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Intervention Review

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Pharmacological treatment of vascular risk factors for reducing mortality and cardiovascular events in patients with abdominal aortic aneurysm

  1. Lindsay Robertson1,*,
  2. Edmond Atallah2,
  3. Gerard Stansby3

Editorial Group: Cochrane Vascular Group

Published Online: 21 JAN 2014

Assessed as up-to-date: 10 APR 2013

DOI: 10.1002/14651858.CD010447.pub2


How to Cite

Robertson L, Atallah E, Stansby G. Pharmacological treatment of vascular risk factors for reducing mortality and cardiovascular events in patients with abdominal aortic aneurysm. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD010447. DOI: 10.1002/14651858.CD010447.pub2.

Author Information

  1. 1

    Freeman Hospital, Department of Vascular Surgery, Newcastle upon Tyne, UK

  2. 2

    Mid Cheshire Hospitals NHS Foundation Trust, Leighton Hospital, Crewe, Cheshire, UK

  3. 3

    Freeman Hospital, Northern Vascular Centre, Newcastle upon Tyne, UK

*Lindsay Robertson, Department of Vascular Surgery, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, High Heaton, Newcastle upon Tyne, NE7 7DN, UK. lindsay.robertson@nuth.nhs.uk. lindsay.robertson@ed.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 21 JAN 2014

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This is not the most recent version of the article. View current version (12 JAN 2017)

 
Characteristics of included studies [ordered by study ID]
Yang 2006

MethodsStudy type: Double-blind randomised controlled trial

Study aim: To test the hypothesis that, at 30 days and 6 months after vascular surgery, the perioperative administration of metoprolol reduces the incidence of cardiac complications defined as cardiac death, nonfatal MI, CHF, unstable angina, and dysrhythmias requiring treatment.

Country: Canada

Setting: 3 tertiary care centres: General Campus, Hamilton Health Sciences; Victoria Campus, London Health Sciences; and Kingston General Hospital between 1999 and 2002.

Recruitment: all patients undergoing vascular surgery were screened for eligibility. Elective vascular surgical patients are evaluated by internists, cardiologists, or anaesthesiologists in preoperative clinics. Screening was also undertaken on the wards when applicable


ParticipantsInclusion criteria: Patients with American Society of Anesthesiology class 3 or less and undergoing abdominal aortic surgery and infrainguinal or axillofemoral revascularisation

Exclusion criteria: current or recent β-blocker use, current amiodarone use, airflow obstruction requiring treatment, history of CHF, history of atrioventricular block, previous adverse drug reactions to β-blockers, and previous participation in the MaVS study

Gender: Placebo group 184 M/66 F; Metoprolol group 193 M/53 F

Age: Placebo patients mean 65.9 ± 10.0 years; Metoprolol patients mean 66.4± 10.0 years

Co-morbidities:

Prior MI: 30 placebo, 37 metoprolol

Angina: 25 placebo, 18 metoprolol

Diabetes mellitus (DM) on treatment: 37 placebo, 54 metoprolol

Permanent pacemaker: 1 placebo, 0 metoprolol

AAA subgroup: 116 placebo, 111 metoprolol


InterventionsTreatment: Metoprolol administered orally or intravenously. Patients weighing ≥ 75 kg received metoprolol 100 mg; patients weighing between 40 and 75 kg received metoprolol 50 mg; and patients weighing ≤ 40 kg received metoprolol 25 mg OR intravenously at 1 mg/mL for 15 minutes. IV treatment was converted to oral as soon as oral intake was tolerated

Control: Placebo administered orally as tablet or given intravenously as saline 0.2 mL/kg (to a maximum of 15 mL), diluted with 20 mL of saline for 15 minutes

Duration: Metoprolol or placebo given orally 2 hours preoperatively. Within 2 hours of surgery, metoprolol or placebo were give intravenously or orally. IV drug administered over 15 minutes every 6 hours. Oral administration was twice daily. Treatment lasted for 5 days or until hospital discharge, whichever occurred sooner

Co-interventions: Short-acting vasoactive medications including phenylephrine, ephedrine, nitroglycerine, and low-dose dopamine were allowed. Open-label β-blocker use was strongly discouraged except when deemed absolutely necessary by the attending physician. Circumstances for open-label use were generally for rapid heart rate control. Intraoperatively, esmolol, if deemed absolutely necessary, was allowed


OutcomesPrimary outcome: Composite of cardiac complications at 30 days post operation including; cardiac death1, nonfatal MI2, CHF3, unstable angina4, and dysrhythmia requiring treatment defined as atrial fibrillation or ventricular dysrhythmias5

1 Cardiac death was defined as either the ultimate cause of death traceable to an initiating cardiac complication or death in which the cause was not clearly identifiable or was insufficient to account for the demise in a patient who was not expected to succumb at the time of death.

2 Nonfatal MI within 3 postoperative deaths diagnosed if ≥ 1 of the following present: chemical evidence of MI or new Q waves > 0.04 s on 2 contiguous leads. Beyond 3 days, nonfatal MI was determined by attending physicians with supporting documentation of hospital chart, troponins, and pre- and postoperative electrocardiograms.

3 Unstable angina diagnosed by attending physician when anginal symptoms necessitated a change in medications, coronary revascularisation, or intensive care admission.

4 Congestive heart failure was diagnosed clinically with the requisite radiographic evidence.

5 Dysrhythmia requiring treatment was defined as one of the following: ventricular fibrillation requiring counter shock, ventricular tachycardia requiring counter shock or medication, or atrial fibrillation > 15 minutes in duration requiring counter shock or medication.

Secondary outcomes:

1. Study drug discontinuation due to bronchospasm, advanced heart blocks, hypotension (systolic BP < 90 mmHg) or bradycardia (50 beats/min)

2. Reoperation or amputation

3. Intraoperative hypotension and bradycardia requiring treatment by the attending anaesthesiologists


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization was constructed in blocks of 4 by the study statistician"

Allocation concealment (selection bias)Unclear riskComment: Methods of concealment of allocation are not stated. Insufficient information to permit judgement of low or high risk of selection bias

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The patients, investigators, and all caretakers were blinded to the study randomisation. Blinding of randomisation was maintained throughout clinical decisions on reducing or discontinuing the study medication"

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "All data were collected by the participating centres and evaluated by the adjudication committee in a blinded fashion"

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Completion of the study protocol was similar in the placebo (77.6%) and treatment groups (75.2%). Discontinuation of the study protocol was also similar in the placebo and treatment groups; primary outcome event (30 and 25,respectively); patient/family/physician preference (27 and 14, respectively); open-label β-blockers (24 and 14, respectively); patient death (3 and 0, respectively), atrioventricular block (2 and 3, respectively), bronchospasm (1 and 4, respectively); and other reason (11 and 13, respectively)." 

Comment: All missing data accounted for and similarly balanced across the two treatment groups. Low risk of attrition bias

Selective reporting (reporting bias)Low riskQuote: "Our results show that the RRR achieved with perioperative metoprolol in the vascular population is smaller than previously reported and is not significant" 

Comment: Authors commented on study results in relation to expected outcomes from other published reports. Furthermore, all of the primary and secondary pre-specified outcomes were reported.

Other biasLow riskThe study appears to be free from other sources of bias

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Cesanek 2008Study examined beta-blocker related complications in patients undergoing vascular surgery. Authors were contacted for outcome data for AAA participants but did not respond to communication

DECREASE StudyThe principal investigator of the DECREASE Study was dismissed for misconduct including failing to obtain patient written informed consent and negligent data collection. A full copy of the report issued by the Erasmum Medical Centre can be found here:

http://www.erasmusmc.nl/5663/135857/3675250/3706798/Integrity_report_2012-10.pdf?lang=en

Durazzo 2004A subgroup of 56 participants underwent a AAA repair but specific outcome data for these patients was not presented. Through personal communication, the study author confirmed that these data were not available

Kouvelos 2013Of the 262 participants studied, 66% were taking antiplatelets, 19% anticoagulants, 23% calcium antagonists, 33% ACE inhibitors and 15% were taking angiotensin II receptors prior to randomisation. Outcomes in this study could not be attributed to one specific drug and therefore this study was excluded from this review

Mackey 2006Prospective study which measured the incidence of perioperative myocardial ischaemic injury in high risk vascular surgery patients. Not a randomised controlled trial and no drugs administered

Mangano 1996The study did not report if there was a subgroup of participants with AAA. Attempts were made to contact the author to see if this data was available but contact could not be made

Neilipovitz 2012Patients in this study were taking co-medications (angiotensin drugs, calcium channel blockers, beta blockers, acetylsalicylic acid, clopidogrel) that we planned to assess in this review. Outcomes in this study could not be attributed to one specific drug and therefore this study was excluded from the review

POBBLE TrialOf the 103 participants included in this study, 38% underwent aortic repair. However outcome data for this subgroup was not presented. Attempts were made to retrieve this data but the study authors did not respond to communication

POISE StudyPersonal communication with the author of the study confirmed that data for the AAA participants were not available

 
Comparison 1. Metoprolol versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 All-cause mortality, 30 days1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Cardiovascular death, 30 days1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 AAA-related death, 30 days1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Nonfatal cardiovascular event, 30 days1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 All-cause mortality, 6 months1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Cardiovascular death, 6 months1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 7 Nonfatal cardiovascular event, 6 months1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected