GARFIELD-AF Investigators Meeting Johannesburg, 27 th October 2017 - PowerPoint PPT Presentation

GARFIELD-AF Investigators’ Meeting Johannesburg, 27 th October 2017

08:30 Registration and coffee Welcome 09:00 Overview of findings from the global Professor the Lord Kakkar Agenda data set 09:30 Global status update Gloria Kayani Clinical perspectives of atrial fibrillation from South Africa. 10:15 Professor Barry Jacobson GARFIELD-AF: How does South Africa compare with rest of the world?  GARFIELD-AF Risk Score: Can GARFIELD help improve risk stratification for patients with 10:45 Professor the Lord Kakkar AF?  GARFIELD-AF: Health economics analysis 2

Thrombosis Research Institute: Welcome Professor the Lord Kakkar and Prof Barry Jacobson 3

Thrombosis Research Institute (TRI) • TRI is an independent global academic organisation • We have a 45 year track record and are dedicated to working in thrombosis and our pioneering research programmes across the world, continue to provide breakthrough solutions • We undertake research though a network of 2500 centres in 40 countries 4

Garfield-AF: • Past and Present

GARFIELD-AF journey – review of how far we have come • 1-year follow- 2012 2016 up locked for • First patient • Cohort 1 all prospective in baseline patients • Methods • 2-year paper paper outcomes • Treatment published published paper patterns paper published published 2009 2013 2017

Mission statement • To enhance understanding of the burden of thromboembolic stroke and identify opportunities for the incorporation of innovations designed to improve safety, outcomes and utilisation of healthcare resources • The unique design and methodology of GARFIELD-AF will provide representative, real-world insights, and will clarify AF treatments and outcomes for patients, clinicians and healthcare providers as they evolve over time • GARFIELD-AF is governed by the highest academic and ethical standards in the generation, dissemination, and communication of its research findings

Why did we need a global AF registry? • Uncertainty persisted about how AF is managed in the real world and how these treatment patterns affect patient and population outcomes • This was a problem in relation to treatment guidelines, in specific patient populations, across various care settings • There was a large burden of preventable stroke in patients with AF and historical underutilization and poor VKA control for stroke prevention in AF • NOACs had been introduced for stroke prevention in AF 8

GARFIELD program – where we are today • This year we reached a momentous milestone, completing patient enrolment across the GARFIELD programme • Between GARFIELD-AF and GARFIELD-VTE we have: • Recruited 68,140 patients in 39 countries • Captured over 100,000 prospective patient years and will soon have more than 150,000 • Our data concordance remains at a remarkable level above 95%

Prospective registries in AF Registry Population size Patient enrolment – key design features Follow-up duration • GARFIELD-AF 1 57,262 Prospective patients (approx.52,000) enrolled <6 weeks after AF diagnosis in 5 sequential ≥2 years, up to 8 years cohorts • Retrospective patients (approx. 5,000) enrolled 6 – 24 months after diagnosis GARFIELD- AF’s unique • ≥1 additional investigator -determined risk factor for stroke study design • GLORIA-AF 2 Target: 56,000 Prospective patients enrolled <3 months after AF diagnosis in 3 phases 0 – 3 years • To date: >38,000 CHA 2 DS 2 - VASc score ≥1 Phase 1 (pre-NOAC): none Phase 2 (Dabigatran): 2 years Phase 3 (VKA/NOAC): 3 years • ORBIT-AF I 3 10,132 Incident or prevalent AF ≥2 years • Patients excluded if anticipated life expectancy <6 months • ORBIT-AF II 4 13,415 Prospective patients enrolled <6 months after AF diagnosis; or enrolled <3 months after ≤2 years initiation or transition to a NOAC • Patients excluded if anticipated life expectancy <6 months • PREFER in AF 5 7243 Prospective patients enrolled <12 months after AF diagnosis 1 year 1. Kakkar AK et al. Am Heart J. 2012;163:13-19 e1; 2. Huisman MV et al. Am Heart J. 2014 Mar;167(3):329-34; 3. Piccini JP et al. Am Heart J. 2011;162:606-612.e1; 4. Steinberg BA. Am Heart J. 2014;168:160-7. 5. Kirchhof P et al. Europace. 2014;16:6-14.

GARFIELD-AF – looking ahead • There is now only 1 year of the programme remaining as we complete the follow-up period of our final cohorts • Already we have produced and published many excellent analyses, including the GARFIELD- AF risk score • The first manuscript from the collaboration with ORBIT-AF is about to be published • GARFIELD-AF is also generating insights on the management and outcomes of patients with comorbid conditions

Garfield-AF: • Early Insights

Evolution in baseline treatment for patients enrolled in sequential cohorts of GARFIELD-AF VKA±AP FXaI/DTI±AP AP None 100 Proportion of patients on treatment, % 80 60 4.2 13.8 26.3 37.3 43.1 40 71.2% 57.4% 20 0 Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 2010 – 2011 2011 – 2013 2013 – 2014 2014 – 2015 2015 – 2016 Cohorts 1 – 5, N=52,081; AP, antiplatelet; DTI, direct thrombin inhibitor; FXaI, factor Xa inhibitor; VKA, vitamin K antagonist

Event rates for data collected prospectively starting from the date of the first study visit up to 1 year Retrospectively enrolled cohort Prospectively enrolled cohort 5.0 Rate (95% CI) per 100 person-years 4.5 4.0 4.05 3.5 3.0 3.04 2.5 2.0 1.5 1.34 1.0 1.07 0.82 0.5 0.72 0.0 Stroke/SE Major bleeding All-cause mortality Stroke/SE Major bleeding All-cause mortality Enrolment Retrospective Prospective Retrospective Prospective Retrospective Prospective Person-years 3432.7 5144.1 3466.7 5146.3 3491.1 5166.1 Events 46 55 25 42 106 209 Cohort 1: retrospectively enrolled (n=5069), prospectively enrolled (n=5501)

One-year event rates following a new diagnosis of AF Outcome Events Event rate 95% CI (per 100 person-years) All-cause mortality 2103 4.38 4.20 to 4.57 Cardiovascular 789 1.64 1.53 to 1.76 Non-cardiovascular 771 1.61 1.50 to 1.72 Undetermined cause 543 1.13 1.04 to 1.23 Stroke/systemic embolism 650 1.36 1.26 to 1.47 Major bleeding 407 0.85 0.77 to 0.94 Acute coronary syndromes 378 0.79 0.71 to 0.87 Congestive heart failure 1052 2.22 2.09 to 2.35 Cohorts 1 – 5, N=52,081

Event rates by country (0.0 = global mean) after adjustment of all factors in the model Fox KAA, presentation at Satellite Symposium, ESC Congress 2016 Fixed effects included in the models: gender, age group, diabetes, hypertension, congestive heart failure, vascular disease, previous stroke*, previous bleed**, ethnicity, smoke, type of atrial fibrillation, moderate-to-severe chronic kidney disease. *Not included in the model for major bleeding. **Not included in the model for stroke/systemic embolism (SE). ARG, Argentina; AUS, Australia; AUT, Austria; BEL, Belgium; BRA, Brazil; CAN, Canada; CHE, Switzerland; CHL, Chile; CHN, China; CZE, Czech Republic; DEU, Germany; DNK, Denmark; EGY, Egypt; ESP, Spain; FIN, Finland; FRA, France; GBR, United Kingdom; HUN, Hungary; IND, India; ITA, Italy; JPN, Japan; KOR, South Korea; MEX, Mexico; NLD, Netherlands; NOR, Norway; POL, Poland; RUS, Russia; SGP, Singapore; SWE, Sweden; THA, Thailand; TUR, Turkey; UAE, United Arab Emirates; UKR, Ukraine; USA, United States of America; ZAF, South Africa. EB, empirical Bayes estimate.

Causes of death during first-year follow-up Events % Cardiovascular deaths (n=789) 1 Congestive heart failure 262 33.2 Sudden or unwitnessed death 127 16.1 Myocardial infarction 89 11.3 Ischaemic stroke 86 10.9 Other 223 28.3 Non-cardiovascular deaths (n=771) 2 Malignancy 233 30.2 Infection/sepsis 155 20.1 Respiratory failure 142 18.4 Accidental/trauma 17 2.2 Other 221 28.7 Cohorts 1 – 5, N=52,081; 1 missing: 2 deaths; 2 missing: 3 deaths

Types of stroke during first-year follow-up Events % Stroke (not including systemic embolism) 585 100 Primary ischaemic stroke 406 69.4 Primary intracerebral haemorrhage 71 12.1 Undetermined 108 18.5 Cohorts 1 – 5, N=52,081

Integrated care is needed for comorbid conditions with common risk factors and pathologies CAD ACS Electrical remodel- Diabetes Increasing age ling Myocyte Vascular damage pathology AF Vascular disease Heart failure Impaired Atrial cardiac dilation function Kidney disease Stroke/TIA Altered Prothrom- haemo- botic dynamics state ACS, acute coronary syndromes; AF, atrial fibrillation; CAD, coronary artery disease; TIA, transient ischaemic attack

GARFIELD-AF is providing important insights into registry design Retrospectively enrolled cohort Prospectively enrolled cohort

Differences in type of AF between retrospectively and prospectively enrolled patients Retrospectively enrolled Prospectively enrolled 50 44.8 45 40 Proportion of patients (%) 36.3 35 30.9 30 24.5 25 19.4 20 16.5 14.1 13.3 15 10 5 0 Unclassified Paroxysmal Persistent Permanent Type of AF

Thrombosis Research Institute: Global Operations Update Gloria Kayani 22