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PLAVIX Update Management of POAD Current Meta-Analysis of Antiplatelet R BOWO PRAMONO PAPDI CABANG YOGYAKARTA

Plavix Joa-joa Cafe 2 Mei 2013

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Page 1: Plavix Joa-joa Cafe 2 Mei 2013

PLAVIX

Update Management of POADCurrent Meta-Analysis of Antiplatelet

R BOWO PRAMONO

PAPDI CABANG YOGYAKARTA

Page 2: Plavix Joa-joa Cafe 2 Mei 2013

ATHEROTHROMBOTIC

Atherosclerotic Plaque

Rupture Plaque

Thrombus in to atheroma

Thrombus Formation

CHRONIC ISCHEMIA

Stable plaque

ACUTE EVENT

Occlusion

Emboli

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Apa itu Peripheral Arterial Disease?

Arteri pada bagian extremities terjadi stenosis atau tersumbat karena atherosclerosis

Biasanya arteri yang besar atau sedang

Umunya didaerah percabangan

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Lifestyle / Gaya Hidup

• Perokok +++Resiko utama atherosclerosis pada kaki dan coronary arteries

• Diet yang tidak tepat (fats)

• lifestyle

• Stress?

Siapa yang terkena resiko PAD?

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Faktor yang tidak bisa dirubah

• Usia +++

• Laki laki ++

• Faktor Genetik

Siapa yang terkena resiko PAD?

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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.

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The Ankle-Brachial Index

Lower extremity systolic pressure

Brachial artery systolic pressureABI =

Normal ABIICCLI

0.9 - 1.3<0.90<0.50

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Doppler Ultrasound

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• 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

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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

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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

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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.

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Stage II: Intermittent Claudication

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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

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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

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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

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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

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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.

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• 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

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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.

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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

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RECOMMENDATION OF THE USE OF ORAL ANTIPLATELET

IN PATIENTS WITH PAD

- BMJ 2002- PAD Consensus 2003- Meta Analysis 111 Trial

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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

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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

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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

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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

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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

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Intermittent ClaudicationObjectives of Symptomatic Treatment

- Walk further

- Improve quality of life

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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.

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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

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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.

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