1. 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.

2. NATURAL HISTORY OF PAD PAD IC WORSENING OF CLAUDICATION 16% CABG 7 % MORBIDITY AMPUTATION 4% NON FATAL CV EVENTS (MI / STROKE) STABLE CLAUDICATION 48% CRITICAL LIMB ISCHAEMIA ASYMPTOMATIC ABI < 0.9 5 YEAR OUTCOME 20-30%

3. RISK FACTORS OF IC MODIFIABLE NON MODIFIABLE OBESITY ATHEROGENIC DIET PHYSICAL INACTIVITY HYPERTENSION (2-3 FOLD) D.M. (2-4 FOLD) DISLIPIDEMIA (2 FOLD) CIGERATTE SMOKING (2- 7 FOLD) THROMBOGENIC OR HAEMOSTATIC STATE AGE MALE SEX FAMILY HOISTORY OF PREMATURE CHD

4. 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 SEVERE IC * X-RAY OF LEG DOPPLER FLOW STUDY OF LIMB VESSELS

5. 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

6. CILASTOZOLE – MECHANISM OF ACTION 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

7. 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

8. COMPARISON BETWEEN CILOSTAZOLE & PENTOXYPHYLLINE ParemetersCilostazolePentoxyphylline Clinical EfficacyAll 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 medicineBenefits are shown in severe extensive clinical development programms including RCT Clinical benefits are not well established. Improvement in quality of lifePatients experience improved functional status. No improvement on QOL or community based functional status. ComplianceBetter than Pentoxyphylline

9. 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.

10. 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