1 MMM October 2008 AVAIL ME Project Audit of Venous Thromboembolism Management in Middle East Hospitals Elham Mir,MD MPH Medical Affairs Clinical Operation Head Sanofi Iran

2 Study Design Multinational, observational, cross sectional audit. Trial location MECA Treatment This is an observational audit therefore there are no restrictions on pharmacological and other treatments. The protocol will not interfere with participant’s management. Assessment Schedule The patient files will be assessed during a single visit during the pre- defined audit periods.

3 Objectives Primary: - Impact of educational program on management of patients at risk of VTE, comparing data at baseline, and after 6 months of an educational program. Secondary: - to define factors driving prophylaxis decision in medical and surgical patients - to compare prescriptions modalities v/s hospitals protocols or local/international guidelines - Proportion of at risk hospitalized patients who received effective types of VTE prophylaxis

4 Audit Population All patients hospitalized during the day of the audit Inclusion Criteria - Medical patients 40 years of age or older admitted for treatment of serious acute medical illness - Surgical patients 18 years of age or older undergoing an operation which required general or local anaesthesia lasting at least 45’ Exclusion Criteria - Missing hospital chart - Age less than 18 and underwent a major operation - Patients admitted for treatment of DVT or PE - Patients who refused to give consent to participate in this audit

5 AVAIL ME Extension Article Journal of Thrombosis and Hoemostasis

6 Patients per hospital Hospital Wave 1 patients (n=1084)Wave 2 patients (n=1219) Baghiatollah6151 Bank Melli2750 Shohada Tajrish6137 Emam Reza5657 Erfan6540 Ghaem8679 Imam Hosseiny3594 Imam Khomeiny5471 Laleh5867 Loghman3967 Masih Daneshvari6166 Modaress4867 Oromiyeh6760 Poorsina7887 Rassoul Akram8972 Shahid Sadooghi7374 Shariati4573 Shiraz032 Sina3175 Chamran150 Saadi310

7 Surgical vs Medical Patients ( Wave1: N=1084; wave 2: N =1219) 98.3% Wave 2

8 MMM October 2008 Patients risk factors

9 Patients in medical wards who met ACCP risk criteria (Wave 1: n=395; Wave 2: n=430) VTE risk According to ACCP/ CAPRINI Wave 2

10 Patients in surgical wards who met ACCP risk criteria (Wave 1: n=689; Wave 2: n=789) VTE risk According to ACCP/ CAPRINI Wave 2

11 Patient demographics Wave 1Wave 2 Characteristic Medical (N=395) Surgical (N=689) Medical (N=430) Surgical (N=789) Female sex 187(47.3%)268(38.9%) 184(42.8%)335(42.5%) Age <=40 years years years 75 years + 24(6.1%) 172(43.5%) 124(31.4%) 75(19%) 294(42.7%) 229(33.2%) 108(15.7%) 58(8.4%) 57(13.3%) 187(43.5%) 106(24.7%) 80(18.6%) 345(43.7%) 275(34.9%) 128(16.2%) 41(5.2%) BMI (kg/m2) Underweight (<18.5) Normal ( ) Overweight ( ) Obese( ) Morbid(>40) 20(5.1%) 105(26.6%) 69(17.5%) 28(7.1%) 2(0.5%) 14(2.0%) 141(20.5%) 111(16.1%) 36(5.2%) 4(0.5%) 10(2.3%) 99(23%) 69(16%) 35(8.1%) 3(0.7%) 14(1.8%) 153(19.4%) 125(15.8%) 37(4.7%) 3(0.4%)

12 Caprini risk categories (Blue=Wave 1; Orange=Wave 2)

13 Total Population at VTE risk split medical/surgical Risk category  Wave 1 Low risk N=160 Moderate risk N=176 High risk N=297 Very High N=451 Medical patients 19(4.8%)44(11.1%)106(26.8%)226(57.2%) Surgical patients 141(20.5%)132(19.2%)191(27.7%)225(32.7%) Risk category  Wave 2 Low risk N=177 Moderate risk N=205 High risk N=313 Very High N=524 Medical patients 20(4.7%)52(12.1%)125(29.1%)233(54.2%) Surgical patients 157(19.9%)153(19.4%)188(23.8%)291(36.9%) P<0.001 for wave 1 and wave 2

14 Medical patients: reason for Hospitalization (1) Wave 1Wave 2 Diagnosis N=395%N=430% Renal disease8421.3%9421.9% Other medical condition338.4%6214.4% Acute respiratory disease (non infectious)6616.7%6014% Malignancy (active)4511.4%5913.7% Acute pulmonary infection379.4%4811.2% GI / Hepatobiliary5012.7%4510.5% Infectious disease (non respiratory)246.1%347.9% Ischemic stroke205.1%317.2% Heart failure (NYHA class III/IV)246.1%266%

15 Medical patients: reason for Hospitalization (2) Wave 1Wave 2 Diagnosis N=395%N=430% Other cardiovascular disease184.6%255.8% Endocrine / metabolic174.3%225.1% Hematological diseases51.3%133% Rheumatologic or inflammatory71.8%133% Neurological (excluding stroke)112.8%122.8% Urinary tract infection20.5%71.6% Hemorrhagic stroke61.5%40.9%

16 Surgical Patients: type of surgery (1) Wave 1Wave 2 Surgery N=689%N=789% Other surgery % % Orthopedic trauma % % Hip fracture273.9%557.0% Gynecologic surgery233.3%506.3% Hepatobiliary surgery517.4%425.3% Colon / small bowel surgery588.4%344.3% Gastric surgery355.1%344.3% Urologic surgery253.6%303.8% Knee replacement131.9%263.3% Hip replacement111.6%253.2% Thoracic surgery344.9%253.2%

17 Surgical Patients: type of surgery (2) Wave 1Wave 2 Surgery N=689%N=789% Obstetric surgery182.6%212.7% Rectosigmoid surgery202.9%172.2% Vascular surgery142.0%141.8% Curative arthroscopy81.2%91.1% Surgery minimally invasive Open surgery % 89% % 92.2% Was surgery for cancer? % %

18 Risk factors for VTE (1) Risk factor Wave 1 N=1084 Wave 2 N=1219 No risk factor 45.5%43% Long term immobility 16.9%18.2% Active cancer (diagnosed/treated within 6 months) 17%15.4% Obesity 11.8%12.1% Acute infection 9.1%11.2% Chronic heart failure 8.5%8.4% Central venous catheter 5.7%7.2% Chronic pulmonary disease 8.7%7.2% Cancer therapy (hormonal, chemotherapy) 4.4%6.5% Acute respiratory failure 6.1%5.2% Recent ischemic stroke 4.4%4.8%

19 Risk factors for VTE (2) Risk factor Wave 1 N=1084 Wave 2 N=1219 Acute inflammatory disorder 1.9%2.6% Previous venous thromboembolism 1.3%1.7% Pregnancy within 3 months/post partum 1.9%1.5% Contraceptives / HRT 3.1%1.2% Varicose veins / venous insufficiency 1.6%1.2% Thrombophilia 0.3%0.7% Previous superficial venous thrombosis 0.4%0.1%

20 MMM October 2008 VTE risk management

21 Patients who received any VTE prevention (1) Risk category Low risk N=160 Moderate risk N=176 High risk N=297 Very High N=451 Overall N=1084 Wave 1Eligible for prophylaxis* 089.2%85.2%78.3%70.4% Any VTE prevention* 28.1%36.4%46.1%60.1%47.7% Any drug prophylaxis* 27.5%34.1%44.8%55.9%45.1% Any mechanical prophylaxis* 0.6%2.3%4%10%5.8% Guidelines applied*, ** 70.6%4.5%33.3%34.1%34.5% Guidelines applied*, %4.5%30.3%26.2%30.4% Risk category Low risk N=177 Moderate risk N=205 High risk N=313 Very High N=524 Overall N=1219 Wave 2Eligible for prophylaxis* 085.4%86.6%83.2%72.4% Any VTE prevention* 39.5%55.1%60.1%78.6%64.2% Any drug prophylaxis* 38.4%48.8%55.3%75.8%60.5% Any mechanical prophylaxis 4.6%12.2%8.6%10.1%9.3% Guidelines applied*, ** 54.8%13.7%42.2%55.3%44.9% Guidelines applied*, %13.2%36.4%48.3%40.3% *p<0.001 for differences between risk classes; ** Guidelines were applied with certainty regarding dosing and respect of contraindication; + Taking duration additionally

22 Wave 1Risk category Low risk N=160 Moderate risk N=176 High risk N=297 Very High N=451 Overall N=1084 Medical Any drug* 022.7%40.6%49.1%41.5% Guidelines application*,** 94.7%2.3%20.8% 22.3% Surgical Any drug * 31.2%37.9%47.1%62.7%47.2% Guidelines application *, ** 67.4%5.3%35.6%31.6%35% Wave 2Risk category Low risk N=177 Moderate risk N=205 High risk N=313 Very High N=524 Overall N=1219 Medical Any drug* 35%61.5%53.6%68.2%61.6% Guidelines application*,** 30%7.7%25.6%33%27.7% Surgical Any drug ‡ 38.9%44.4%56.4%81.8%59.9% Guidelines application ‡, ** 58%15%43.6%60.5%47.1% Patients who received VTE prevention (2) *P<0.001; **taking duration, dosing and contraindication respect; ‡ p<0.01

23 Details of management ManagementLow risk N=160Moderate risk N=176High risk N=297Very High N=451Overall N=1084 LMWH* 21.9%24.4%27.9%35%29.4% UFH* 5.6%9.7%17.5%22.4%16.5% VKA 001.3%1.6%1% Fondaparinux %0.1% Other anticoagulant* 001.3%1.8%1.1% ManagementLow risk N=177Moderate risk N=205High risk N=313Very High N=524Overall N=1219 LMWH* 30.5%35.6%39%55.5%44.3% UFH 7.9%10.2%12.8%13%11.7% VKA** 00.5%1%2.7%1.5% Fondaparinux Other anticoagulant* 0.6%3.4%3.2%7.8%4.8% *p<0.001; **p<0.05

24 MMM October 2008 Safety issues

25 Contraindication for prophylaxis Reason for CI (wave 1) Medical N=395 Surgical N=689 All patients N=1084 No contraindications to thromboprophylaxis 82.3%93%89.1% High risk of bleeding 11.1%4.4%6.8% Acute infectious endocarditis 00.1% Hypersensitivity to heparin/LMWH 00.1% Current therapeutic LMWH/UFH/VKA 2.3%0.7%1.3% Previous heparin induced thrombocytopenia 0.8%0.3%0.5% Reason for CI (wave 2) Medical N=430 Surgical N=789 All patients N=1219 No contraindications to thromboprophylaxis 84.7%94.8%91.2% High risk of bleeding 10.2%3.9%6.2% Acute infectious endocarditis 00.1% Hypersensitivity to heparin/LMWH 000 Current therapeutic LMWH/UFH/VKA 0.7%0.3%0.4% Previous heparin induced thrombocytopenia 00.1%

26 Risk factors for bleeding Risk for bleeding (wave 1) Medical N=395 Surgical N=689 All patients N=1084 No risk factors for bleeding upon admission73.4%90.9%84.5% Significant renal impairment 8.1%1.2%3.7% Low platelet count (<100,000 per ml)10.9%2%5.3% Active gastrointestinal bleeding3.8%1.2%2.1% Incracranial haemorrhage1.5%2%1.8% Known bleeding disorder (congenital or acquired)2.5%0.7%1.4% Hepatic impairment (clinically relevant)2.8%01% Oesophageal varices0.8%0.1%0.4% Risk for bleeding (wave 1) Medical N=430 Surgical N=789 All patients N=1219 No risk factors for bleeding upon admission79.3%93.5%88.5% Significant renal impairment 6.7%1.1%3.1% Low platelet count (<100,000 per ml)4%0.5%1.7% Active gastrointestinal bleeding3.3%0.9%1.7% Incracranial haemorrhage0.7%2.3%1.7% Known bleeding disorder (congenital or acquired)3%0.1%1.1% Hepatic impairment (clinically relevant)1.6%0.1%0.7% Oesophageal varices0.2%00.1%

27 Contraindications to VTE prophylaxis Detail (Wave 1) Medical N=395 Surgical N=689 All patients N=1084 Should not be given drug prophylaxis 26.1%9.4%15.5% Should not be given mechanical prophylaxis 18.5%4.6%9.7% Detail (Wave 2) Medical N=430 Surgical N=789 All patients N=1219 Should not be given drug prophylaxis 24.4%9.4%14.7% Should not be given mechanical prophylaxis 14.7%5.3%8.6%

28 Safety data of the population that prohibit VTE prophylaxis Wave 1 Contra Indication to anticoagulationNumber% receiving anticoagulation 16861(36.3%) Contraindication to mechanical prophylaxisNumber% receiving mechanical prophylaxis 1057(6.7%) Wave 2 Contra Indication to anticoagulationNumber% receiving anticoagulation 17973(40.8%) Contraindication to mechanical prophylaxisNumber% receiving mechanical prophylaxis 1059(8.6%)

29 MMM October 2008 In summary…

30 Patients at risk for VTE and receiving ACCP recommended prophylaxis 1042(85.5 %) at Risk for VTE 361(40.9%) received ACCP Recommended prophylaxis respecting duration 160(15.4%) have CI to VTE prophylaxis Wave 2 N= (84.6%) eligible for prophylaxis 177(14.5%) do not need prophylaxis 68(42.5%) received prophylaxis 70(39.5%) received prophylaxis 602(68.3%) received drug prophylaxis 924(85.2 %) at Risk for VTE 195(25.6%) received ACCP Recommended prophylaxis respecting duration 161(17.4%) have CI to VTE prophylaxis Wave 1 N= (82.6%) eligible for prophylaxis 160(14.8%) do not need prophylaxis 56(34.8%) received prophylaxis 45(28.1%) received prophylaxis 389(51%) received drug prophylaxis

31 Concordance between theory and practice Theory Practice Should not receive VTE drug prophylaxis Should receive VTE drug prophylaxis Total Did not receive VTE drug prophylaxis 221(68.8%)374(49%)595(54.9%) Received VTE drug prophylaxis 100(31.2%)389(51%)489(45.1%) Total (Wave 1) 321(100%)763(100%)1084(100%) Theory Practice Should not receive VTE drug prophylaxis Should receive VTE drug prophylaxis Total Did not receive VTE drug prophylaxis 201(59.6%)280(31.7%)481(39.5%) Received VTE drug prophylaxis 136(40.4%)602(68.3%)738(60.5%) Total (wave 2) 337(100%)882(100%)1219(100%) Wave 1: Kappa=0.159; p< Wave 2: Kappa = ; p-value <0.001

32 MMM October 2008 Thank You