Anticoagulation: How Do I Pick From All the Choices? Jeffrey H. Neuhauser, DO, FACC BHHI Primary Care Symposium February 28, 2014

Transcription

1 Anticoagulation: How Do I Pick From All the Choices? Jeffrey H. Neuhauser, DO, FACC BHHI Primary Care Symposium February 28, 2014

2 Atrial Fibrillation 2

3 Atrial Fibrillation The most common arrhythmia encountered in clinical practice. The prevalence increases with age. Risk factors include HPTN, valvular heart disease, cardiomyopathy, obesity, sleep apnea, congenital heart disease, pulmonary disease, & hyperthyroidism. Classified as paroxysmal, persistent, or permanent. Major complications include CHF & stroke. 3

4 LAA Thrombus 4

5 AF - CASE STUDIES 45 yr old male. No significant PMH. Develops AF while training for a marathon. He presents to the ER & then spontaneously converts to SR after 6 hrs. Baseline ECG & Echo are normal. 76 yr old female with HPTN, NIDDM who presents to her PCP for an annual checkup is found to be in AF with a controlled ventricular response. She is completely unaware that she is in AF. She has a history of GI hemorrhage within the past year. 68 yr old male with previous CABG, CHF, HPTN, & AS presents to the ER with a 2 day history of palpitations. He is found to be in AF with a RVR. He is admitted to the hospital & started on IV diltiazem for rate control. 5

6 CHADS2 Go AS, Hylek EM, Chang Y, et al. JAMA 2003; 290:2685 6

7 CHA2DS2-VASc Eur Heart J 2010; 31:2369 7

8 CHA2DS2-VASc Eur Heart J 2010; 31:2369 8

9 Warfarin Inhibits vit K dependent coagulation factors Metabolism - Liver CYP450 1/2 life 20-60h Dose adjusted to INR 2-3 Many drug & food interactions Common drugs that increase the INR - Quinolones, Erythromycins, Tetracyclines antifungals, Isoniazid, Amio, Propafenone, Gemfibrizol, Niacin,Pantoprozole, Paroxitene, Rouvastatin 9

10 Dabigatran (Pradaxa) Direct thrombin inhibitor Indicated for the prevention of stroke & thromboembolism in nonvalvular AF No liver CYP 450 metabolism; Primarily urine excretion 1/2 life hrs CrCl >50 ml/min - dose 150mg bid CrCl ml/min - dose 75 mg bid 10

11 Drugs that Increase Dabigatran Levels Cyclosporin Dronedarone Antifungal agents - Itraconazole & Ketoconazole Quinidine Verapamil 11

12 Drugs That Decrease Dabigatran Levels Carbamazepine Rifampin St. John s Wort 12

13 RE-LY Comparison of Dabigatran (150 mg bid & 110 mg bid) with warfarin in pts with nonvalvular AF & risk of stroke. Randomized, blinded for dabigatran, unblinded for warfarin Primary outcome was stroke or systemic embolization Median duration of F/U - 2 years N Engl J Med 2009; 361:

14 RE-LY Efficacy outcomes according to treatment group N Engl J Med 2009; 361:

15 RE-LY Cumulative hazard rates for stroke or systemic embolization according to treatment group. N Engl J Med 2009; 361:

16 RE-LY Safety outcomes N Engl J Med 2009; 361:

17 Concomittant Use of Antiplatelet in the RE-LY Trial Circulation. 2013;127:

18 Periprocedural Bleeding in the RE-LY Trial Circulation. 2012;126:

19 Periprocedural Bleeding in the RE-LY Trial Circulation. 2012;126:

20 RE-ALIGN Dabigatran vs warfarin S/P AVR & MVR within 7 days & after 3 months. Dabigatran dose 150, 220, 300mg bid based on renal function. The trial was terminated prematurely due to an excess of thromboembolic & bleeding events in the dabigatran group. N Engl J Med 2013;369:

21 Rivaroxaban (Xarelto) Factor Xa inhibitor Indicated for the prevention of stroke & thromboembolism in nonvalvular AF. Also indicated for the prevention & tx of DVT/PE. Metabolism - Liver CYP450; Urinary excretion 66% 1/2 life 5-9 hrs; hrs in the elderly CrCl >50 ml/min - dose 20 mg daily CrCl ml/min - dose 15 mg daily 21

22 Drugs That Increase Rivaroxaban Levels Amiodarone, Dronedarone Erythromycins Cyclosporine Diltiazem Antifungal agents - Itraconazole & Ketoconazole Phenytoin Ranolazine Tamoxifen Verapamil 22

23 Drugs That Decrease Rivaroxaban Levels Carbamazepine Phenytoin Rifampin St. John s Wort 23

24 ROCKET AF Comparison of Rivaroxaban (20 mg daily) vs warfarin (INR 2-3) in pts with nonvalvular AF. Randomized, double blind design. Primary endpoint - stroke or systemic embolization. N Engl J Med 2011;365:

25 ROCKET AF The Rivaroxaban group had 21% reduction in stroke & systemic embolization. Incidence of major bleeding was similar - Rivaroxaban (14.9%) vs warfarin (14.5%). The Rivaroxaban group had significantly less intracranial hemorrhage (0.5% vs 0.7%) & fatal hemorrhage (0.2% vs 0.5%). N Engl J Med 2011;365:

26 ROCKET AF N Engl J Med 2011;365:

27 ROCKET AF N Engl J Med 2011;365:

28 ROCKET AF J Am Coll Cardiol 2013;61:

29 ROCKET AF The mean time in therapeutic range in the warfarin group was 55.2%. The mean time with an INR <2 was 29.1%. The mean time with an INR >3 was 15.7%. J Am Heart Assoc. 2013;2:e doi /JAHA

30 Apixaban (Eliquis) Factor Xa inhibitor Indicated for the prevention of stroke & thromboembolism in nonvalvular AF Metabolism - Liver CYP450; Urine excretion 27% 1/2 life 12 hrs Dose 5 mg bid Creat >1.5, age >80, wt <60 kg - dose 2.5 mg bid 30

31 Drugs That Decrease Apixaban Levels Dexamethasone Nafcillin Phenobarbital Phenytoin Rifampin St. John s Wort 31

32 ARISTOTLE Apixaban vs Warfarin in pts with AF Randomized, double blind trial design Pts had at least 1 additional RF for stroke Primary outcome: stroke or systemic embolization Median duration of F/U years 32

33 ARISTOTLE N Engl J Med 2011;365:

34 ARISTOTLE N Engl J Med 2011;365:

35 AVERROES Apixaban vs ASA in pts with AF Double blind, randomized design Mean F/U 1.1 years The primary outcome was stroke or systemic embolization N Engl J Med 2011;364:

36 AVERROES N Engl J Med 2011;364:

37 AVERROES N Engl J Med 2011;364:

38 LAA Occlusion Devices 38

39 PROTECT AF Comparison of a LAA closure device (Watchman) with warfarin for the prevention of stroke & systemic embolization in pts with nonvalvular AF & at least 1 risk factor. After device implantation, pts received warfarin for 45 days, followed by clopidogrel for 4.5 months & then life long ASA. Mean F/U 2.3 yrs. Composite endpoint - stroke, systemic embolization, & CV death. Primary composite endpoint in the Watchman group (3%) was equivalent to the warfarin group (4.3%). Circulation.2013;127:

40 PROTECT AF Circulation.2013;127:

41 ASAP Study Evaluation of the Watchman LAA closure device in pts with nonvalvular AF ineligible for warfarin. 150 pts with nonvalvular AF & CHADS2 score at least 1 Primary efficacy end point was the combined events of ischemic stroke, hemorrhagic stroke, systemic embolization, CV / unexplained death. J Am Coll Cardiol 2013;61:

42 ASAP Study Pts with LVEF <30%, intracardiac thrombus, dense spontaneous echo contrast on TEE, PFO, significant mitral stenosis, pericardial effusion >3 mm, mobile plaque in the ascending aorta or aortic arch were excluded. Following implant, pts received 6 months of clopidogrel or ticlopidine followed by life long ASA. The mean CHADS2 score was 2.8. Mean f/u 14.4 months. J Am Coll Cardiol 2013;61:

43 ASAP Study The expected rate of ischemic stroke for pts treated only with ASA was 7.3%. J Am Coll Cardiol 2013;61:

44 THE WATCHMAN LAA OCCLUSION DEVICE 44

45 Cryoablation for AF 45