erratum appears in N Engl J Med 1997;336:1039).N Engl J Med 1996;335:171320.

8. Wallace A, Layug B, Tateo I, et al. Prophylactic atenolol reducespostoperative myocardial ischemia. McSPI Research Group (see com-ments). Anesthesiology 1998;88:717.

9. Stone JG, Foex P, Sear JW, Johnson LL, Khambatta HJ, Triner L.Myocardial ischemia in untreated hypertensive patients: effect of asingle small oral dose of a beta-adrenergic blocking agent. Anesthesi-ology 1988;68:495500.

10. Pasternack PF, Imparato AM, Baumann FG, et al. The hemodynam-ics of beta-blockade in patients undergoing abdominal aortic aneurysmrepair. Circulation 1987;76:III17.

11. Pasternack PF, Grossi EA, Baumann FG, et al. Beta-blockade todecrease silent myocardial ischemia during peripheral vascular surgery.Am J Surg 1989;158:1136.

12. Yeager RA, Moneta GL, Edwards JM, Taylor LM Jr., McConnellDB, Porter JM. Reducing perioperative myocardial infarction follow-ing vascular surgery. The potential role of beta-blockade. Arch Surg1995;130:86972.

13. Raby KE, Brull SJ, Timimi F, et al. The effect of heart rate control onmyocardial ischemia among high-risk patients after vascular surgery (see comments). Anesth Analg 1999;88:47782.

14. Zaugg M, Tagliente T, Lucchinetti E, et al. Benecial effects frombeta-adrenergic blockade in elderly patients undergoing noncardiacsurgery. Anesthesiology 1999;91:167486.

15. Brady AR, Gibbs JS, Greenhalgh RM, Powell JT, Sydes MR.Perioperative beta-blockade (POBBLE) for patients undergoing in-

frarenal vascular surgery: results of a randomized double-blindcontrolled trial. J Vasc Surg 2005;41:6029.

16. Auerbach AD, Goldman L. Beta-blockers and reduction of cardiacevents in noncardiac surgery: scientic review. JAMA 2002; 87:143544.

17. Stevens RD, Burri H, Tramer MR. Pharmacologic myocardial pro-tection in patients undergoing noncardiac surgery: a quantitativesystematic review. Anesth Analg 2003; 7:62333.

18. Devereaux PJ, Yusuf S, Yang H, Choi PT, Guyatt GH. Are therecommendations to use perioperative beta-blocker therapy in patientsundergoing noncardiac surgery based on reliable evidence? CMAJ2004;171:2457.

19. Devereaux PJ, Beattie WS, Choi PT, et al. How strong is the evidencefor the use of perioperative beta-blockers in non-cardiac surgery?Systematic review and meta-analysis of randomised controlled trials.BMJ 2005;331:31321.

20. Miller DR, Martineau RJ, Wynands JE, Hill J. Bolus administration of esmolol forcontrollingthe haemodynamicresponse to trachealintubation:theCanadian Multicentre Trial. Can J Anaesth 1991;38:84958.

21. Yang H, Raymer K, Butler R, Parlow J, Roberts R, Tech M. Metoprololafter Vascular Surgery (MaVS) (abstr). Can J Anaesth 2004;51:A7.

22. McGory ML, Maggard MA, Ko CY. A meta-analysis of perioperativebeta-blockade: what is the actual risk reduction? Surgery 2005;138:1719.

23. Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B,Benjamin EM. Perioperative beta-blocker therapy and mortality aftermajor noncardiac surgery. N Engl J Med 2005;353:349 61.

24. Lee TH, Marcantonio ER, Mangione CM, et al. Derivation andprospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:10439.

25. Urban MK, Markowitz SM, Gordon MA, Urquhart BL, Kligeld P.Postoperative prophylactic administration of beta-adrenergic blockersin patients at risk for myocardial ischemia. Anesth Analg 2000;90:125761.

APPENDIX 1. Author Relationships With Industry for the ACC/AHA Guideline Update on PerioperativeCardiovascular Evaluation for Noncardiac Surgery: Focused Update on Perioperative Beta-Blocker Therapy

Committee Member Consultant Research GrantScientic

Advisory Board Speakers Bureau Other

Joshua A. Beckman, MD Bristol-Myers Squibb None Sano-Aventis Bristol-Myers Squibb Merck Eli Lilly Sano-Aventis

None

Kenneth A. Brown, MD None None None None None

Hugh Calkins, MD None None None None None

Elliott Chaikof, MD None None None None None

Kirsten E. Fleischmann,MD, MPH None None None None

Pzer (QI/CMEInitiatives)

Lee A. Fleisher, MD None None None None None

William K. Freeman, MD None None None None None

James B. Froehlich, MD,MPH

Pzer None Sano-Aventis Sano-Aventis Otsuka Pzer Merck

None

Edward K. Kasper, MD None None None None None

Judy R. Kersten, MD Abbott Laboratories Abbott Laboratories None Abbott Laboratories

Barbara Riegel, DNSc, RN None None None None None

John F. Robb, MD None None None None None



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APPENDIX 2. External Peer Reviewer Relationships With Industry for the ACC/AHA Guideline Update onPerioperative Cardiovascular Evaluation for Noncardiac Surgery: Focused Update on Perioperative Beta-Blocker Therapy *

Peer Reviewer Representation Research GrantSpeakers

Bureau/Honoraria Stock OwnershipConsultant/

Advisory Board Other

Dr. Peter Alagona Ofcial ReviewerBoard of Trustees(BOT)

None None None None None

Dr. Joseph Alpert Ofcial ReviewerAHA Reviewer


Dr. Vincent Carr Ofcial ReviewerBoard of Governors (BOG)


Dr. Ray Gibbons Ofcial ReviewerAHA Reviewer

Radiant Medical Boston Scientic Boehringer Ingelheim Spectranetrics KAI Pharmaceuticals TargeGen TherOx

King Pharmaceuticals

None None Hawaii Biotech Cardiovascular

Clinical Studies(WOMENstudy, TIMI37 A)

Consumers

Union

None

Dr. Bruce Lytle Ofcial ReviewerACCF/AHA Task ForcePractice Guidelines

None None Johnson & Johnson None None

Dr. SusanBegelman

OrganizationalReviewerSociety for VascularMedicine andBiology (SVMB)

None Bristol-Myers Squibb Sano-Aventis GlaxoSmithKline

None Bristol-MyersSquibb

Sano-Aventis GlaxoSmithKline

None

Dr. Simon Body OrganizationalReviewerSociety of CardiovascularAnesthesiologists(SCA)

Content ReviewerAHA Council onCardiopulmonary,Perioperative andCritical care


Dr. Bengt Herweg OrganizationalReviewerHeartRhythm Society (HRS)


Dr. Scott Kinlay OrganizationalReviewerSociety for VascularMedicine andBiology (SVMB)

Pzer Pzer Merck

None Pzer None

Dr. Richard Page OrganizationalReviewerHeart

Rhythm Society (HRS) Content Reviewer-

ACCF ClinicalElectrophysiology Committee

Content ReviewerAHA Council onClinical Cardiology Electrocardiography and ArrhythmiasCommittee

None None None Procter andGamble

Pharmaceuticals

None

Dr. Mark Turco OrganizationalReviewerSociety for CardiovascularAngiography andInterventions

(SCAI)

None Boston ScienticCorp.

Medtronic

None BostonScientic Corp.

Medtronic

None

Continued on next page



11/12

APPENDIX 2 Continued




Dr. Neil Weissman OrganizationalReviewerAmericanSociety of

Echocardiography (ASE)

Edwards LifeSciences

Carbomedics

Wyeth Bristol-Myers SquibbMedical Imaging

Cook Corp. Boston Scientic Arbor Surgical Arena Pharmaceutical Mitsubishi

None None Wyeth Pzer Bristol-Myers

Squibb MedicalImaging Boston

Scientic

None

Dr. Kim Williams OrganizationalReviewerAmericanSociety of NuclearCardiology (ASNC)

Content ReviewerACCF CardiovascularClinical Imaging

Committee

Bristol-Myers Squibb CV Therapeutics

GE Healthcare Astellas Pharma

None GE Healthcare KingPharmaceuticals(Expert Reader)

Dr. Mazen Abu-Fadel

Content ReviewerACCF CardiacCatheterizationCommittee


Dr. Ralph Bolman Content ReviewerAHA Council onCardiovascularSurgery andAnesthesia


Dr. Mark Carlson Content ReviewerACCF ClinicalElectrophysiology Committee

None Medtronic AtriCure, Inc. St. Jude Guidant

None

Dr. Leslie Cho Content ReviewerACCF PeripheralVascular DiseaseCommittee

Bristol-Myers Squibb Aventis-Sano

Bristol-Myers Squibb Aventis-Sano

None None None

Dr. Jose Diez Content ReviewerACCF CardiacCatheterizationCommittee


Dr. J. KevinDonahue



Dr. LeonardDreifus

Content ReviewerACCF Clinical

Electrophysiology Committee

None None None Merck None

Dr. N.A. Mark Estes


None Medtronic Guidant St. Jude Medical

None Medtronic None

Dr. A. MarcGillinov

Content ReviewerAHA Council onCardiovascularSurgery andAnesthesia

None Edwards LifeSciences

None AtriCure, Inc. None

Continued on next page



12/12

APPENDIX 2 Continued




Dr. Loren Hiratzka Content ReviewerAHA Council onCardiovascular

Surgery andAnesthesia


Dr. Lawrence Katz Content ReviewerACCF Echocardiography Committee


Dr. Smadar Kort Content ReviewerACCF Echocardiography Committee


Dr. Peter Kowey Content ReviewerACCF ClinicalElectrophysiology Committee


Dr. Fred Krainin Content ReviewerACCF CardiacCatheterizationCommittee

None None Boston Scientic Johnson & Johnson Medtronic

None None

Dr. ChristopherKramer

Content ReviewerACCF CardiovascularClinical ImagingCommittee

Astellas Novartis

GE Healthcare None GE Healthcare Novartis

SiemensMedicalSolutions(ResearchSupport)

Dr. Jerrold Levy Content ReviewerAHA Council onCardiovascularSurgery andAnesthesia

None None None Bayer Dyax

AlexionPharmaceuticals(SteeringCommittee forpexellizumab)

Novo Nordisk FXIII (SteeringCommittee forFXIII)

Dr. M. SeanMcMurry

Content ReviewerAHA Council onCardiopulmonary,Perioperative andCritical Care


Dr. Charanjit Rihal Content ReviewerACCF CardiacCatheterizationCommittee

Cardiac Dimensions None None Millennium None

Dr. Carlos Ruiz Content ReviewerACCF CardiacCatheterizationCommittee


Dr. Frank Sellke Content ReviewerAHA Council onCardiovascularSurgery andAnesthesia

None Bayer Corporation None CereMedix Inotek

Corporation

None

Dr. Janet Wyman Content ReviewerACCF CardiacCatheterizationCommittee


This table represents the relationships of peer reviewers with industry that were disclosed at the time of peer review of this guideline. It does not necessarily reect relationship with industry at the time of publication. *Participation in the peer review process does not imply endorsement of the document. Names are listed in alphabetical order withincategory of review.


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