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Overview
PAD (peripheral arterial disease) a marker for MI and IS Epidemiological data on PAD
Risk factors Prevalence Atherothrombosis coexistence of PAD, coronary and cerebrovascular disease Natural history Low ABPI as an independent predictor of ischaemic risk
Symptomatology of PAD Diagnosis and management of PAD Clopidogrel a new standard of treatment for atherothrombosis
PAD
Hypertension
Diabetes Hyperlipidaemia Fibrinogen
Atherosclerosis
Atherothrombosis
Homocysteinaemia
Ischaemic stroke
Myocardial infarction
Murabito JM et al. Circulation 1997;96:4449; Laurila A et al. Arterioscler Throm Vasc Biol 1997;17:29102913; Malinow MR et al. Circulation 1989;79:11801188; Brigden ML. Postgrad Med 1997;101:249262.
17 Western European countries. Statistical Supplement; WHO Yearbooks, Annual Statistics, 1997; Criqui MH et al. Vasc Med 1997;2:221226; 3Shinozaki T et al. J Clin Epidemiol 1998;15:12631269; 4Kornitzer M et al. Angiology 1995;46:211219. *ABPI < 0.9, symptomatic or not, diagnosed or not.
2
increase with age Prevalence in men aged 4550 years is 1% Prevalence is 33.5% in men aged > 50 years Similar trend in women, increase with age
More common in men than in women
Twice as many men as women aged > 50 years have intermittent
Men
20
10 0
Yes
No
PAD
Yes
No
Atherothrombosis symptomatic atherosclerosis in CAPRIE (overlap between PAD, CAD and CVD)
CAPRIE1 (n = 19 185)
Cerebrovascular disease (CVD) Coronary artery disease (CAD)
24.6% 3.8%
7.3% 3.3%
29.9%
11.9%
19.2%
Peripheral Arterial Disease (PAD)
1CAPRIE
Cerebrovascular outcome
5.2
Clopidogrel Aspirin
Local Events
Worsening claudication 25 patients Surgical revascularization 10 patients Major amputation 2 patients
Dormandy JA. Hosp Update 1991;April:314318.
Systemic Events
10 to 20 non-fatal MIs or strokes
PLUS
30 deaths: CHD 15 Other cardiovascular and cerebrovascular 5 Non-cardiovascular 10
PAD mortality 10-year survival rates of subjects in the San Diego Artery Study
1.00
Normal 0.75
Survival
Asymptomatic
Symptomatic
Severe symptomatic
6 8 Time (years)
10
12
86
15
Breast cancer1
18
Hodgkin's disease1
28
38
PAD2
1American
Cancer Society. Cancer Facts and Figures 1997. RF, Bernhard VM. In: Vascular Surgery (Rutherford RB, ed). Philadelphia, PA: WB Saunders: 1989;chap 53.
2Kampozinski
individuals with intermittent claudication were twice as high as those in healthy controls (17 years follow-up study)
Increased mortality even after adjustment for coronary
risk factors Cardiac ischaemia at baseline Systolic blood pressure Plasma cholesterol concentration Smoking behaviour Employment grade Degree of glucose intolerance
Smith GD et al. Circulation 1990;82:19251931.
ABPI
ABPI measurement is underutilized and can be usefully
invasive
Kornitzer M et al. Angiology 1995;46:211219. McKenna M et al. Atherosclerosis 1991;87:119128. Dormandy JA et al. J Cardiovasc Surg 1989;30:5057.
ABPI inverse relationship with 5-year risk of cardiovascular events and death
2.5 Risk relative to ABPI 10.2% relative risk increase per 0.1 decrease in ABPI (p = 0.041)
2.0
1.5
0.6
0.8
1.0
Symptomatology of PAD
Intermittent claudication
Exercise-induced ischaemic calf-muscle pain while walking and/or weakness, relieved by rest
Mortality rate from stroke and MI two to three times greater than in age-matched controls1
Prognosis varies with multiple risk factors and/or severity of disease
Critical limb ischaemia Pain at rest, eventually resulting in gangrene and amputation2
1Dormandy
JA et al. J Cardiovasc Surg 1989;30:5057. 2European Working Group on Critical Leg Ischemia. Circulation 1991;84(Suppl IV):IV1IV26.
Diagnosis of PAD
Evaluation of pulses and auscultation of bruits Ankle:arm blood pressure index (ABPI)
Ratio of ankle:brachial systolic blood pressure Simple, non-invasive, suitable for routine screening
Exercise testing
Pain-free and maximal walking distance Size and duration of drop in ankle systolic BP upon
claudication
Pharmacological treatment
Antiplatelet therapy Control risk factors (e.g. hypertension, blood glucose) Vasodilators for symptomatic relief?
Endovascular
Surgical
Endarterectomy
established PAD
Clopidogrel 75 mg od versus aspirin 325 mg od Follow-up of 13 years (mean 1.91 years) Combined primary endpoint of IS, MI or vascular
death
CAPRIE Steering Committee. Lancet 1996;348:13291339.
120
80
19
24
40
30
33
36
1CAPRIE
Steering Committee. Lancet 1996;348:13291339. Trialists' Collaboration. BMJ 1994;308:81106. 3Fisher LD. J Am Coll Cardiol 1998;31(Suppl A):49A.
2Antiplatelet
Based on the APTC findings,2 in a population similar to CAPRIE, for each 1000 patients treated per year, aspirin can be expected to prevent 19 events and clopidogrel, 24.1
104
Clopidogrel Aspirin
71
P < 0.05
P < 0.01
255
191 37
51
GI haemorrhages
GI ulcer
* The proportions of patients with diarrhoea, rash or pruritus were higher in the clopidogrel group than in the aspirin group
1CAPRIE 3Lok
Steering Committee. Lancet 1996;348:13291339; 2Bogousslavsky J. Cerebrovasc Dis 1998;8(Suppl 4):43; DJA. Eur Heart J 1998;19(Abstract Suppl):52.
Summary 1
PAD is a marker of atherosclerosis in the coronary
ABPI is a non-invasive, easily performed measurement that reliably predicts ischaemic risk in PAD patients
Summary 2
for secondary prevention in atherothrombotic patients, including those with diagnosed PAD
Reduces the risk of all major events