The effects of perioperative β-blockade: Results of the Metoprolol after Vascular Surgery (MaVS) study, a randomized controlled trial

doi:10.1016/j.ahj.2006.07.024

American Heart Journal

Volume 152, Issue 5, November 2006, Pages 983-990

https://doi.org/10.1016/j.ahj.2006.07.024 Get rights and content

Background

Patients undergoing vascular surgery comprise the highest risk group for perioperative cardiac mortality and morbidity after noncardiac procedures. Many current guidelines recommend the use of β-blockers in all patients undergoing vascular surgery. We report a trial of the perioperative administration of metoprolol and its effects on the incidence of cardiac complications at 30 days and 6 months after vascular surgery.

Methods

Patients undergoing abdominal aortic surgery and infrainguinal or axillofemoral revascularizations were recruited to a double-blind randomized controlled trial of perioperative metoprolol versus placebo. Patients were randomized to receive study medication, starting 2 hours preoperatively until hospital discharge or maximum of 5 days postoperatively. Primary outcome were postoperative 30-day composite incidence of nonfatal myocardial infarction, unstable angina, new congestive heart failure, new atrial or ventricular dysrhythmia requiring treatment, or cardiac death.

Results

Patients were randomized to receive either metoprolol (n = 246) or placebo (n = 250). Primary outcome events at 30 days postoperative occurred in 25 (10.2%) versus 30 (12.0%) (P = .57) in metoprolol and placebo groups, respectively (relative risk reduction 15.3%, 95% CI −38.3% to 48.2%). Observed effects at 6 months were not significantly different (P = .81) (relative risk reduction 6.2%, 95% CI% −58.4% to 43.8%). Intraoperative bradycardia requiring treatment was more frequent in the metoprolol group (53/246 vs 19/250, P = .00001), as was intraoperative hypotension requiring treatment (114/246 vs 84/250, P = .0045).

Conclusion

Our results showed metoprolol was not effective in reducing the 30-day and 6-month postoperative cardiac event rates. Prophylactic use of perioperative β-blockers in all vascular patients is not indicated.

Section snippets

Study population

The study was conducted in 3 tertiary care centers in Canada: General Campus, Hamilton Health Sciences; Victoria Campus, London Health Sciences; and Kingston General Hospital between 1999 and 2002. After approval from the Research Ethics Boards, all patients undergoing vascular surgery were screened for eligibility. Elective vascular surgical patients are evaluated by internists, cardiologists, or anesthesiologists in preoperative clinics. Screening was also undertaken on the wards when

Results

We screened 2847 patients (Figure 1), of whom 2024 met the inclusion criteria. Patients were excluded for ≥1 of the following: current β-blocker use, 638 (31.5%); airflow obstruction, 283 (14.0%); history of CHF, 149 (7.4%); atrioventricular heart block, 99 (5.0%); previous participation in MaVS, 51 (2.5%); previous adverse drug reaction to β-blockers, 24 (1.2%); current amiodarone use, 11 (0.5%); and others, 33 (1.6%); for a total of 1262. Of 762 eligible patients, 262 refused consent and 4

Discussion

As a population, patients undergoing vascular surgery are considered to have one of the highest risks.13, 14 Our results show that the RRR achieved with perioperative metoprolol in the vascular population is smaller than previously reported and is not significant. Our cardiac death and nonfatal MI rate in the placebo group was 8.8% and was comparable with other studies.14, 15, 16 The primary composite event rate of 12% in our control group, although lower than expected, was comparable with

References (23)

W.C. Krupski et al.
Comparison of cardiac morbidity rates between aortic and infrainguinal operations: two-year follow-up
J Vasc Surg
(1993)
G.J. L'Italien et al.
Comparative early and late cardiac morbidity among patients requiring different vascular surgery procedures
J Vasc Surg
(1995)
L. Goldman et al.
Multifactorial index of cardiac risk in noncardiac surgical procedures
N Engl J Med
(1977)
A.S. Detsky et al.
Predicting cardiac complications in patients undergoing non-cardiac surgery
J Gen Intern Med
(1986)
R.H. Bode et al.
Cardiac outcome after peripheral vascular surgery. Comparison of general and regional anesthesia
Anesthesiology
(1996)
D.T. Mangano et al.
Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group
N Engl J Med
(1996)
P.J. Devereaux et al.
Are the recommendations to use perioperative β-blocker therapy in patients undergoing noncardiac surgery based on reliable evidence?
Can Med Assoc J
(2004)
D. Poldermans et al.
The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group
N Engl J Med
(1999)
P.A. Grayburn et al.
Cardiac events in patients undergoing noncardiac surgery: shifting the paradigm from noninvasive risk stratification to therapy
Ann Intern Med
(2003)
J.S. Alpert et al.
Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction
J Am Coll Cardiol
(2000)

J.F. Baron et al.

Dipyridamole-thallium scintigraphy and gated radionuclide angiography to assess cardiac risk before abdominal aortic surgery

N Engl J Med

(1994)

Cited by (326)

Editor's Choice – European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Abdominal Aorto-Iliac Artery Aneurysms
2024, European Journal of Vascular and Endovascular Surgery
The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy.
The guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to a modified European Society of Cardiology grading system, where the strength (class) of each recommendation is graded from I to III and the letters A to C mark the level of evidence.
A total of 160 recommendations have been issued on the following topics: Service standards, including surgical volume and training; Epidemiology, diagnosis, and screening; Management of patients with small abdominal aortic aneurysm (AAA), including surveillance, cardiovascular risk reduction, and indication for repair; Elective AAA repair, including operative risk assessment, open and endovascular repair, and early complications; Ruptured and symptomatic AAA, including peri-operative management, such as permissive hypotension and use of aortic occlusion balloon, open and endovascular repair, and early complications, such as abdominal compartment syndrome and colonic ischaemia; Long term outcome and follow up after AAA repair, including graft infection, endoleaks and follow up routines; Management of complex AAA, including open and endovascular repair; Management of iliac artery aneurysm, including indication for repair and open and endovascular repair; and Miscellaneous aortic problems, including mycotic, inflammatory, and saccular aortic aneurysm. In addition, Shared decision making is being addressed, with supporting information for patients, and Unresolved issues are discussed.
The ESVS Clinical Practice Guidelines provide the most comprehensive, up to date, and unbiased advice to clinicians and patients on the management of abdominal aorto-iliac artery aneurysms.
Intraoperative hypotension in noncardiac surgery patients with chronic beta-blocker therapy: A matched cohort analysis
2023, Journal of Clinical Anesthesia
To explore the incidence of intraoperative hypotension in patients with chronic beta-blocker therapy, expressed as time spent, area and time-weighted average under predefined mean arterial pressure thresholds.
Retrospective analysis of a prospective observational cohort registry.
Patients ≥60 years undergoing intermediate- to high-risk noncardiac surgery with routine postoperative troponin measurements on the first three days after surgery.
1468 matched sets of patients (1:1 ratio with replacement) with and without chronic beta-blocker treatment.
None.
The primary outcome was the exposure to intraoperative hypotension in beta-blocker users vs. non-users. Time spent, area and time-weighted average under predefined mean arterial pressure thresholds (55–75 mmHg) were calculated to express the duration and severity of exposure. Secondary outcomes included incidence of postoperative myocardial injury and thirty-day mortality, myocardial infarction (MI) and stroke. Furthermore, analyses for patient subgroup and beta-blocker subtype were conducted.
In patients with chronic beta-blocker therapy, no increased exposure to intraoperative hypotension was observed for all characteristics and thresholds calculated (all P > .05). Beta-blocker users had lower heart rate before, during and after surgery (70 vs. 74, 61 vs. 65 and 68 vs. 74 bpm, all P < .001, respectively). Postoperative myocardial injury (13.6% vs. 11.6%, P = .269) and thirty-day mortality (2.5% vs. 1.4%, P = .055), MI (1.4% vs. 1.5%, P = .944) and stroke (1.0% vs 0.7%, P = .474) rates were comparable. The results were consistent in subtype and subgroup analyses.
In this matched cohort analysis, chronic beta-blocker therapy was not associated with increased exposure to intraoperative hypotension in patients undergoing intermediate- to high-risk noncardiac surgery. Furthermore, differences in patient subgroups and postoperative adverse cardiovascular events as a function of treatment regimen could not be demonstrated.
The Effect of Intravenous and Oral Beta-Blocker Use in Patients with Type B Thoracic Aortic Dissection
2022, Annals of Vascular Surgery
Beta-blockers have become the cornerstone for medical management in patients with chronic type B aortic dissection (TBAD). However, the effect of being on and/or receiving intravenous beta-blockers during hospitalization on outcomes of surgical repair of TBAD is not fully described. We sought to investigate this association during open surgical repair (OSR) and endovascular (Endo) intervention for nontraumatic TBAD.
The Premier Healthcare Database was inquired (June/2009–March/2015). Patients with nontraumatic isolated TBAD were identified via ICD-9-CM diagnosis and procedural codes. Patients with codes that indicated TAAD were excluded. In-hospital mortality, cardiac complications (CHF, MI, arrythmia) and stroke were evaluated. Log binomial regression analyses with bootstrapping were performed to assess the relative risk of adverse outcomes.
A total of 1,752 were admitted for OSR (54.3%) and Endo (45.7%) TBAD repair. Use of oral beta blocker (BB) was 16.0% in OSR and 56.4% in Endo groups. In each arm, patients on BB were more likely to be diabetic, on aspirin or statin and more likely to receive additional IV BB than nonBB patients. There was no significant difference in age, sex, race, or prior history of CHF between BB and nonBB groups. Mortality was proportionally lower in patients on BB in OSR group (7.9% vs. 16.7%; P = 0.006) and Endo (3.3% vs. 9.2%; P < 0.001). The adjusted relative risk for mortality and stroke were significantly lower in oral BB recipients compared with none [aRR (95% CI): 0.53 (0.32–0.90) and 0.46 (0.25–0.87); both P ≤ 0.02]. IV metoprolol was the only IV BB that reduced mortality [aRR (95% CI): 0.62 (0.46–0.85); P = 0.003]. A dose of ≤10 mg was associated with significant mortality reduction: 6.3% (3.0–9.5%) compared with 8.1% (4.6–11.6%) in no IV BB group. Cardiac complications were not affected by BB use.
For patients with nontraumatic TBAD, use of oral BB was associated with significant protection against in-hospital mortality and stroke following repair. Metoprolol was the only Intravenous BB type associated with improved survival. Further research is warranted to elucidate the effect of beta-blockers on the long-term surgical outcomes of TBAD.
How Should Beta-Blockers Be Used Perioperatively?
2022, Evidence-Based Practice of Anesthesiology
Perioperative beta-blockade (PBB) has been advocated for the reduction of cardiac risk for noncardiac surgery, primarily through prevention of major adverse cardiac events (MACE). Nevertheless, the data and recommendations supporting PBB have been both changing and conflicting. Early interest in using beta-blockers to protect against perioperative cardiovascular complications was supported by a small number of randomized controlled trials (RCTs) and reviews, and beta-blockers were quickly adopted because their perceived benefit was considered large with few documented adverse effects. More recent data however, suggest that PBB may carry significantly increased risk for perioperative morbidity and mortality for many patients, particularly through increased risk for stroke and hypotension. This chapter aims to provide a review of the development of literature surrounding PBB, discuss the uncertainties surrounding PBB, and review the American and European guidelines surrounding use of beta-blockers during the perioperative period. A focus of this chapter is on recent updates in the literature and recommendations over the past decade.
Generalisability of randomised trials evaluating perioperative β-blocker therapy in noncardiac surgery
2020, British Journal of Anaesthesia
The limited applicability of evidence from RCTs in real-word practice is considered a potential bottleneck for evidence-based practice but rarely systematically assessed. Using our failure to recruit patients into a perioperative beta-blocker trial, we set out to analyse the restrictiveness and generalisability of trial eligibility criteria in a real-world cohort.
We prospectively included adult patients (≥18 yr) scheduled for elective noncardiac surgery at an academic tertiary care facility who were screened for inclusion in a planned perioperative beta-blocker RCT, which was terminated owing to recruitment failure. The primary outcome was the proportion of screened patients who matched the eligibility criteria of 36 published RCTs included in a large Cochrane meta-analysis on perioperative beta-blocker therapy. The pragmatic/explanatory level of each RCT was assessed using the PRagmatic–Explanatory Continuum Indicator Summary 2 (PRECIS-2) score, which ranges from 9 points (indicating a very explanatory study) to 45 points (indicating a very pragmatic study).
A total of 2241 patients (54% female, n=1215; 52 [standard deviation, 20] yr) were included for the assessment of trial eligibility between October 2015 and January 2016. Only a small proportion of patients matched the inclusion and exclusion criteria for each of the 36 RCTs, ranging from 53% to 0%. The average proportion of patients who did match the eligibility criteria of all 36 RCTs was 6.5% (n=145; 95% confidence interval, 6.3–6.6). A higher PRECIS-2 score was associated with a higher proportion of matching patients (P<0.001).
Trial eligibility criteria in perioperative beta-blocker therapy trials are overly restrictive and not generalisable to a real-world surgical population.
EudraCT#: 2015-002366-23.
Perioperative beta-blockers: Friends or foes?
2020, Praticien en Anesthesie Reanimation
La fréquence cardiaque est un déterminant important du débit cardiaque et la compétence chronotropique un élément essentiel de l’adaptation au stress chirurgical et aux dyshoméostasies périopératoires. À la fois adaptative et potentiellement délétère, notamment chez le patient à risque cardiaque, la tachycardie sinusale pose un problème diagnostique et son contrôle ciblé par des médicaments chronotropes négatifs est une arme à double tranchant. Les bêtabloquants représentent une classe thérapeutique particulièrement intéressante pour le maintien périopératoire de la balance énergétique du myocarde. Ils ont un impact pronostique favorable largement démontré dans la littérature. Ils peuvent néanmoins entraîner des effets indésirables graves. Leur utilisation et leur maintien avant comme après la chirurgie doivent reposer sur une stricte analyse bénéfices/risques individuels. Chez le patient à haut risque cardiovasculaire, le traitement doit être maintenu jusqu’au jour de la chirurgie et repris le plus tôt possible après l’intervention. Cela nécessite une surveillance accrue du patient, idéalement dans une unité de soins critiques. Les nouveaux bêtabloquants injectables à demi-vie courte sont bien adaptés au contexte et aux objectifs périopératoires.
Heart rate is a major determinant of cardiac output and the chronotropic competence is of paramount importance for surgical stress adaptation. Simultaneously adaptive and deleterious, especially in cardiac risk patients, perioperative tachycardia asks several diagnostic difficulties and targeted heart rate control by means of negative chronotropic drugs is a double-edged sword. Beta-blockers are a therapeutic class of great interest to maintain perioperative myocardial oxygen balance. They have been proving benefits on cardiac outcomes in high-risk patients for a long time. However, they also provide potential serious side effects. Therefore, their use and early resumption before and after surgery must be considered on a strict individual risk/benefit analysis. Beta-blockers should be maintained up to the morning of surgery and resume as soon as possible postoperatively. Finally, the new intravenous beta-blockers with a short half-life are safe and well adapted to perioperative objectives.

View all citing articles on Scopus

: The study was funded by the Heart and Stroke Foundation of Canada (grant no. NA3779).

View full text

Clinical InvestigationPeripheral Vascular DiseaseThe effects of perioperative β-blockade: Results of the Metoprolol after Vascular Surgery (MaVS) study, a randomized controlled trial

Background

Methods

Results

Conclusion

Section snippets

Study population

Results

Discussion

J Vasc Surg

J Vasc Surg

Multifactorial index of cardiac risk in noncardiac surgical procedures

N Engl J Med

Predicting cardiac complications in patients undergoing non-cardiac surgery

J Gen Intern Med

Cardiac outcome after peripheral vascular surgery. Comparison of general and regional anesthesia

Anesthesiology

Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group

N Engl J Med

Are the recommendations to use perioperative β-blocker therapy in patients undergoing noncardiac surgery based on reliable evidence?

Can Med Assoc J

The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group

N Engl J Med

Cardiac events in patients undergoing noncardiac surgery: shifting the paradigm from noninvasive risk stratification to therapy

Ann Intern Med

Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction

J Am Coll Cardiol

Dipyridamole-thallium scintigraphy and gated radionuclide angiography to assess cardiac risk before abdominal aortic surgery

N Engl J Med

Clinical Investigation
Peripheral Vascular Disease
The effects of perioperative β-blockade: Results of the Metoprolol after Vascular Surgery (MaVS) study, a randomized controlled trial