Gandhi S, Dorian P, Tardif JC, Steg PG, Huynh T, Wong GC, Love MP, Jervis K, Goodman SG,

1. High use of guideline-recommended therapies in Canadian outpatients with stable coronary artery disease: insights from the ProspeCtive observational LongitudinAl Registry oF patients with stable coronary arterY disease (CLARIFY) Gandhi S, Dorian P, Tardif JC, Steg PG, Huynh T, Wong GC, Love MP, Jervis K, Goodman SG, for the (ProspeCtive observational LongitudinAl Registry oF patients with stable coronary arterY Disease) CLARIFY Registry Investigators From the Terrence Donnelly Heart Centre, St Michael's Hospital, University of Toronto and the Canadian Heart Research Centre, Toronto, ON; MHI Research Centre, Montreal Heart Institute, Unjversity of Montreal, Montreal, QC; Recherche Clinique en Athérothrombose, Unité INSERM U698, Centre Hospitalier Bichat-Claude Bernard, Université Paris Diderot, Paris, France; McGill University Health Centre, Montreal, QC; Vancouver General Hospital, University of British Columbia, Vancouver, BC; Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS; Servier Canada Inc, Laval, QC.

2. Disclosures • All CLARIFY data was collected and analyzed by the independent academic statistics centre at the Robertson Centre for Biostatistics, University of Glasgow, UK • Nicola Greenlaw provided the statistical analysis for this abstract • Additional Canadian data regarding medication use was collected by the Health Research Centre (AHRC) at St. Michael’s Hospital, University of Toronto • The study was designed and conducted by the investigators, supported by research grants from Servier Canada and France. • The sponsor had no role in study design, data collection and analysis, decision to publish, or writing of the abstract, but did assist with the set-up and management of the study in each country.

3. Conflicts of Interest Consulting fees, honoraria and/or research: S. Gandhi, None P. Dorian, Servier Canada Inc J.C. Tardif, Servier Canada Inc P.G. Steg, Astra Zeneca, Bayer, BoehringerIngelheim, Bristol Myers Squibb, Daiichi Sankyo Lilly, Eisai, GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, Roche, Sanofi Aventis, Servier, The Medicines Company, NYU School of Medicine, Aterovax T. Huynh, Servier Canada Inc G.C. Wong, Servier Canada Inc M.P. Love, AstraZeneca, Eli Lilly, Bristol-Myers Squibb and Sanofi Aventis K. Jervis, Servier Canada Inc S.G. Goodman, Servier Canada Inc

4. Coronary Artery Disease (CAD) • Evidence based therapy for secondary prevention for patients with CAD includes: • Antithrombotics • Beta-blockers • ACE inhibitors and ARBs • Lipid-lowering therapy • Previous analysis from Canadian high vascular risk registries (n=9810 from >500 MDs; 2001-2004) demonstrated underutilization of guideline-recommended therapies, in part due to physician underestimation of cardiovascular risk Smith et al Circulation 2011;124:2458-73 Tsang et al Am J Cardiol 2008;102:1142-45

5. ProspeCtive observational LongitudinAl Registry oF patients with stable coronary arterY disease (CLARIFY) • Initiated to improve knowledge about patients with stable CAD from a broader geographic prospective • Main objectives • define contemporary stable CAD outpatients in terms of their demographic characteristics, clinical profiles, management, and outcomes; identify gaps between evidence-based recommendations and treatment; and investigate long-term prognostic determinants in this population Steg Eur Heart J 2009;11(suppl D):D13-D18

6. Purpose of this Analysis • To • describe the use of evidence-based therapy for the Canadian cohort of CLARIFY • understand the specific reasons why some guideline-recommended therapies are not implemented in order to provide insight into the contemporary management of the Canadian stable CAD population

7. CLARIFY • Prospective, observational, longitudinal registry • Consecutive outpatients with stable CAD from 45 countries in Europe, the Americas, Africa, Middle East, and Asia/Pacific enrolled Nov 2009 – July 2010 • Continued follow-up for 5 years • Collection of standardized data on e-CRF • Complete data audits in 5% randomly selected sites Steg Eur Heart J 2009;11(suppl D):D13-D18

8. Enrollment criteria • Eligible patients had stable CADdefined as at least one of the following (not mutually exclusive): • Documented MI > 3 months before enrolment • Angiographic demonstration of coronary stenosis > 50% • Chest pain with evidence of myocardial ischemia (stress ECG) • PCI or CABG > 3 months before enrolment • Exclusion criteria: • Hospital admission for CV reasons (including revascularization) in the past 3 months • Planned revascularization • Conditions hampering the participation or the 5-year follow-up e.g., limited cooperation, limited legal capacity, serious non-CV disease or conditions interfering with life expectancy (e.g. cancer, drug abuse) or severe other CV disease (e.g. advanced HF, severe valve disease, history of valve repair/replacement) Steg Eur Heart J 2009;11(suppl D):D13-D18

9. Medications • We prospectively designed an additional case report form for Canadian patients to capture reason(s) why specific CV treatments were not prescribed. • The patient’s physician was to provide at least one reason why the patient was not currently treated with a therapy, including for antiplatelet agents, beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), and lipid-lowering drugs. • The reasons included drug-specific: • allergy • contraindication • intolerance • not compliant/refused • clinical trial evidence or current guidelines do not support use • other

10. Canadian Specific Medication Data – Reasons Why Not

11. Worldwide distribution 33 284 patients enrolled in 46 countries Western Europe Austria 425 Belg/Luxem 577 Denmark 133France 2428 Germany 2250 Greece 559 Ireland 190 Italy 2114 Netherlands 206 Portugal 949 Spain 2257 Switzerland 291 UK 2351 Central/Eastern Europe Bulgaria 172 Poland 1004 Czech Rep 393 Romania 502 Hungary 344 Slovakia 183 Latvia 120 Slovenia 81 Lithuania 214 North America Canada 1232 Russia/Ukraine Russia 2248 Ukraine 777 Asia Brunei (Incl. in Mal) China 2622 India 809 Korea 1020 Malaysia 380 Singapore 113 Thailand 693 Vietnam 506 Middle East Bahrain 750 Kuwait Oman Qatar Saudi Arabia 761 UAE Central America Mexico 1342 West Indies 368 South America Argentina 234 Brazil 291 Africa South Africa 543 Australasia Australia 833

12. Canadian distribution 1232 patients enrolled in 9 provinces Newfoundland n=10 (1%) Quebec n=357 (29%) British Columbia n=186 ( (15%) Manitoba n=54 (4%) Alberta n=88 (7%) Saskatchewan n=25 (2%) Ontario n=461 (37%) New Brunswick n=30 (2%) Nova Scotia n=21 (2%)

13. Enrollment by Canadian Physicians

14. Selected Characteristics

15. Recent Vital Signs and Lipid Profile

16. Reimbursement Status for Medication 51% (n=630) 42% (n=515) 40% (n=12 629) 37% (n=11 658) 24% (n=7 661) 7% (n=84)

17. Selected Medications

18. Reasons why not taking medication in Canadian cohort

19. Summary • Most Canadian patients have financial medication coverage • Most Canadian patients are on guideline recommended therapies • Among the patients not on guideline recommended therapy, underestimation of risk (i.e. “not indicated”) is low

20. Limitations • Recruited physicians and enrolled patients on a voluntary basis, introducing selection bias • Practice of these physicians likely different from that of all physicians, we speculate that our participating physicians are more adherent to guidelines • The case report form may not adequately identify patients in whom such treatments may be inappropriate or less than ideal despite general evidence-based guideline recommendations

21. Conclusions • In contrast to previous Canadian registries, the CLARIFY cohort has very high use of guideline-recommended therapies in stable CAD patients • >90% reported partial/full financial coverage for their medications • The number of patients not receiving evidence-based therapies due to apparent underestimation of risk (i.e., “not indicated” despite the presence of CAD) was particularly low for antiplatelet, beta-blocker, and lipid lowering therapies

22. CLARIFY Investigators British Columbia:CE Biglow, Qualicum Beach; D Ezekiel, Vancouver; DE Manyari, Surrey; FM Villasenor, Maple Ridge; GF Vaz, Vernon; K Lai, Nanaimo; MMW Yeung, Richmond; M Fagan, Langley; MA Fazil, Duncan; P Wong, Richmond; RS Collette, Burnaby; SK Wong, Vancouver; TL Orenstein-Lyall, Richmond; TH Ashton, Penticton; WK Son, Chilliwack. Alberta:A Bailey, Spruce Grove; APT Wong, Edmonton; E Liu, Calgary; JL Myburgh, Sylvan Lake; RR Singh, Calgary; S Varma, Calgary; SH Chiu, Edmonton; W Healley, Calgary. Saskatchewan:FB Ramadan, Moose Jaw; M Shamsuzzaman, Regina. Manitoba:I Rodriguez Marrero, Brandon; M Czarnecka, Winnipeg; W Czarnecki, Winnipeg. Ontario: AS Pandey, Cambridge; AK Gupta, Toronto; AM Kushner, Etobicoke; A Grover, Mississauga; AI Bakbak, Oshawa; B Sullivan, Hamilton; B Lubelsky, North York; D Kennedy, Simcoe; DS Wong, London; DR Spink Jr, Peterborough; D Spensieri, Woodbridge; FJ Nasser-Sharif, Port Perry; GM Fullerton, Woodstock; GE Vertes, Scarborough;GW Kellam, Prescott;GA Antoniadis, Wingham; HA Boyrazian, Scarborough; HE Harlos, Elmvale; H Sullivan, Hamilton; H Kim, St Catharines;J Vavougios, Toronto;JM Cherry, Scarborough; JYM Cha, Oshawa; JS Bhatt, Brockville; J Gold, North York; JCS Leong, Etobicoke; J Berlingieri, Burlington; J Campbell, Belleville; K Yared, Scarborough; LP Quinn, Oshawa; MSC Ho, Toronto; P Morra, Oshawa; QH Tran, Chatham; R Patel, Scarborough; RS Grewal, Ottawa; S Pallie, St Catharines; V Martinho, Ottawa; W Nisker, Burlington; YK Chan, Niagara Falls.

23. CLARIFY Investigators (cont’d) Quebec: A Belanger, Courcelette; A Kokis, Montreal; A Roy, Laval; B Roy, Beauceville; C Constance, Montreal; D Savard, Montreal; D Rouse, Saint-Jerome; D Saulnier, Levis; F Perreault, Sainte-Anne-De-Bellevue; G Levesque, Saint-Pascal; G Verret, Saint-Raymond, QC; G Boutros, Laval; G Sabe-Affaki, Pointe Claire; G Lafrance, Quebec; G Brouillette, Lasalle; G Brisson, Laval; G Chouinard, Quebec; JP Lavoie, Longueuil; J Robb, Sherbrooke; L Lasalle, Verdun; M Leclair, Anjou; P Talbot, Quebec; S Garg, Montreal; TT Nguyen, Gatineau; P Belisle, Chicoutimi; P Lebouthillier, Quebec; R Chehayeb, Greenfield Park; R Gendreau, Laval; TA Cieza Lara, Chicoutimi; Y Pesant, Saint-Jerome. New Brunswick:G Searles, Saint John; JF Baril, Dieppe; P Clavette, Edmundston. Nova Scotia: HB Matheson, Halifax; N Giacomantonio, Halifax. Newfoundland: J Janes, Mount Pearl.

24. Back up Slides

25. Enrollment by Canadian Physicians

26. Symptoms reported with beta-blocker Use (Previous or Current)

27. Reimbursement Status for Medication

28. physicians were instructed to enroll consecutive patients (although this cannot be verified), and the wide inclusion criteria, together with limited exclusion criteria, makes it likely that a broad range of patients were included