Introduction

1. Triple Versus Dual Antithrombotic Therapy in Patients with Atrial Fibrillation and History of Coronary Artery Disease: Insights from the ORBIT-AF Registry Renato D. Lopes, Meena Rao, DaJuanicia N. Holmes, Laine Thomas, Jack Ansell, Gregg C. Fonarow, Bernard Gersh, Alan Go, Elaine M. Hylek, Peter Kowey, Jonathan P. Piccini, Daniel Singer, Paul Chang, Eric D. Peterson, Kenneth W. Mahaffey

2. Introduction • Patients with atrial fibrillation (AF) and coronary artery disease (CAD) are common in clinical practice and antithrombotic therapy is challenging in this population. • Little is known about how these different antithrombotic agents are used in the current era as well as associated clinical outcomes.

3. Methods • ORBIT-AF Registry baseline enrollment (2010–2011): • National, prospective AF outpatient registry (n=176 sites) • Follow up every 6 months for 2 years

4. Methods • We selected the ORBIT-AF population who have a history of coronary artery disease who are on dual or triple antithrombotic therapy. • We stratified by patients on triple antithrombotic therapy or dual therapy at baseline. • Baseline characteristics and medical therapy were compared among different treatment strategies, including patients at different risks for stroke and bleeding. • Cox proportional hazards modeling were used to assess the associations between antithrombotic strategies and outcomes.

5. Study population • Triple therapy: • Oral anticoagulant, thienopyridine and aspirin • Dual Therapy 1: • Oral anticoagulant and one antiplatelet drug • Dual Therapy 2: • Two antiplatelet drugs and no anticoagulant

6. Study population Overall ORBIT-AF Population N=10,132 No history of coronary artery disease N=6,885 Not on triple or dual antithrombotic therapy at baseline N=1552 Patients with CAD on triple or dual therapy N=1695 (16.7%) Dual therapy 1 N=1347(87%) Triple therapy N=152 (9%) Dual Therapy N=1543 (91%) Dual therapy 2 N=196 (13%)

7. Baseline characteristics DT1= OAC plus an antiplatelet agent TT= OAC plus two antiplatelet agents DT2= 2 antiplatelet agents

8. Baseline characteristics DT1= OAC plus an antiplatelet agent TT= OAC plus two antiplatelet agents DT2= 2 antiplatelet agents

9. Baseline characteristics DT1= OAC plus an antiplatelet agent TT= OAC plus two antiplatelet agents DT2= 2 antiplatelet agents

10. Baseline characteristics DT1= OAC plus an antiplatelet agent TT= OAC plus two antiplatelet agents DT2= 2 antiplatelet agents

11. Results • Of patients receiving TT, DT1, and DT2 at baseline, 37.5%, 71.0%, and 61.2% remained on these treatments at 1 year, respectively.

12. Antithrombotic Strategy by CHADS2 Score % of patients on therapy CHADS2 score

13. Antithrombotic Strategy by CHA2DS2VASc Score % of patients on therapy CHA2DS2VASc Score

14. Antithrombotic Strategy by ATRIA Bleeding Score % of patients on therapy Atria bleeding score

15. 1-year Outcomes for triple therapy compared with DT1 and DT2

16. All-cause Hospitalization at 1 Year

17. Rates of MI during 1 year follow-up

18. Limitations • Observational data from prospective national registry. • Treatment groups not randomly assigned. • Low rates of some clinical outcomes e.g. major bleeding.

19. Conclusions • TT is not used in patients with history of hemorrhagic stroke and only about 25% of these patients received a DES in the past year. • Of patients receiving TT at baseline, 37.5% remained on it at 1 year. • New antithrombotic agents are not commonly used in patients receiving TT. • TT use decreases in patients with highest risk of strokeand bleeding. • Patients on triple therapy were more likely to be hospitalized for all cause including bleeding than patients on DT1 or DT2.

20. Thank you

21. Adjustment Variables • All-cause death adjusted for: age, heart rate, systolic blood pressure, BMI, eGFR, sex, cancer, diabetes, COPD, rhythm control, frailty, functional status, level of education, insurance status, congestive heart failure, LAD type, hypertension, stroke or TIA, liver disease, renal disease, GI bleed, and anemia.  • Stroke, non-CNS embolism, TIA, MI or revascularization adjusted for: age, sex, hypertension, stroke or TIA, functional status, family history of AF, peripheral vascular disease, PI/Site specialty, diabetes, liver disease, renal disease, GI bleed, alcohol abuse, prior hemorrhagic diagnosis and anemia. • 1st hospitalization (all-cause) adjusted for: heart rate, systolic blood pressure, diastolic blood pressure, hematocrit, hypothyroidism, obstructive sleep apnea, cancer, dialysis, anemia, frailty, COPD, peripheral vascular disease, prior MI, prior PCI, antiarrhythmic drug use in the past, functional status, congestive heart failure, LAD type, EHRA score, age, sex, hypertension, diabetes, stroke or TIA, liver disease, renal disease, GI bleed, alcohol abuse and prior hemorrhagic diagnosis. • 1st cardiovascular hospitalization adjusted for: age, BMI, sex, heart rate, systolic blood pressure, hematocrit, peripheral vascular disease, obstructive sleep apnea, prior MI, prior PCI, antiarrhythmic drug use in the past, functional status, congestive heart failure, LAD type, AF type, EHRA score, PI/Site specialty, hypertension, diabetes, stroke or TIA, liver disease, renal disease, alcohol abuse, GI bleed and prior hemorrhagic diagnosis and anemia.

22. Outcomes at 1 Year