Transcript pad and vascular events

PAD AND VASCULAR EVENTS
 IC AS A DISEASE OFTEN REMAINS UN RECOGNISED. AS
HIGH AS 75% OF PEOPLE WHO HAVE IC DO NOT SEEK
MEDICAL HELP SINCE MANY PEOPLE TAKE LEG PAIN AS A
NATURAL CONSEQUENCE OF AGEING.
 PAD OFTEN CO EXIST WITH CORONARY &
CEREBROVASCULAR ATHEROSCLEROTIC DISEASE.
 RISK OF CARDIOVASULAR MORBIDITY & MORTALITY
(30%) FAR EXCEEDS THAT OF SEVERE LIMB ISCHAEMIA
OR LIMB LOSS 4%.
 NON FATAL CV EVENTS, MI & STROKE ARE SEEN IN
AROUND 20% PATIENTS.
NATURAL HISTORY OF PAD
PAD
ASYMPTOMATIC
ABI < 0.9
CRITICAL
LIMB
ISCHAEMIA
IC
20-30%
NON FATAL
CV EVENTS
(MI / STROKE)
MORBIDITY
5 YEAR OUTCOME
STABLE
CLAUDICATION
48%
WORSENING
OF
CLAUDICATION
16%
AMPUTATION
4%
CABG
7%
RISK FACTORS OF IC
MODIFIABLE
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OBESITY
ATHEROGENIC DIET
PHYSICAL INACTIVITY
HYPERTENSION (2-3
FOLD)
D.M. (2-4 FOLD)
DISLIPIDEMIA (2 FOLD)
CIGERATTE SMOKING (27 FOLD)
THROMBOGENIC OR
HAEMOSTATIC STATE
NON MODIFIABLE
• AGE
• MALE SEX
• FAMILY HOISTORY OF
PREMATURE CHD
DIAGNOSIS - IC
• DETAILED HISTORY
• PHYSICAL EXAMINATION – ESPECIALLY OF PULSE
CONDITION OF SKIN SURFACE, * ULCER, EVIDENCE OF
ATHEROSCLEROTIC DISEASE IN OTHER ORGANS LIKE
CAROTID BRUIT, ABDOMINAL BRUIT ETC.
ANKLE BRACHIAL INDEX = ANKLE B.P. / BRACHIAL B.P.
(NON-INVASIVE ACCURATE PREDICTIVE)
> 1.3 – NON COMPRESSABLE
0.9 – 1.3 => NORMAL
0.4 – 0.9 => MILD TO MODERATE IC
< 0.4 => SEVERE IC
• * X-RAY OF LEG
• DOPPLER FLOW STUDY OF LIMB VESSELS
CILOSTAZOLE ACTION ON PLATELETS
• INHIBITS PLATELETS AGGREGATION
INDUCED BY THROMBIN, ARACHAIDONIC
ACID, EPINEPHRINE, SHEER STREES,
COLLAGEN, ADP
• CILASTOZOLE
INHIBITS PHOSPHODIASTERASE III
INTRACELLULAR cAMP
INTRACELLULAR CALCIUM
INHIBITS PLATELET AGGREGATION
CILASTOZOLE IS 10 TO 30 TIMES MORE POTENT
THAN ASPIRIN IN INHIBITING PLATELET
AGGREGATION
CILASTOZOLE – MECHANISM OF ACTION
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VASODILATOR
ANTI PLATELET ACTIVITY
ANTITHROMBOTIC ACTIVITY
VASCULAR ANTI PROLIFERATIVE EFFECT
CORRECTION OF VASCULAR ENDOTHELIAL
FUNCTION
• LIPID LOWERING EFFECT – TG BY 15.8% HDLC
BY 12.8% APO-A1 BY 32% RLP-C BY 26%
• PENTOXYPHILLINE ONLY IMPROVES
HAEMORHEOLOGY
CILOSTAZOLE IN PATIENTS WITH TYPE 2 DM
• DM IS ASSOCIATED WITH HIGHER RISK OF PAD
• PAD IN DM IS MORE SEVERE AND RAPIDLY
PROGRESSIVE FROM NON DIABETICS
• EARLY DETECTION OF PAD IN DM IS DIFFICULT DUE
TO PRESENCE OF NEUROPATHY, EARLY
CALCIFICATION OF ARTERIES AND ANKLE PRESSURE
ARE NOT REDUCED
• GOOD GLYCEMIC CONTROL ONLY PROVIDES MODEST
BENEFITS IN PREVENTING THE COMPLICATIONS AND
OCCURRENCE OF PAD
• ATTENTION TO OTHER RISK FACTORS ARE NEEDED
• CILASTOZOLE IS HIGHLY EFFECTIVE FOR ITS
MULTIBENIFICIAL ACTIVITIES
COMPARISON BETWEEN
CILOSTAZOLE & PENTOXYPHYLLINE
Paremeters
Cilostazole
Pentoxyphylline
Clinical Efficacy
All Studies reveal highly significant
improvement in exercise performance &
walking distance. Improvement in limb
perfusion especially diabetics, marked
improvement in associated risk factors &
PT compliance
Benefits are questionable.
Evidence based medicine
Benefits are shown in severe extensive
clinical development programms
including RCT
Clinical benefits are not well
established.
Improvement in quality of life
Patients experience improved functional
status.
No improvement on QOL or
community based functional
status.
Compliance
Better than Pentoxyphylline
• Cilostazole – further research expectations –
extended benefits.
• Prevention of recurrent stroke in some
patients.
• Under investigations for prophylaxis of
primary & secondary stroke as well as
Brady arrhythmias.
CONCLUSION
• Cilostazole with its unique combination of
anti platelets, vasoditatory antithrombotic ,
antiprolifertative effects and favourable
effects on vascular endothelium, lipid
lowering effect will be an important break
through in improving symptoms & quality
of life in patients with IC