Embed Size (px)
Citation preview
4/3/2018
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
4/3/2018
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
4/3/2018
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?
4/3/2018
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)
– CHA2DS2-VASc greater than 2
– Warfarin for mechanical heart valves and concurrent AF
– Warfarin, dabigatran, rivaroxaban, or apixaban for non-valvular AFwithout mechanical valve
– Monitor INR weekly initially and then monthly on warfarin
– If unable to maintain therapeutic INR on warfarin thentry DOAC
– Evaluate renal function prior to and during therapy
– Same risk profile for AFL anticoagulation
(January, 2014)
Stroke Risk Calculation• CHA2DS2VASc 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 65-74 1
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!
4/3/2018
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)
4/3/2018
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)
4/3/2018
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)
4/3/2018
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)
4/3/2018
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 12-17 hours
– Metabolized in liver; CYP450
– 80 % 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, CHADS2 of 2.1
– Superior to warfarin for stroke reduction
• 95% CI and P< 0.001
– Hemorrhagic CVA
• 0.38%/yr in warfarin and 0.1%/yr with dabigatran
(Connolly, 2009)
4/3/2018
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
4/3/2018
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, CHADS2 of 3.48
– Noninferior to warfarin for stroke reduction
• 2.2%/yr with warfarin and 1.7% with rivaroxaban, 95% CI and P< 0.001
– 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)
4/3/2018
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 2
– 1.27% 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: 10-14 hours
– Metabolized CYP450: 3A4 substrate
– 50% excreted in the urine
• Dosing– 60 mg PO daily with CrCl 50-95 mg/min
– Avoid use is CrCl is > 95 mg/min
– 30 mg PO daily with CrCl 15-50 mg/min(Ruff, 2010)
4/3/2018
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 24-72 hours post op
(Bell, 2014)
4/3/2018
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)
4/3/2018
15
Left Atrial Appendage Exclusion
• Atriclip
Left Atrial Appendage Exclusion
• Boston Scientific Watchman
Left Atrial Appendage Exclusion
• St. Jude Medical Amulet
4/3/2018
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 15-50 then 15 mg PO daily.
DOAC Rapid Fire80 year old woman with HTN and and prior CVA. No symptoms. Weights 90 kg
What is the rhythm?
What is her CHADS VASC score?
If Cr is 1.4 then what dose of apixaban should we use?
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 802. Weight <60 kg3. Cr > 1.5
4/3/2018
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 anticoagulatebased on this EKG?
What test to eval Palps?
ReferencesBell, B. R., Spyropoulos, A. C., & Douketis, J. D.Perioperative management of the direct oral anticoagulants. Hematology/Oncology Clinics, 30(5), 1073-1084. 10.1016/j.hoc.2016.05.005 Retrieved from http://dx.doi.org/10.1016/j.hoc.2016.05.005
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), 1139-1151. 10.1056/NEJMoa0905561
Dubois, V., Dincq, A., Douxfils, J., Ickx, B., Samama, C., Dogné, J., . . . Lessire, S. (2017). Perioperative management of patients on direct oral anticoagulants. Thrombosis Journal, 15(1), 14. 10.1186/s12959-017-0137-1 Retrieved from https://doi.org/10.1186/s12959-017-0137-1
Etem Caliskan, Ayhan Sahin, Murat Yilmaz, Burkhardt Seifert, Ricarda Hinzpeter, Hatem Alkadhi, James L. Cox, Tomas Holubec, Diana Reser, VolkmarFalk, 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, https://doi.org/10.1093/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), 981-992. 10.1056/NEJMoa1107039
January, C. T., Wann, L. S., Alpert, J. S., Calkins, H., Cigarroa, J. E., Conti, J. B., ... & Sacco, R. L. (2014). 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 Xainhibitor 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), 635-641.
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), 883-891. 10.1056/NEJMoa1009638
4/3/2018
18
