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materi RTD PAD dr Bowo Pramono SpPD KEMD
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PLAVIX
Update Management of POADCurrent Meta-Analysis of Antiplatelet
R BOWO PRAMONO
PAPDI CABANG YOGYAKARTA
ATHEROTHROMBOTIC
Atherosclerotic Plaque
Rupture Plaque
Thrombus in to atheroma
Thrombus Formation
CHRONIC ISCHEMIA
Stable plaque
ACUTE EVENT
Occlusion
Emboli
Apa itu Peripheral Arterial Disease?
Arteri pada bagian extremities terjadi stenosis atau tersumbat karena atherosclerosis
Biasanya arteri yang besar atau sedang
Umunya didaerah percabangan
Lifestyle / Gaya Hidup
• Perokok +++Resiko utama atherosclerosis pada kaki dan coronary arteries
• Diet yang tidak tepat (fats)
• lifestyle
• Stress?
Siapa yang terkena resiko PAD?
Faktor yang tidak bisa dirubah
• Usia +++
• Laki laki ++
• Faktor Genetik
Siapa yang terkena resiko PAD?
Diagnosa PAD Evaluasi pulses dan suara bruits Ankle:arm blood pressure index (ABPI)
Ratio pd ankle:tekanan darah systole brachial Simple, non-invasive, baik utk screening scr rutin
Exercise testing Bebas rasa nyeri dan maximal waktu berjalan Ukuran dan waktu penurunan tekanan darah
systolic pd angkle saat terasa nyeri/ claudication
Weitz JI Weitz JI et alet al. . CirculationCirculation 1996;94:3026–3049. 1996;94:3026–3049.
The Ankle-Brachial Index
Lower extremity systolic pressure
Brachial artery systolic pressureABI =
Normal ABIICCLI
0.9 - 1.3<0.90<0.50
Doppler Ultrasound
• Mendeteksi claudication/nyeri.
• Objective mematikan lamanya waktu berjalan
• Monitoring waktu lamanya berjalan dengan standard yang ditetapkan
Kecepatan: 3 km/jam Slope: 10%
Treadmill Test
The treadmill test enables precise demonstration
of claudication
Fontaine Classification
Stage I
Stage II
Stage III
Stage IV
Asymptomatic:atherosclerosis developing
Stable claudications, pain on exercise, skindiscoloration
Rest pain
Trophic changes: ulcers, necrosis and gangrene
ABI and FONTAINE STAGEABI Clinical Manifestation> 1 Normal
0.9 - < 1 Asymptomatic> 0.5 – 0.9 IC mild - moderate
< 0.5 Rest pain
FONTAINE Clinical Manifestation Walking distanceI Asymptomatic
IIa IC mild 1-2 KM 200 MIIb IC moderate - severe < 200 MIII Rest painIV Ulcers / Gangrene
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
11Dormandy JA Dormandy JA et alet al. . J Cardiovasc SurgJ Cardiovasc Surg 1989;30:50–57. 1989;30:50–57.22European Working Group on Critical Leg Ischemia. European Working Group on Critical Leg Ischemia. CirculationCirculation 1991;84(Suppl IV):IV1–IV26. 1991;84(Suppl IV):IV1–IV26.
Stage II: Intermittent Claudication
Intermittent claudication – an independent risk factor for increased mortality rates
Smith GD et al. Circulation 1990;82:1925–1931.
In the Whitehall study (n = 18 388), mortality rates in 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 ischemia at baseline Systolic blood pressure Plasma cholesterol concentration Smoking behavior Employment grade Degree of glucose intolerance
Low ABPI is a strong predictor of cardiovascular mortality
Reduced ABPI is a significant independent predictor of cardiovascular and coronary mortality
Age-adjusted relative risks for 10-year cardiovascular and coronary mortality are higher in those with ABPI < 0.9
The risk of cardiovascular death increases with decreasing ABPI
ABPI measurement is underutilized and can be usefully incorporated in risk assessment and screening programmes
ABPI measurements are inexpensive, simple and non-invasive
Kornitzer M et al. Angiology 1995;46:211–219.McKenna M et al. Atherosclerosis 1991;87:119–128.Dormandy JA et al. J Cardiovasc Surg 1989;30:50–57
1. Adult Treatment Panel II. Circulation 1994; 89:1333–63. 2. Kannel WB. J Cardiovasc Risk 1994; 1: 333–9. 3. Wilterdink JI, Easton JD. Arch Neurol1992; 49: 857–63. 4. Criqui MH et al. N Engl J Med 1992; 326: 381–6.
*Sudden death defined as death documented within 1 hour and attributed to coronary heart disease (CHD)†Includes only fatal MI and other CHD death; does not include non-fatal MI
Increased risk vs. general population (%)
Early event Myocardial infarction Stroke
Myocardial infarction
Stroke
Peripheral arterial disease
5–7 x (Include death)
3–4 x (Include TIA)
2–3 x (Include angina and sudden death*)
9 x greater risk3
4 x greater risk4
(Include fatal MI and other CHD death)
2–3 x greater risk3
(Include TIA)
Vascular Event Risk
STAGE I(asypmtomatic)
STAGE II(intermitten claudication)
STAGE III and IV(rest pain, serious trophic
disorders)
• Elimination of risk factors
• Lifestyle hygiene
• Vasoactive agents
• Platelet aggregation inhibitors
• Balloon angioplasty in certain specific cases
• Balloon angioplasty
• Surgical treatment:• Thrombo-endarterectomy• Vascular bypass grafts• Lumbar sympathectomy• As a last resort,
amputation
PAD - Management
In shortManagement depends on the stage of disease progression
Prevention of Ischemic Events in Patients at Risk (MI, Ischemic Stroke, PAD)
Life-style management Stop smoking, diet,exercise, avoid heavydrinking
Platelet aggregationinhibitors
Aspirin,1 clopidogrel2
Lipid lowering Statins, fibrates, resins
18L
Antidiabetic drugs Insulin, sulfonylureas
11Antiplatelet Trialists’ Collaboration. BMJ 1994; 308:81-106.Antiplatelet Trialists’ Collaboration. BMJ 1994; 308:81-106. 22CAPRIE Steering Committee. Lancet 1996;348:1329-1339. CAPRIE Steering Committee. Lancet 1996;348:1329-1339.
• Demonstrated benefit in the prevention of atherosclerosis-related arterial thrombosis.
• Main classes of platelet aggregation inhibitors used in peripheral arterial occlusive disease.
Role of Platelet Aggregation Inhibitors
Drug inhibiting arachidonic acid metabolism Aspirin
Drug inhibiting ADP-induced aggregation receptors TiclopidineClopidogrel
COX (cyclo-oxygenase)ADP (adenosine diphosphate)TXA2 (thromboxane A2)
CLOPIDOGREL
ASA COX
ADP
ADP
C
GPllb/llla(Fibrinogen receptor)
Collagen thrombinTXA2
Activation
TXA2
Mode of Action of Clopidogrel1
1. Jarvis B, Simpson K. Drugs 2000; 60: 347–77.
Efficacy of Clopidogrel: Events Prevented (Ischemic Stroke, Myocardial Infarction, Vascular Death)
Time from Randomization (Months)
Eve
nt R
ate/
1,00
0 P
atie
nts/
Yea
r
0 3 6 9 12 15 18 21 24 27 30 33 36
Event Rate per Year
Placebo1
Aspirin2
Clopidogrel2
7.7%
5.8%
5.3%
Based on the APTC findings,1 in a population similar to CAPRIE, for each 1,000 patients treated per year, aspirin can be expected to prevent 19 events and clopidogrel 24.2
19
0
40
80
120
160
5877
53
1Placebo arm extrapolated from APTC meta-analysis. Antiplatelet Trialists’ Collaboration. BMJ 1994;308:81-106, and CAPRIE.
2CAPRIE Steering Committee. Lancet 1996;348:1329-1339. p = 0.043.
24
RECOMMENDATION OF THE USE OF ORAL ANTIPLATELET
IN PATIENTS WITH PAD
- BMJ 2002- PAD Consensus 2003- Meta Analysis 111 Trial
Clinical Problem Pilihan Antithrombotic Intermittent claudication Aspirin (to reduce risk of
stroke and myocardial infarction) atau Clopidrogrel
Diabetes Aspirin (to reduce risk of stroke and myocardial
infraction) or Clopidogrel
Carotid endarterectomy Aspirin or Clopidogrel
BMJ - 2002
PAD is a marker of generalized cardiovascular risk ( Class I )
Antiplatelet agents reduce cardiovascular events and death in
patients with intermittent claudication ( Class I )
Clopidogrel is more effective than aspirin in preventing vascular
events (overall 8.7% proportional reduction in risk). ( Class I )
Aspirin 75-325 mg daily seems effective ( Class I ), and has lower
side effects than as aspirin dose > 325 mg. ( Class II )
PAD Consensus SUMMARY OF EVIDENCE
Eur.J Vasc Endovasc Surg 26-2003
All patients with intermittent claudication or who have had
previous intervention should be considered for long-term anti-
platelet therapy (level A)
The agent used should be either Aspirin 75-325 mg daily
(level A) or Clopidogrel 75 mg per day (level A)
PAD Consensus RECOMMENDATION
Eur.J Vasc Endovasc Surg 26-2003
Oral Antiplatelet Therapy inCerebrovascular Disease,
Coronary Artery Disease, and Peripheral Arterial Disease
A Meta-Analysis of 111 trials : • 22 enrolled patients with TIA or stroke (n=30,619),• 47 enrolled patients with CAD (n=59,821), and • 42 enrolled patients with PAD (n=9,214)
Tran H and Anand SSJAMA ;292:1867-1874
Peripheral Artery Disease
First-Line TreatmentASA or
Clopidogrel
TIA/Stroke ACS TIA/Stroke ACS
ClopidogrelAspirin
Coronary ArteryDisease Present?
Clopidogrelor
Aspirin andClopidogrel
Clopidogrelor
Aspirin and Clopidogrel
orAspirin andExtended-Release
Dipyridamole
Aspirin andClopidogrel
Coronary ArteryDisease Present?
Aspirin andClopidogrel
Aspirin and Clopidogrel
orAspirin andExtended-Release
Dipyridamole
Aspirin andClopidogrel
NoYes Yes No
Intermittent ClaudicationObjectives of Symptomatic Treatment
- Walk further
- Improve quality of life
SUMMARY Atherothrombosis, as manifested by MI, IS, and PAD, is a
prevalent disease that results in severe, disabling, or fatal events:
Myocardial infarction Ischemic stroke Vascular death
Platelet aggregation inhibitors are effective in preventing ischemic events in patients at risk (MI, ischemic stroke, vascular death)
Clopidogrel is more effective than aspirin for preventing ischemic events and has a favorable safety profile1
11CAPRIE Steering Committee. Lancet 1996;348:1329-1339.CAPRIE Steering Committee. Lancet 1996;348:1329-1339.
Peripheral Arterial Disease Guidelines: Management of Patients with Lower Extremity PAD
A Collaboration of the American College of Cardiology, the American Heart Association, the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society for Vascular Medicine and Biology, and the PAD Coalition.
The PAD CoalitionSVMB
Peripheral Arterial Disease Guidelines: Management of Patients with Lower Extremity PAD
A Collaboration of the American College of Cardiology, the American Heart Association, the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society for Vascular Medicine and Biology, and the PAD Coalition.
The PAD CoalitionSVMB
Antiplatelet Therapy
Antiplatelet therapy is indicated to reduce the risk of myocardial infarction, stroke, or vascular death in individuals with atherosclerotic lower extremity PAD.
Aspirin, in daily doses of 75 to 325 mg, is recommended as safe and effective antiplatelet therapy to reduce the risk of myocardial infarction, stroke, or vascular death in individuals with atherosclerotic lower extremity PAD.
Clopidogrel (75 mg per day) is recommended as an effective alternative antiplatelet therapy to aspirin to reduce the risk of myocardial infarction, stroke, or vascular death in individuals with atherosclerotic lower extremity PAD.