CARDIOVASCULAR DISEASES

Health Evidence Bulletins - Wales (logo)
Team Leader: Dr David Fone

Date of completion: 30.9.98

8: Aortic aneurysm and peripheral vascular disease

This bulletin is a supplement to, not a substitute for, professional skills and experience. Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation.

The Statements The Evidence
8.1 Abdominal aortic aneurysm
8.1a. Abdominal aortic aneurysm is present in about 5% of men and 2% of women aged over 65, and is usually asymptomatic unless rupture occurs, in around 6 per 1000 men aged over 65. The five year all-cause mortality is between 10% to 15%; in men over 65 ruptured aortic aneurysm accounts for 1% of all deathsi. The published evidence suggests that beyond abdominal palpation in those over 60 years oldii, screening for abdominal aortic aneurysms is not a proven effective use of resourcesi-iii.
(Health gain notation – 4 "unknown")

Caveat: Screening in men aged 65 to 80 was associated with a significant reduction in deaths from ruptured aortic aneurysmi. All-cause mortality was not reduced as the incidence of ruptured aneurysm is lowi-iii. A much larger multi-centre trial is necessary.

i. Scott RAP, Wilson NM, Ashton HA, Ray DN. Influence of screening of the incidence of ruptured abdominal aortic aneurysm: 5 year results of a randomised controlled study. British Journal of Surgery 1995:82:1066-70
(Type II evidence – randomised controlled trial of 15,775 men and women aged 65 to 80 years randomised to ultrasound screening or control with five year follow-up)
ii. Frame PS, Fryback DG, Patterson C. Screening for abdominal aortic aneurysm in men aged 60 to 80 years. A cost effective study. Annals of Internal Medicine 1993;119:411-16
(Type IV evidence – computer modelling cost-effectiveness study comparing physical examination with ultrasound in men aged 60 to 80 years)
iii. Abdominal Aortic Aneurysm. Bandolier 1996, Number 27. Volume 3 Issue 5
http://www.jr2.ox.ac.uk/bandolier/band27/b27-3.html
(Type II evidence – review of randomised controlled trial, reference i)
8.1b. A Cochrane Review of whether beta-blockade reduces the rate of aortic dilatation in abdominal aortic aneurysm is due for publication in 1999i.
(Health gain notation – 4 "unknown")
i. Powell JT, Quick C. Does beta-adrenergic blockade limit the rate of dilatation of the diseased aorta? Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review)
8.1c. A Cochrane Review to assess whether there are significant differences in outcomes between different materials used as aortic grafts is due for publication in 1999i.
(Health gain notation – 4 "unknown")
i. Faris I, Quigley F. Graft materials used for abdominal aortic repair. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review)

Top

8.2 Peripheral vascular disease
8.2a. Peripheral vascular disease results from atheromatous narrowing of the arteries to the legs. Symptoms may range from calf pain on exercise "intermittent claudication", to rest pain and gangrene. Intermittent claudication is the commonest symptom occuring in around up to 5% of men and 2.5% of women aged 60 or over. The five year mortality for men ranges from 5% to 17%, with coronary heart disease, stroke and ruptured aortic aneurysm as the leading causes of deathI,ii. Evidence-based guidelines for the diagnosis, medical and surgical treatmentI and angioplastyii in the management of patients with peripheral vascular disease are available.
(Health gain notation – 1 "beneficial")
i. Weitz JI, Byrne J, Clagett GP, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. American Heart Association. Circulation 1996;94:3026-49
http://www.americanheart.org/Scientific/statements/
1996/1201.html

(Type V evidence – expert opinion)
ii. Pentecost MJ, Criqui MH, Dorros G, et al. Guidelines for peripheral percutaneous transluminal angioplasty of the abdominal aorta and lower extremity vessels: a statement for health professionals from a special writing group of the councils on cardiovascular radiology, arteriosclerosis, cardio-thoracic and vascular surgery, clinical cardiology and epidemiology and prevention, the American Heart Association. Circulation 1994;89:511-31
http://www.americanheart.org/Scientific/statements/
1994/019401.html

(Type V evidence – expert opinion)
8.3 Medical management
8.3a. Smoking cessation improves the symptoms of intermittent claudication, and reduces the complications of peripheral vascular diseasei.
(Health gain notation – 1 "beneficial")
i. Radack K, Wyderski RJ. Conservative management of intermittent claudication. Annals of Internal Medicine 1990;113:135-46
(Type IV evidence – review of observational studies of smoking cessation)
8.3b. The use of lipid-lowering therapy in peripheral vascular disease is of unproven benefit. The evidence suggests a trend towards reduced total mortality, lower total cholesterol and progression of underlying atheromai.
(Health gain notation – 4 "unknown")
Caveat: Results should be interpreted with caution due to the variation in types of trials and small numbers of events. Future trials of lipid lowering therapy with statins should include peripheral vascular disease outcomes.
i. Leng GC, Price JF, Jepson RG.Lipid-lowering therapy in the treatment of lower limb atherosclerosis. Cochrane Review [Updated 14 August 1998]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 700 patients in seven trials of diet and non-statin drug therapy)

Top

8.3c. Exercise for patients with intermittent claudication improves maximal walking distance compared to control (pooled results from three trials odds ratio 6.51; 95% CI: 4.36, 8.66) with an overall improvement in walking ability of 150% (range 74% to 230%). Drug therapy with pentoxifylline may be of greater benefit in selected patients. Surgery may be more effective than exercise in the short-term but is associated with increased mortality and morbidityi.
(Health gain notation – 1 "beneficial")
Caveat: A large trial with long-term follow-up is required to compare the effectiveness of different supervised and unsupervised exercise regimes and to compare exercise with pentoxifylline. Cost-benefit analyses are required.
i. Leng GC, Fowler B, Ernst E. Exercise for intermittent claudication. Cochrane Review [Updated 9 April 1998]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 200 patients with intermittent claudication in nine trials of exercise vs. control or vs. medical or surgical therapy)
8.3d. Cellular mechanisms of action suggest pentoxifylline may be an effective treatment in patients with peripheral vascular disease. A Cochrane Review is due for publication in 1999i.
(Health gain notation – 4 "unknown")
i. Juni P, Fux C, Hertog MGL, Ernst E. Pentoxifylline for the treatment of intermittent claudication. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis)
8.3e. Iloprost may be effective in ulcer healing or relief of pain (rate difference 0.22, 95% CI: 0.12, 0.33) and in preventing amputation (rate difference –0.12, 95% CI: -0.21, -0.03) in patients with severe occlusive peripheral vascular disease, in whom surgery had failed or is impracticali.
(Health gain notation – 4 "unknown")
Caveat: Criteria for assessment of validity of primary studies not stated. Further assessment of cost-effectiveness is necessary in large randomised controlled trials.
i. Loosemore TM, Chalmers TC, Dormandy JA. A meta-analysis of randomised placebo control trials in fontaine stage III and stage IV peripheral occlusive arterial disease. International Angiology 1994;13:133-42. In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 705 patients with severe peripheral vascular disease in six trials of iloprost vs. placebo)
8.3f. A Cochrane Review of the effectiveness of haemodilution as a treatment for peripheral vascular disease is due for publication in 1999i.
(Health gain notation – 4 "unknown")
i. Ernst E, Thompson J, Resch KL. Haemodilution for peripheral vascular disease. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 2. Oxford: Update Software, 1998
(Type I evidence – systematic review)

Top

8.3g. A Cochrane Review to determine the efficacy of antiplatelet agents: aspirin, dipyridamole, indobufen, picotamide, suloctidil, sulphinpyrazone and ticlopidine on improving pain-free and total walking distance in patients with moderate intermittent claudication is due for publication in 19991.
(Health gain notation – 4 "unknown")
i. Saenz A, Ausejo M, Hood S, Barber G, Pham B, Moher D. Antiplatelet agents for intermittent claudication: aspirin, dipyridamole, indobufen, picotamide, suloctidil, sulphinpyrazone and ticlopidine. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis)
8.3h. Evidence-based guidelines for drug therapy in peripheral vascular disease are availablei.
(Health gain notation – 1 "beneficial")
i. Scottish Intercollegiate Guidelines Network (SIGN). Drug therapy for peripheral vascular disease. Edinburgh: Royal College of Physicians, 1998
http://www.show.scot.nhs.uk/sign/html/html27.htm
(Type V evidence – expert opinion)
8.4 Surgical management
8.4a. Three Cochrane Reviews to assess the comparative effectiveness of surgery and thrombolysis for acute limb ischaemiai, different fibrinolytic agentsii, and optimal infusion techniquesiii, are due for publication in 1999.
(Health gain notation – 4 "unknown")
i. Berridge DC, Kessel D. Surgery vs. thrombolysis for acute limb ischaemia. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review)
ii. Berridge DC, Kessel D. Fibrinolytic agents for acute arterial occlusion. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review)
iii. Berridge DC, Kessel D. Optimal infusion technique in peripheral arterial thrombolysis. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review)
8.4b. A Cochrane Review to determine the most effective graft in femoro-popliteal bypass surgery is due for publication in 1999i.
(Health gain notation – 4 "unknown")
i. Mamode N, Scott RN. The best graft for femoro-popliteal bypass surgery. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review)

Top

8.4c. Two Cochrane Reviews to determine the efficacy of antiplatelet agentsi and anticoagulantsii in patients with lower limb atherosclerosis undergoing femoro-popliteal and femoro-distal bypass grafting are due for publication in 1999.
Health gain notation – 4 "unknown")
i. Adam DJ, Stonebridge PA. Antiplatelet therapy after peripheral arterial bypass surgery. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review)
ii. Adam DJ, Stonebridge PA. Anticoagulant therapy after peripheral arterial bypass surgery. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review)
8.4d. Angioplasty does not appear to be an effective treatment of mild or moderate intermittent claudication. In one trial, the angioplasty group were more likely to have a patent artery (odds ratio 5.5; 95% CI: 1.8, 17.0), but not a significantly better walking distance or quality of life. Ankle-brachial pressure indices were higher at six months in both trials, but in the second trial there were no significant differences in outcomes between the angioplasty and control groups at six year follow-upi.
(Health gain notation – 4 "unknown")
Caveat: Clinical heterogeneity and observer bias from lack of blinding require the results to be interpreted with caution. Further well-designed large scale trials are required to draw firm conclusions on the cost-effectiveness of angioplasty for mild to moderate claudication.
i. Fowkes FGR, Gillespie IN. Angioplasty (versus non-surgical management) for intermittent claudication. Cochrane Review [Updated 19 February 1998]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review of two small trials of angioplasty vs. exercise programme and usual care in patients with peripheral vascular disease not warranting reconstructive surgery)
8.5 Secondary prevention
8.5a. Antiplatelet therapy is associated with a 43% (SD 8%) reduction at mean follow-up of 19 months in the odds of reocclusion following peripheral arterial grafting or angioplasty in patients with peripheral vascular disease (benefit 92 (SD 15) per 1000 patients treated, p<0.000). Most patients received aspirin – where comparison between regimens and antiplatelet agents were possible no significant differences were notedi.
(Health gain notation – 1 "beneficial")
Caveat: The timing of commencement of therapy and duration of therapy should be investigated in further trials.
i. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy – II: Maintenance of vascular graft or arterial patency by antiplatelet therapy. British Medical Journal 1994;308:159-68.
http://www.bmj.com/cgi/content/full/308/6922/159
In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and sub-group meta-analysis of 3226 patients in 14 trials of antiplatelet therapy in patients with peripheral arterial disease)

Top

8.5b. Clopidogrel may be more effective than aspirin in the secondary prevention of non-fatal ischaemic stroke, non-fatal MI, or vascular death (the CAPRIE composite primary outcome) in patients with recent ischaemic stroke, MI, or symptomatic peripheral vascular disease: 5.32% vs. 5.83%; relative risk reduction 8.7%; 95% CI: 0.3, 16.5; p=0.043. No benefit was found for the secondary outcomes of vascular death alone or death from any cause. No major differences in safety were showni.
(Health gain notation – 2 "likely to be beneficial")
Caveat: Significant benefit of clopidogrel was only found for the protocol specified primary outcome. No benefit was shown for clopidogrel over aspirin in the four protocol specified secondary outcomes, including vascular and all-cause mortality. Sub-group analysis found significant heterogeneity between the three patient sub-groups, with significant benefit shown only in patients with previous history of peripheral vascular disease. Further trials and evidence of greater cost-effectiveness is required before the use of clopidogrel is justified over aspirin.
i. CAPRIE steering committee. A randomised, blinded trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-39
(Type II evidence – randomised controlled trial of 19,185 patients, mean 1.9 year follow-up)
8.5c. A Cochrane Review to determine the relative effectiveness and safety of ticlopidine and clopidogrel compared to aspirin in the secondary prevention of stroke and other important vascular outcomes in patients at high risk (previous TIA, ischaemic stroke, MI and peripheral vascular disease) is due for publication in 1999i.
(Health gain notation – 4 "unknown")
i. Hankey GJ, Dunbabin DW, Sudlow CLM. Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin in the secondary prevention of stroke and other important vascular events among high risk patients. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis)
Top

Contents Home

Health Evidence Bulletins: Wales, Duthie Library, UWCM, Cardiff CF14 4XN. e-mail: weightmanal@cardiff.ac.uk