Disclosures. Objectives. Management of Anticoagulation in The Patient with Atrial Fibrillation 4/3/2018

Transcription

1 Management of Anticoagulation in The Patient with Atrial Fibrillation Christopher A. Webber MSN, APRN-CNP Oklahoma Heart Institute Cardiac Electrophysiology Tulsa, Oklahoma Disclosures I have no actual or potential conflicts of interest in relation to this program/presentation Objectives Understand basic concepts of atrial fibrillation pathophysiology Discuss the basic pharmacology of common oral anticoagulants Identify the clinical indication for anticoagulation in patients at risk for stroke Review appropriate renal dosing 1

2 Atrial Fibrillation Prevalence increases with age Almost ¼ population will develop after age 40 Occurs along with multiple chronic diseases. Associated with a significant increase of stroke risk, heart failure, dementia, and mortality. Symptoms vary from minimal to debilitating (January, 2014) Pop Quiz! Which of the following is not associated with increased risk of developing AF? A. Hypertension B. Obesity C. Sleep Apnea D. Alcohol E. None of the above 2

3 Pathophysiology Definition: Supraventricular tachyarrhythmia with uncoordinated atrial activation and consequently ineffective atrial contraction. EKG findings Irregularly irregular R-R interval No P waves Irregular atrial activity Atrial clot formation Low flow Ineffective contractions lead to fibrosis Most often occurs in the left atrial appendage (January, 2014) What is this rhythm? 3

4 Thromboembolic Risk Class I AHA/ACC/HRS Guidelines for anticoagulation Individualized shared decision making based on risks/benefits Independent of type of AF (paroxysmal, persistent, or permanent) CHA 2 DS 2 -VASc greater than 2 Warfarin for mechanical heart valves and concurrent AF Warfarin, dabigatran, rivaroxaban, or apixaban for non-valvular AF without mechanical valve Monitor INR weekly initially and then monthly on warfarin If unable to maintain therapeutic INR on warfarin then try DOAC Evaluate renal function prior to and during therapy Same risk profile for AFL anticoagulation (January, 2014) Stroke Risk Calculation CHA 2 DS 2 VASc Score Risk Factor Score CHF or LVEF < 40% 1 Hypertension 1 Age > 75 2 Diabetes 1 Previous Stroke or TIA 2 Vascular Disease 1 Age Female Gender 1 Pop Quiz! 80 YO female with hypertension, CAD, CHF, prior CVA, diabetes and persistent AF CHADSVASC score 9 Yearly stroke risk is 12.2% YES! 4

5 Pop Quiz! 50 YO female with hypertension, paroxysmal atrial fibrillation (PAF) and mitral stenosis. CHADSVASC score 2 Yearly stroke risk is 2.2% per year YES! Risk of stroke with Mitral Stenosis 20x higher Bleeding risk HAS-BLED Score 3 is high risk! Hypertension SBP > 160 Abnormal Liver/Renal Function Stroke Bleeding history Labile INR Elderly Age > 65 Drugs/Alcohol use (Pisters, 2010) 5

6 Anticoagulation options Heparin infusion Low molecular weight heparin Enoxaparin/Lovenox Vitamin K antagonists Warfarin /Coumadin Direct thrombin inhibitor Dabigatran Factor Xa inhibitors Apixaban/Eliquis, edoxaban/savaysa, and rivaroxaban/xarelto (Brenner, 2013) Unfractionated Heparin Pharmacology of Unfractionated Heparin (UFH) Reversibly binds to thrombin and activated factor Xa Short half life (T ½)-1.5 hours Excreted through the urine Monitored clinically with the APTT, ACT, and Anti-Xa Requires frequent lab studies (Hirsh, et al., 2001) 6

7 Unfractionated Heparin Advantages Fast onset of action, reversibility, and ease of clinical monitoring Disadvantages/Risks High degree of patient to patient variability Hemorrhage, HIT, anaphylaxis, thrombocytopenia, and osteoporosis Use only suitable for acute care settings (Hirsh, et al., 2001) Low Molecular Weight Heparin Pharmacology Primarily inhibits factor X Only for parenteral administration Peak concentration 3-5 hours Metabolized in liver and CYP450 Urinary excretion (Brenner, 2013) Enoxaparin Dosing Dosing for DVT prophylaxis, BMI <40 40 mg SC daily Dosing for AF/AFL with normal renal function 1 mg/kg SC every 12 hours Dosing for AF/AFL with CrCl <30 1 mg/kg SC daily (Brenner, 2013) 7

8 Low Molecular Weight Heparin Laboratory monitoring CBC and BMP PTT does not need to be followed Adverse Effects Bleeding HIT Hyperkalemia (Brenner, 2013) Vitamin K Antagonists Warfarin (Coumadin) Pharmacology Inhibits factor II, VII, IX, and X Also inhibits protein C & S synthesis Inhibits multiple clotting factors Half life between 6-50 hours Excreted minimally unchanged in urine Metabolized in liver CYP450:1A2, 2C8, 2C18, and 2C9 pathway Multiple interactions (Brenner, 2013) Vitamin K Antagonists Dosing Consider genetic testing 2-5 mg daily with goal INR of 2-3 for AF Consider 10 mg daily x 2 days if healthy Should bridge during start, restart, or change of therapy Typically LMWH or UFH Frequently monitor INR as outpatient (Brenner, 2013) 8

9 Vitamin K Antagonists Key points New patients should get teaching Interaction with foods and multiple drugs Complex dosing and monitoring Must be used with mechanical valves Read the guidelines (Brenner, 2013) Dabigatran (Pradaxa) Pharmacology Directly binds to thrombin (factor II) Half life hours Metabolized in liver; CYP % Excreted in urine Dosing 150 mg PO BID CrCl 15-30: 75 mg PO BID (Connolly, 2009) Dabigatran (Pradaxa) Study design and summary FDA approval in 2010 after RE-LY trial 18,113 patients enrolled, CHADS 2 of 2.1 Superior to warfarin for stroke reduction 95% CI and P< Hemorrhagic CVA 0.38%/yr in warfarin and 0.1%/yr with dabigatran (Connolly, 2009) 9

10 Dabigatran (Pradaxa) Laboratory monitoring CBC, BMP, Pt/INR before start BMP every 6 months Adverse Effects Major bleeding events Hemorrhagic stroke Dyspepsia (Connolly, 2009) Dabigatran (Pradaxa) Transition from warfarin Stop warfarin Start dabigatran when INR < 2 Transition from other DOACs Stop other DOAC Start dabigatran at the next dose Transition from parenteral agent DC Parenteral Start DOAC 0-2 hrs before next dose (Connolly, 2009) Factor Xa Inhibitors Rivaroxaban, apixaban, and edoxaban Rivaroxaban approved in 2011, Rocket-AF trial Apixaban approved in 2012, ARISTOTLE trial Edoxaban approved in 2015, ENGAGE-AF TIMI trial 10

11 Rivaroxaban (Xarelto) Pharmacology Directly binds to Factor Xa Half life 5-9 hours Metabolized in liver; CYP450 2J2, substrate 3A4/5 66% Excreted in urine, 28% in feces Dosing 20 mg PO daily with evening meal CrCl 30-49: 15 mg PO daily (Patel, 2011) Rivaroxaban (Xarelto) Study design and summary 14,264 patients enrolled, CHADS 2 of 3.48 Noninferior to warfarin for stroke reduction 2.2%/yr with warfarin and 1.7% with rivaroxaban, 95% CI and P< Major and non-major clinical bleeding 1475 (14.9%/yr) and 1449 (14.5%/yr) (Patel, 2011) Rivaroxaban (Xarelto) Intracranial hemorrhage 0.5% vs 0.7% P=0.02 Fatal Bleeding 0.2% vs 0.5% P=0.003 Rivaroxaban is noninferior to warfarin for stroke risk reduction. Similar bleeding risk, and fewer ICH (Patel, 2011) 11

12 Apixaban (Eliquis) Pharmacology Directly binds to Factor Xa Half life: 12 hours Metabolized CYP450: 1A2, 2C8, 2C9, 2C19, 3A4 27% excreted in the urine Dosing 5 mg PO BID or 2.5 mg PO BID if ⅔ of the following apply Age > 80, Wt < 60 kg, or Cr > 1.5 (Granger, 2011) Apixaban (Eliquis) Study design and summary Over 18,000, CHADS score of % vs 1.60% stroke risk, P=<0.001 Hemorrhagic CVA 49% lower in apixaban group Warfarin group INR was in range 66% of time Lower CVA, bleeding, and mortality risk with Apixaban (Granger, 2011) Edoxaban (Savaysa) Pharmacology Directly binds to Factor Xa Half life: hours Metabolized CYP450: 3A4 substrate 50% excreted in the urine Dosing 60 mg PO daily with CrCl mg/min Avoid use is CrCl is > 95 mg/min 30 mg PO daily with CrCl mg/min (Ruff, 2010) 12

13 Edoxaban (Savaysa) Interacts with potent P-glycoprotein inhibitors Transition from warfarin Stop warfarin, start edoxaban when INR < 2.5 Transition from UFH Stop heparin, start edoxaban 4 hr later LMWH and DOAC Stop then start edoxaban at next scheduled dose (Ruff, 2010) Edoxaban (Savaysa) Study design and summary Over 21,000, 77% CHADS score <3 1.18% vs 1.5% stroke risk, P=<0.001 Annual bleeding risk 2.75% and 3.43% Warfarin group INR was in range 68% of time Hemorrhagic CVA 0.47% vs 0.26% (Ruff, 2010) Periop Considerations Not all procedures require holding DOAC Hold for 1-4 days based on CrCl, type, and bleeding risk Bridging is not routinely recommended No evidence to reduce thromboembolism risk Increased risk of bleeding Resume between hours post op (Bell, 2014) 13

14 Periop Considerations (Dubois, 2017) Left Atrial Appendage Exclusion Surgical options Atriclip: stroke risk reduction of 87.5% with atriclip Percutaneous options Watchman Amulet Lariat (Caliskan et al., 2017) 14

15 Left Atrial Appendage Exclusion Atriclip Left Atrial Appendage Exclusion Boston Scientific Watchman Left Atrial Appendage Exclusion St. Jude Medical Amulet 15

16 Left Atrial Appendage Exclusion Lariat DOAC Rapid Fire 60 year old woman with HTN and DMII. Palps, DOE, and orthopnea. Weighs 58 kg What is the rhythm? What is her CHADS VASC score? If CrCl > 50 then what dose of rivaroxaban would we use? Rivaroxaban dosing: 20 mg PO daily with evening meal unless CrCl is then 15 mg PO daily. If Cr is 1.4 then what dose of apixaban should we use? DOAC Rapid Fire 80 year old woman with HTN and and prior CVA. No symptoms. Weights 90 kg What is the rhythm? What is her CHADS VASC score? Apixaban dosing: 5 mg PO BID unless 2 of the following 3 apply. Then 2.5 mg PO BID 1. Age greater than or equal to Weight <60 kg 3. Cr >

17 DOAC Rapid Fire 75 year old male with HTN and CAD. Weekly palps and exertional chest pain. What is the rhythm? What is his CHADS VASC score? Should we anticoagulate based on this EKG? What test to eval Palps? References Bell, B. R., Spyropoulos, A. C., & Douketis, J. D.Perioperative management of the direct oral anticoagulants. Hematology/Oncology Clinics, 30(5), /j.hoc Retrieved from Brenner, G. M., & Stevens, C. W. (2013). Pharmacology. Philadelphia, PA: Elsevier/Saunders. Connolly, S. J., Ezekowitz, M. D., Yusuf, S., Eikelboom, J., Oldgren, J., Parekh, A.,.. Wallentin, L. (2009). Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med, 361(12), /NEJMoa Dubois, V., Dincq, A., Douxfils, J., Ickx, B., Samama, C., DognÃ, J.,... Lessire, S. (2017). Perioperative management of patients on direct oral anticoagulants. Thrombosis Journal, 15(1), /s Retrieved from Etem Caliskan, Ayhan Sahin, Murat Yilmaz, Burkhardt Seifert, Ricarda Hinzpeter, Hatem Alkadhi, James L. Cox, Tomas Holubec, Diana Reser, Volkmar Falk, Jürg Grünenfelder, Michele Genoni, Francesco Maisano, Sacha P. Salzberg, Maximilian Y. Emmert; Epicardial left atrial appendage AtriClip occlusion reduces the incidence of stroke in patients with atrial fibrillation undergoing cardiac surgery, EP Europace,, eux211, 18 July 2017 Granger, C. B., Alexander, J. H., McMurray, J. J. V., Lopes, R. D., Hylek, E. M., Hanna, M.,... Wallentin, L. (2011). Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med, 365(11), /NEJMoa January, C. T., Wann, L. S., Alpert, J. S., Calkins, H., Cigarroa, J. E., Conti, J. B.,... & Sacco, R. L. (2014) AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology, 64(21), e1-e76. Ruff, C. T., Giugliano, R. P., Antman, E. M., Crugnale, S. E., Bocanegra, T., Mercuri, M.,... & McCabe, C. H. (2010). Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: Design and rationale for the Effective anticoagulation with factor xa next GEneration in Atrial Fibrillation Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF TIMI 48). American heart journal, 160(4), Patel, M. R., Mahaffey, K. W., Garg, J., Pan, G., Singer, D. E., Hacke, W.,... Califf, R. M. (2011). Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med, 365(10), /NEJMoa

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