1. Nancy M Allen LaPointe, Yuliya Lokhnygina, Gillian Sanders, Eric Peterson, and Sana Al- Khatib Is Selection of Antiarrhythmic Drugs for Atrial Fibrillation Consistent with Guideline Recommendations: Results from a Large Contemporary Community Cohort

2. Background Two general treatment strategies for atrial fibrillation – rate vs. rhythm control Two general treatment strategies for atrial fibrillation – rate vs. rhythm control In the rhythm control strategy, guidelines recommend antiarrhythmic drug (AAD) selection based upon presence of concomitant heart disease – HF, CAD, HTN, or none of the above In the rhythm control strategy, guidelines recommend antiarrhythmic drug (AAD) selection based upon presence of concomitant heart disease – HF, CAD, HTN, or none of the above The degree to which clinical practice adheres to the guidelines is largely unknown The degree to which clinical practice adheres to the guidelines is largely unknown Especially in younger patients with atrial fibrillation Especially in younger patients with atrial fibrillation

3. Objective In a large, contemporary, community cohort consisting of AF patients < 65 years of age, assess: In a large, contemporary, community cohort consisting of AF patients < 65 years of age, assess: Proportion receiving AADs (rhythm control strategy) Proportion receiving AADs (rhythm control strategy) Proportion within guideline specified subgroups Proportion within guideline specified subgroups Antiarrhythmic drug use overall and within guideline designated subgroups Antiarrhythmic drug use overall and within guideline designated subgroups

4. Methods: Data Source Thomas Reuters Marketscan ® Commercial Claims and Encounters Database Thomas Reuters Marketscan ® Commercial Claims and Encounters Database Inpatient, outpatient, and prescription claims database from employers and health plans in the US Inpatient, outpatient, and prescription claims database from employers and health plans in the US Includes covered employees and their spouses and dependents Does not include any Medicare claims data Does not include any Medicare claims data All patients < 65 years of age Claims data obtained from 1/1/06 through 12/31/10 Claims data obtained from 1/1/06 through 12/31/10

5. Methods: Overall Study Cohort Inpatient or outpatient encounter with an AF diagnosis (427.31) Inpatient or outpatient encounter with an AF diagnosis (427.31) First AF encounter identified as index AF encounter First AF encounter identified as index AF encounter Age > 30 years Age > 30 years No ventricular arrhythmia diagnosis at any point in time No ventricular arrhythmia diagnosis at any point in time No cardiothoracic (CT) surgery within 30 days of index AF encounter No cardiothoracic (CT) surgery within 30 days of index AF encounter Subsequent AF encounter w/o CT surgery could be selected as index AF encounter Subsequent AF encounter w/o CT surgery could be selected as index AF encounter

6. Methods: Subgroups Patients were then categorized into one of the four subgroups Patients were then categorized into one of the four subgroups Heart failure or Cardiomyopathy. Heart failure or Cardiomyopathy. Coronary Artery Disease Coronary Artery Disease Hypertension Hypertension None of these None of these Category determined by an inpatient or outpatient diagnosis Category determined by an inpatient or outpatient diagnosis In order presented above In order presented above

7. Methods: Antiarrhythmic Drugs and Analysis NDC codes used to identify all oral Class Ia, Ic, and III AAD NDC codes used to identify all oral Class Ia, Ic, and III AAD Prescription claim for > 30 days supply following index date considered AAD use Prescription claim for > 30 days supply following index date considered AAD use Analysis Analysis Describe AAD use with focus on use in subgroups Describe AAD use with focus on use in subgroups Assess consistency between use in clinical practice and guideline recommendations

8. Results: Characteristics of Overall Study Cohort CharacteristicNo AAD n=252, 397 (76%) AAD n=78,877 (24%) Age, median (IQR)56 (50,61)57 (52,61) Men62%69% Region Northeast North Central South West Unknown 17% 28% 38% 16% 2% 11% 30% 41% 16% 2% Type of Health Plan HMO PPO POS Other 17% 64% 9% 11% 15% 66% 9% 10% Index AF encounter Inpatient Outpatient 17% 83% 20% 80%

9. Results: Proportion of index AF encounters with subsequent AAD Use by Year (i.e. “new starts”)

10. Results: Period Prevalence of AAD Use (Quarter)

11. Guideline Recommendations Fuster V et al. Circulation 2011;123:e269-e367 Copyright © American Heart Association

12. Results: Proportion of AF patients in each subgroup with AAD Use by Year (i.e. “new starts”) Incidence of AAD Use by Year of AF index event (i.e. “new starts”)

13. AFib study Population (n= 331,274) No Heart Disease Subgroup n=81,891 (25% ) Patients with AAD n=15,461 (19%) 17,326 AADs Flecainide (33%) Propafenone (22%) sotalol (20%) Amiodarone (14%) Dronedarone (6%) Dofetilide (3%) HTN Subgroup n=110,752 (33%) Patients with AAD n= 24,527 (22%) 28,317 AADs Flecainide (26%) Sotalol (22%) Propafenone (21%) Amiodarone (19%) Dronedarone (8%) Dofetilide (3%) CAD Subgroup n= 77,782 (23%) Patients with AAD n=20,551 (26%) 24,678 AADs Amiodarone (28%) Sotalol (27%) Propafenone (16%) Flecainide (16%) Dronedarone (9%) Dofetilide (4%) HF Subgroup n=60,849 (18%) Patients with AAD n= 18,338 (30%) 22,266 AADs Amiodarone (48%) Sotalol (19%) Propafenone (10%) Dronedarone (9%) Flecainide (9%) Dofetiide (5%) Green=First line Recommendation; Yellow=Second line; Red=Contraindicated

14. Results: Consistency between practice and guidelines HF: Only 53% of AADs used were consistent with guideline recommendations HF: Only 53% of AADs used were consistent with guideline recommendations Between 28% - 47% of AADs were “contraindicated” Between 28% - 47% of AADs were “contraindicated” CAD: Only 31% of AADs used were considered 1 st line and 28% were 2 nd line CAD: Only 31% of AADs used were considered 1 st line and 28% were 2 nd line 32% considered contraindicated 32% considered contraindicated HTN and No heart disease subgroups: HTN and No heart disease subgroups: All AADs used were 1 st or 2 nd line with exception of dronedarone (still not clearly incorporated into US guidelines) All AADs used were 1 st or 2 nd line with exception of dronedarone (still not clearly incorporated into US guidelines)

15. Main Limitations Study cohort included only insured patients from participating health plans Study cohort included only insured patients from participating health plans Results may not be generalizable to uninsured patients or patients from non-participating health plans Results may not be generalizable to uninsured patients or patients from non-participating health plans AAD use was determined by prescription claims AAD use was determined by prescription claims Some patients may not have actually taken the prescribed medication Some patients may not have actually taken the prescribed medication Study relies on the accuracy and completeness of the submitted diagnoses codes Study relies on the accuracy and completeness of the submitted diagnoses codes

16. Summary AAD use is not the dominant strategy in this cohort of patients < 65 years of age AAD use is not the dominant strategy in this cohort of patients < 65 years of age Decreasing incidence of AAD use overall and within subgroups from 2006-2010 Decreasing incidence of AAD use overall and within subgroups from 2006-2010 Increasing prevalence of AAD use overall and within subgroups from 2006-2010 Increasing prevalence of AAD use overall and within subgroups from 2006-2010 Flecainide followed by sotalol had highest prevalence in the overall cohort Flecainide followed by sotalol had highest prevalence in the overall cohort Numerous inconsistencies with guideline recommendations Numerous inconsistencies with guideline recommendations Opportunities for targeted education/awareness Opportunities for targeted education/awareness Additional research Additional research