Geriatric Grand Rounds

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1 Geriatric Grand Rounds Tuesday, April 13, 21 12: noon Dr. Bill Black Auditorium Glenrose Rehabilitation Hospital In keeping with Glenrose Rehabilitation Hospital policy, speakers participating in this event have been asked to disclose to the audience any involvement with industry or other organizations that may potentially influence the presentation of the educational material. Disclosure will be done both verbally and using a slide or handout.

2 An Update on Atrial Fibrillation Management ID CC Hx Dx 68 M Case palps x 1 yr ; weekly; 1-72hrs associated with mild SOB & dizziness HTN (26) Echo - sl. dilated LA Holter - brief runs of AF Defining significance 3s 2min 6min/wk stroke prevention symptom relief heart rate control

3 every 45 seconds every 3 minutes Would you start Warfarin? Congestive heart failure 1 Hypertension 1 Age 75 1 Diabetes 1 Stroke or TIA ASA ASA or Warfarin Warfarin Annual Stroke Risk

4 66% 25% vs. Problems with Warfarin INR <2 or >3 ~⅓ of time in trials ~ 2% of eligible pts have contraindications Not prescribed in > 5% eligible pts 2% 1%?% +?% PLAVIX AF permanent or 2 episodes in prior 6 mo + risk factor age 75 HTN TIA, CVA, embolism EF <45% PVD age CAD or DM

5 W.5 Risk of Stroke RR = 1.45 (p<.1) ASA + clopidogrel vs. anticoagulation (2.-3.) CHADS2 = 2. Hazard Rates ASA & Plavix Warfarin years Risk of Bleeding.5 RR = 1.6 (p=.67) INR Control.4 Hazard Rates Warfarin ASA & Plavix years % 21% 15% < 2. > 3.

6 A If CHADS2 >1, warfarin is better than ASA & Plavix ASA + clopidogrel vs. ASA CHADS2 = 2. Physician s Decision 23%.4 Primary Outcome HR =.89 (p=.14) Risk of Bleeding* 51% *unable to comply with INR (28%) risk of falls (1%) severe HTN (3%) Hx of serious bleed (6%) EtOH, PUD, NSAID use, low plts (6%) Patient Preference 26% Hazard Rates. ASA Clopidogrel + ASA 2 4 years

7 .15 Risk of Stroke HR =.72 (p<.1) Hazard Rates ASA Clopidogrel + ASA. 2 4 years major bleeding - RR 1.57 (GI - RR 1.96) (ICH - RR 1.87) RR minor (p<.1) vs. ASA CVA ICH ECH Warfarin 38% 7% 128% ASA/clopidogrel 28% 51% 87% If CHADS2 >1, and I can t use warfarin, ASA & Plavix is better than ASA alone (as long as they aren t bleeders!)

8 vs. Triple Therapy ASA + Clopidogrel + Warfarin Triple Therapy 127 pts (224 lesions - 5% BMS; 5% DES) overall bleeding 7.1% major bleeding 4.7% half of these were fatal...⅔ within the first month Watch very carefully when pts are on triple therapy

9 Stroke or Systemic Embolism Dabigatran better Warfarin better Dabigatran 11 vs. Warfarin non-inferior Dabigatran vs. Warfarin (Pradax) AF + 1 risk factor Dabigatran 15 vs. Warfarin non-inferior & superior HR (95% CI).4 Hemorrhagic Stroke RR = (p<.1) Monthly costs $285.3 * Hazard Rates Warfarin Dabigatran 2.5 Years $4.1 ASA 81mg OD $15.47 Warfarin 5mg OD $12.59 Clopidogrel 75mg OD Dabigatran 11mg bid

10 Dabigatran is a very promising alternative to Warfarin in AF stroke prevention symptom relief heart rate control No difference between rate & rhythm control...in properly selected patients works 9% of the time

11 amiodarone sotalol propafenone flecainide dronedarone O (CH 2 ) 3 CH 3 used for: AF CH 3 SO 2 HN O O(CH 2 ) 3 N (CH 2 ) 3 CH 3 (CH 2 ) 3 CH 3 absolutely avoided in: NYHA IV CYP 3A4 drugs (-ozoles, cyclosporin, Biaxin) liver failure, brady, QTc >5ms potential side effects QTc (like amio) bradycardia creatinine*

12 1237 pts Paroxysmal AF Immediately post cardioversion (electrical, pharma, or spontaneous) Dronedarone vs. Placebo 12 mo Cumulative Incidence First Recurrence of AF.8 HR =.75 (p<.1) Placebo Dronedarone Time (days) 4628 pts Paroxysmal or Persistent AF/Flutter Age 7 + 1RF or Age 75 (HTN, DM, CVA/TIA, LA, EF<4%) Dronedarone vs. Placebo 12 mo ~85% HTN 6% structural heart disease only 6% lone AF ~⅓ previously CV d 7% on BB 14% on CCB 14% on Digoxin 7% on ACEi/ARB ~4% on statins

13 Primary outcome Combined endpoint of CV hospitalization and death from any cause Cumulative Incidence (%) CV Hospitalization or Death HR =.76 (p<.1) Placebo Dronedarone Months 7.5 CV Death HR =.71 (p<.3) 5 Stroke (post-hoc analysis) HR =.66 (p<.27) Cumulative Incidence (%) Placebo Dronedarone Months Cumulative Incidence (%) Placebo Dronedarone Months

14 cumulative incidence "An Update in Atrial Fibrillation Management" DIONYSOS 54 pts; Persistent AF undergoing CV Age 7 + 1RF or Age 75 not published (HTN, DM, CVA/TIA, LA, EF<4%) Dronedarone vs. Amiodarone 6 mo DIONYSOS Primary outcome recurrence of AF or premature discontinuation for intolerance or lack of efficacy Recurrence of AF or Discontinuation Dronedarone Amiodarone months DIONYSOS recurrences of AF with dronedarone (64% vs. 42%) intolerances with amiodarone (18% vs. 13%) discontinuation with dronedarone for lack of efficacy (21% vs. 6%)

15 stroke prevention symptom relief heart rate control ⅓ rate-related cardiomyopathy when the HR > 12 calcium channel blockers β-blockers digoxin 174 pts with permanent AF 6 month study of rate control RCT of dronedarone vs. placebo on top of standard Tx No adverse effects No pro-arrhythmia slight creatinine

16 -1-2 Mean HR on 24 hr Holter All patients + BB + Digoxin + CCB Dronedarone is a very good first line AAD in AF for both rate & rhythm control All-Cause Mortality or Hospitalization.8 HR = 1.38 (p=.12) 627 pts NYHA II-IV 1 episode of III-IV in last month EF~ 35% Dronedarone vs. Placebo 12 mo Cumulative Incidence Dronedarone Placebo Time (days)

17 .8 All-Cause Mortality HR = 2.13 (p<.3) Cumulative Incidence Dronedarone Placebo Dronedarone needs to be avoided in NYHA III/IV HF Time (days) Monthly costs $141 Monthly costs $141 $35 $5 $56 $5 $5 $71 $15 βb $15 βb Flecainide Amiodarone Propafenone Dronedarone Flecainide Amiodarone Propafenone Dronedarone 5mg bid 2mg OD 3mg bid 4mg bid 5mg bid 2mg OD 3mg bid 4mg bid

18 Monthly costs $141 $112 $91 $5 EP $56 CCB $56 CCB Flecainide Amiodarone Propafenone Dronedarone 5mg bid 2mg OD 3mg bid 4mg bid open for business Atrial Fibrillation Ablation

19 AAD vs. Ablation (highly Sx; failed 1 AAD) study 1 study 2 study 3 Overall favours AAD favours Ablation AF Ablation is a successful treatment alternative in the right AF patient Pleiotropic Drugs ACEi ARB statins

20 A Summary If CHADS2 >1, warfarin is better than ASA & Plavix If CHADS2 >1, and I can t use warfarin, ASA & Plavix is better than ASA alone (as long as they aren t bleeders!)

21 Watch very carefully when pts are on triple therapy Dabigatran is a very promising alternative to Warfarin in AF Dronedarone is a very good first line AAD in AF for both rate & rhythm control Dronedarone needs to be avoided in NYHA III/IV HF

22 AF Ablation is a successful treatment alternative in the right AF patient Before I came here I was confused about this subject. Having listened to your lecture, I am still confused. But on a higher level. - Enrico Fermi

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