Download Atrial Fibrillation

Practical Considerations in Atrial
Fibrillation
Christopher W. Kocher, MD
Department of Cardiology
Confluence Health
Atrial Fibrillation
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1% overall prevalence in the general population
3% incidence at age 60
9% incidence at age 80
Most common arrhythmia requiring hospital admission
Risk factors for Atrial Fibrillation
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Age
Gender
Ethnicity
Geography
Risk Factors for AF
Frequent PACs
Echocardiography
– Left atrial enlargement
– Increased LV wall thickness
– Reduced LV function (fractional shortening)
Risk Factors for AF
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Hypertension
CAD
Valvular Heart Disease (rheumatic)
CHF
HCM
Risk Factors for AF
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OSA
Venous thromboembolic disease
Obesity
Chronic kidney disease
Diabetes
Genetics of AF
• Framingham registry
– Increased risk with 1st degree relative
• Likely polygenic inheritance
• Some single gene mutations
– KCNQ1
– SCN5A
Other Causes of AF
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Hyperthyroidism
Alcohol
Inflammation
Birth Weight
Pericardial Fat
Cardiac surgery
Atrial Fibrillation in the post-op Period
Possible Associations with AF
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Low magnesium
Caffeine
Fish Oil
Bisphosphonates
Air Pollution
Exercise
Stroke
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Most concerning effect of AF
Mainly an embolic phenomenon
Risk is independent of AF duration
Individual risk is highly variable
Assessing Stroke Risk
Estimating Bleeding Risk
HAS-BLED
Agents for anticoagulation
• Warfarin (coumadin)
• Aspirin
• Novel Oral Anticoagulants (NOAC)
– Direct Thrombin inhibitors
– Factor Xa inhibitors
Warfarin
• Standard therapy for stroke prevention in AF
– Reduces incidence of stroke by 60-70%
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Vitamin K antagonist
Significant lag in onset/offset
Cheap
Requires monitoring
Has an antidote
Lots of food/drug interactions
Warfarin
Drug interactions
• Increase INR
– Amiodarone, acetaminophen,
allopurinol, antibiotics, azole
antifungals, gemfibrozil,
“statins”, cimetidine, PPI’s,
SSRIs, tramadol
• Decrease INR
– Nafcillin, rifampin, antiepileptics, St. John’s Wort
Food interactions
• High vitamin K
– Green leafy vegetables (kale,
spinach, brussel sprouts)
– Alcohol
Novel Oral Anticoagulants (NOAC)
• Direct thrombin inhibitors
– dabigatran
• Factor Xa inhibitors
– Rivaroxiban,apixiban,edoxiban
Coagulation Cascade
DOAC- General
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Do not require monitoring
Fewer drug and food interactions
Renal metabolism
Less intracranial hemorrhage
Not approved for use in pregnancy
Not approved for use with prosthetic heart
valves
Specific Agents
• Pradaxa
– GI upset
– BID dosing
– Only NOAC with an antidote (Prax-bind)
• Xarelto (rivaroxaban)
• Eliquis (apixiban)
– BID dosing
• Savaysa (edoxiban)
– Reduced efficacy with high GFR
Dabigatran
Re-LY (dabigatran trial)
Cumulative Hazard Rates for the Primary Outcome of Stroke or Systemic Embolism,
According to Treatment Group
Connolly SJ et al. N Engl J Med 2009;361:1139-1151
Safety Outcomes, According to Treatment Group
Re-LY (dabigatran trial)
Connolly SJ et al. N Engl J Med 2009;361:1139-1151
Discontinuation of the Study Drug, Adverse Events, and Liver Function According to
Treatment Group
Re-LY
(dabigatran trial)
Connolly SJ et al. N Engl J Med 2009;361:1139-1151
Dabigatran
Efficacy proven in the ROCKET –AF trial
Once daily dosing
Dose reduction for impaired renal function
Avoid with: dronedarone, cyclosporine,
itra/ketoconazole
Reduce dose with: amiodarone, verapamil
Dabigatran antidote
Rocket AF
Rates of Bleeding
Events.
ROCKET
AF
Patel MR et al. N Engl J Med 2011;365:883-891
Apixiban
Efficacy proven in the ARISTOTLE trial
Twice daily dosing
Dose reduction for impaired renal function
Edoxiban
Efficacy proven in the trial
Once daily dosing
Limited efficacy for GFR >95ml/min
NOAC-General
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No way to measure compliance
Primarily renal metabolism
Rapid onset of action
Interaction with certain drugs
– Strong P-gy and CYP 3A4 inhibitors
Drugs to Avoid
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Dronedarone
Clarithromycin
Itraconazole (systemic)
Verapamil
Amiodarone (weak CYP 34A inhibitor)
Aspirin for Stroke prevention
• Poorly studied
• Certainly inferior to systemic anticoagulation
• Meta-analysis suggests no real benefit in
reducing disabling stroke
• Swedish registry suggests INCREASED risk of
stroke and thromboembolic events
• Current guidelines suggest that NO therapy is
as acceptable as aspirin for low risk groups
Active A
Relative Risks of Hemorrhage, According to Treatment Group
10% RRR in stroke
60%
increased risk of bleeding
The ACTIVE Investigators. N Engl J Med 2009;360:20662078
Cumulative Incidence of Trial Outcomes, According to Treatment Group
Active A
10% RRR in stroke
The ACTIVE Investigators. N Engl J Med 2009;360:20662078
Role of the LAA in Stroke
Up to 90% of LA thrombi
are thought to originate in
the left atrial appendage
Left Atrial Appendage
Left Atrial Appendage
Non-medical Stroke Prophylaxis
• LAA occlusion
– Surgical
– Watchman
– Lariat
Watchman
Watchman
• Protect AF trial
– 700 patients randomized to device or warfarin
– Proven “non-inferior” to warfarin
• Approved for reducing stroke in patients with
AF
Watchman
• High initial complication rate
– Mostly pericardial effusions
• Still requires warfarin (45 days) and aspirin
and clopidogrel (6 months)
Watchman
• Prevail Trial
• Did not meet primary composite endpoint for
non-inferiority
– Very low event rate in the control group (warfarin)
• Did meet criteria for non-inferiority for
composite of ischemic stroke and systemic
embolism
• Significant reduction in complications vs.
PROTECT-AF trial (8.7%-4.2%)
Watchman
• Granted FDA approvalThe WATCHMAN Device
is indicated to reduce the risk of
thromboembolism from the left atrial
appendage in patients with non-valvular atrial
fibrillation who:
– Are at increased risk for stroke and systemic embolism based on
CHADS2 or CHA2DS2-VASc scores and are recommended for
anticoagulation therapy;
– Are deemed by their physicians to be suitable for warfarin; and
– Have an appropriate rationale to seek a non-pharmacologic
alternative to warfarin, taking into account the safety and
effectiveness of the device compared to warfarin.
Detection of Atrial Fibrillation
• Incidence of AF in setting of cryptogenic
stroke
• Use of ambulatory monitoring
• Implantable monitors
– LINQ
Medtronic Linq
REFRENCES
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Connolly SJ, Ezekowitz MD, Yusuf S, et al, “Dabigatran Versus Warfarin in Patients With Atrial Fibrillation,”
N Engl J Med, 2009, 361(12):1139-51
Patel MR, Mahaffey KW, Garg J, et al, “Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation,” N
Engl J Med, 2011, 365(10):883-91
Granger CB, Alexander JH, McMurray JJ, et al, "Apixaban versus Warfarin in Patients With Atrial
Fibrillation," N Engl J Med, 2011, 365(11):981-92
Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation
(ENGAGE AF-TIMI 48). N Engl J Med. 2013;369:2093-2104Top of Form
January CT, Wann LS, Alpert JS, et. al. 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. J Am Coll Cardiol. 2014 Dec 2;64(21):e1-e76
Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and
stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study.
Dewland TA, Olgin JE, Vittinghoff E, Marcus GM. Incident atrial fibrillation among Asians, Hispanics, blacks,
and whites. Circulation 2013; 128:2470
Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predicting hemorrhage: results from
the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151:713.
Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major
bleeding in outpatients treated with warfarin. Am J Med 1998; 105:91.
ACTIVE Writing Group of the ACTIVE Investigators, Connolly S, Pogue J, et al. Clopidogrel plus aspirin
versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for
prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367:1903.
ACTIVE Investigators, Connolly SJ, Pogue J, et al. Effect of clopidogrel added to aspirin in patients with
atrial fibrillation. N Engl J Med 2009; 360:2066.